Hematology Reports

12 pages, 819 KB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Anticoagulation Stability in Critically Ill Patients Receiving Argatroban for Suspected or Confirmed Heparin-Induced Thrombocytopenia Compared with Unfractionated Heparin: A Retrospective Cohort Study

by Imran Khan, Elizabeth Lamarche, Bernadett Kovacs, Ariel Hendin, Andy Pan, Caitlin Richler, Christine Landry, Sydney Morin, Kaouther Derouiche and Pierre Thabet

Hematol. Rep. 2026, 18(3), 31; https://doi.org/10.3390/hematolrep18030031 - 30 Apr 2026

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Abstract

Background: Achieving and maintaining therapeutic anticoagulation with unfractionated heparin in critically ill patients is challenging due to biologic variability, heparin resistance, and limitations of activated partial thromboplastin time (aPTT) monitoring. Argatroban, a direct thrombin inhibitor, provides antithrombin-independent anticoagulation with more predictable pharmacokinetics, but [...] Read more.

Background: Achieving and maintaining therapeutic anticoagulation with unfractionated heparin in critically ill patients is challenging due to biologic variability, heparin resistance, and limitations of activated partial thromboplastin time (aPTT) monitoring. Argatroban, a direct thrombin inhibitor, provides antithrombin-independent anticoagulation with more predictable pharmacokinetics, but real-world data describing its anticoagulation stability in the intensive care unit (ICU) remain limited. Objective: This study aimed to compare anticoagulation stability between continuous intravenous argatroban and unfractionated heparin in critically ill patients using time in therapeutic range (TTR) based on aPTT as the primary performance metric. Methods: A retrospective cohort study was conducted in the ICU and step-down unit of Hôpital Montfort (Ottawa, ON, Canada) between January 2016 and December 2024. Adult patients receiving continuous intravenous argatroban or unfractionated heparin for systemic anticoagulation were included. All aPTT values obtained during active infusion were extracted, and TTR was calculated using linear interpolation between consecutive measurements. Continuous variables were summarized as medians with interquartile ranges and compared using the Wilcoxon rank-sum test; categorical TTR strata were compared using Fisher’s exact test. Results: Sixty-eight patients met the inclusion criteria, contributing 9 argatroban and 61 heparin infusion courses. Argatroban demonstrated a higher median TTR than heparin (83.3% [IQR 82.0–90.7] vs. 47.5% [32.9–62.4]; p < 0.001), with a moderate-to-large effect size (r = 0.51). Median aPTT values were similar between groups, but argatroban showed narrower dispersion and fewer prolonged subtherapeutic periods. A majority of heparin courses (56.5%) spent <50% of time within range, whereas no argatroban courses fell into this category. Conversely, 33.3% of argatroban courses achieved ≥90% TTR compared with none in the heparin group. Conclusions: In this real-world ICU cohort where argatroban was used for suspected or confirmed HIT, argatroban was associated with higher TTR than unfractionated heparin. These findings support the use of time-dependent metrics to evaluate anticoagulation quality and warrant prospective studies in more homogeneous populations. Full article

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16 pages, 1210 KB

Open AccessEditor’s ChoiceReview

VEXAS Syndrome: Clinical Features, Hematologic Involvement, and Clinical Outcomes of Current and Emerging Therapies

by Chanika Assavarittirong, Christopher Grant, Sandeep S. Nayak and Anthony L. Nguyen

Hematol. Rep. 2026, 18(3), 30; https://doi.org/10.3390/hematolrep18030030 - 23 Apr 2026

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Abstract

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet’s syndrome, relapsing [...] Read more.

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet’s syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included “VEXAS” and “treatment.” Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-α inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome. Full article

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15 pages, 1874 KB

Open AccessEditor’s ChoiceArticle

The Prognostic Value of the CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) Ratio for Leukemic Transformation in MDS

by Panagiotis Panagiotidis, Emmanuel Karavanis, Konstantinos Neanidis, Eleftherios Panteris and Maria Moysidou

Hematol. Rep. 2026, 18(2), 29; https://doi.org/10.3390/hematolrep18020029 - 15 Apr 2026

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Abstract

Background/Objectives: Myelodysplastic syndromes (MDS) are associated with a significant risk of progression to acute myeloid leukemia (AML), affecting approximately 30% of patients. In high-risk MDS, leukemic transformation may occur within a short time frame, highlighting the need for early and reliable biomarkers of [...] Read more.

Background/Objectives: Myelodysplastic syndromes (MDS) are associated with a significant risk of progression to acute myeloid leukemia (AML), affecting approximately 30% of patients. In high-risk MDS, leukemic transformation may occur within a short time frame, highlighting the need for early and reliable biomarkers of disease progression. Increasing evidence suggests that immune dysregulation and cytotoxic T-cell dysfunction contribute to disease evolution. This study aimed to evaluate PD-1 and CD57 expressions on CD8⁺ T cells and to investigate the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio (PERLS) as a potential immunological marker predictive of leukemic transformation. Methods: Thirty-one patients with MDS were prospectively followed over a 12-month period. At baseline, patients underwent routine clinical and laboratory evaluation, including multiparameter flow cytometric assessment of bone marrow blasts. An extended immunophenotypic analysis of bone marrow samples was performed at study entry to assess PD-1 and CD57 expression on CD8⁺ T cells. Cytogenetic and molecular analyses were conducted when clinical findings suggested disease progression. Patients who developed signs of progression were re-evaluated approximately one month later, during the progression phase, to assess dynamic immunological changes. Results: Of the thirty-one patients included, eighteen progressed to AML, whereas thirteen remained clinically stable. Patients who progressed demonstrated a significant increase in PD-1 and CD57 expression on CD8⁺ T cells compared with stable patients. Moreover, a markedly higher CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) ratio was observed in patients who subsequently developed AML, particularly during the progression phase. Conclusions: Dynamic immunophenotypic monitoring reveals that increased PD-1 on CD8⁺ T cells and an elevated PERLS ratio are associated with imminent leukemic transformation in MDS. These findings support the incorporation of immune-based biomarkers, particularly the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio, into routine risk assessment to enable earlier identification of disease progression and timely therapeutic intervention. Full article

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19 pages, 2966 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Metabolomic Signatures of Relapse and Survival in AML Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

by Igor Novitzky-Basso, Changjiang Xu, Caden Chiarello, Julie A. Reisz, Angelo D’Alessandro, Gary D. Bader, Jonas Mattsson and Courtney Jones

Hematol. Rep. 2026, 18(2), 27; https://doi.org/10.3390/hematolrep18020027 - 7 Apr 2026

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Abstract

Objectives: Allogeneic stem cell transplantation (HSCT) is curative in acute myeloid leukemia (AML) but is limited by relapse and non-relapse mortality (NRM). Metabolomic prognostic value is unclear. We assessed whether plasma metabolite profiles at diagnosis, pre-transplant, and post-transplant are associated with overall [...] Read more.

Objectives: Allogeneic stem cell transplantation (HSCT) is curative in acute myeloid leukemia (AML) but is limited by relapse and non-relapse mortality (NRM). Metabolomic prognostic value is unclear. We assessed whether plasma metabolite profiles at diagnosis, pre-transplant, and post-transplant are associated with overall survival (OS) and cause-specific mortality. Methods: We retrospectively analyzed plasma metabolites from 63 AML patients undergoing HSCT (263 samples). Results: Higher levels of valine (hazard ratio [HR] 24.454), citrulline (HR 20.478), 5-oxoproline (HR 11.766), and glutamine (HR 8.701) associated with higher NRM, while inosine diphosphate (HR 0.091) and pyridoxamine-5′-phosphate (HR 0.313) associated with lower NRM. For relapse-related mortality (RRM), higher levels of phenylalanine (HR 26.585), leucine/isoleucine (HR 10.755), indolepyruvate (HR 7.676), and creatinine (HR 13.874) were associated with higher RRM, while trans-4-hydroxy-L-proline (HR 0.101) was associated with lower RRM. Higher post-transplant ornithine (HR 0.063), 3-sulfocatechol (HR 0.590), and indole-3-acetate (HR 0.359) were associated with improved OS. Mixed-effects modelling identified lower dehydroascorbate and citrate in relapsed patients, with dehydroascorbate remaining significant after false discovery rate adjustment. Conclusions: Metabolomic profiling nominated candidate metabolites for validation in larger prospective studies and elucidated mechanistic pathways, potentially informing novel interventions or risk-adapted monitoring strategies in HSCT. Full article

(This article belongs to the Special Issue Outcomes and Complications Post-Allogeneic Hematopoietic Cell Transplantation)

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16 pages, 279 KB

Open AccessEditor’s ChoiceReview

Pediatric Oral Iron Therapy: Choosing the Right Product for Your Patient

by Sonia Alexiadou, Emmanouela Tsouvala and Elpis Mantadakis

Hematol. Rep. 2026, 18(2), 20; https://doi.org/10.3390/hematolrep18020020 - 5 Mar 2026

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Abstract

In this narrative review, we address the prevention and therapy of iron deficiency anemia (IDA) with oral iron products in pediatric patients. Fortification of complementary foods with iron-containing micronutrient powders is the preferred method for the prevention of IDA in resource-limited settings. In [...] Read more.

In this narrative review, we address the prevention and therapy of iron deficiency anemia (IDA) with oral iron products in pediatric patients. Fortification of complementary foods with iron-containing micronutrient powders is the preferred method for the prevention of IDA in resource-limited settings. In developed countries, the prevention of sideropenia is through the consumption of iron-rich foods of animal origin. Regarding oral iron therapy, ferrous sulfate is the most widely used and cheapest product, but it is less well tolerated due to gastrointestinal side effects compared to complexes of ferric iron with polysaccharides, and complexes of iron with amino acids in casein, such as iron protein succinylate and iron acetyl aspartylate. These latter products are expensive and available only as single-dose vials with a fixed amount of elemental iron. Intermittent administration of ferrous sulfate, once or twice a week, is equally effective to daily therapy, with fewer side effects, and can be used in selected patients. Oral carbonyl iron has excellent bioavailability and the additional advantage of a high safety margin in cases of accidental overdose compared to iron salts, an important consideration given the potentially lethal consequences of iron overdose. Newer liposomal and sucrosomial iron products appear to have better intestinal tolerance and similar efficacy in the treatment of IDA, but limited pediatric data exist. In conclusion, all oral medicinal iron products are effective when prescribed for the treatment of IDA, if well-absorbed and taken consistently for 3 to 6 months. Physicians should be prepared to use alternative oral agents with better tolerance in case of gastrointestinal side effects. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

14 pages, 706 KB

Open AccessEditor’s ChoiceReview

Inherited Platelet Disorders During Pregnancy and Delivery: Overview of Management Strategies and Emerging Therapeutic Considerations

by Victor Zibara and Nicoletta Machin

Hematol. Rep. 2026, 18(2), 16; https://doi.org/10.3390/hematolrep18020016 - 26 Feb 2026

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Abstract

Inherited platelet disorders (IPDs) comprise a heterogeneous group of rare conditions that present particular challenges during pregnancy, with bleeding risk increasing during labor and the immediate postpartum period. These disorders require coordinated, multidisciplinary management to mitigate maternal and neonatal bleeding risk. Although data [...] Read more.

Inherited platelet disorders (IPDs) comprise a heterogeneous group of rare conditions that present particular challenges during pregnancy, with bleeding risk increasing during labor and the immediate postpartum period. These disorders require coordinated, multidisciplinary management to mitigate maternal and neonatal bleeding risk. Although data remains limited, individuals with IPD, including Bernard–Soulier syndrome, Glanzmann thrombasthenia, MYH9-related disorders, Hermansky–Pudlak syndrome, and platelet storage pool disorders, are at an increased risk for obstetrical bleeding, with the degree of risk varying by underlying diagnosis. In severe inherited platelet disorders such as Glanzmann thrombasthenia, peripartum hemorrhage is common, with up to half of the deliveries in some series requiring red cell or platelet transfusion. Because these conditions are congenital, the fetus may also be affected, placing neonates at risk for serious bleeding complications, including intracranial hemorrhage, although available data is limited. Despite the considerable morbidity and mortality risk associated with inherited platelet disorders, management strategies during pregnancy and delivery remain poorly defined. This stands in contrast to other bleeding disorders, such as factor deficiencies, for which multiple therapeutic approaches have been evaluated in the peripartum setting. In this review, we summarize the available evidence and current management strategies for individuals with inherited platelet disorders during pregnancy and delivery. Full article

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10 pages, 463 KB

Open AccessEditor’s ChoiceReview

Factors Influencing the Use of G-CSF in Drug-Induced Agranulocytosis

by Emmanuel Andrès, Jean-Edouard Terrade, Xavier Jannot and Noel Lorenzo-Villalba

Hematol. Rep. 2026, 18(1), 14; https://doi.org/10.3390/hematolrep18010014 - 3 Feb 2026

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Abstract

Drug-induced agranulocytosis is a rare but life-threatening adverse reaction associated with numerous non-chemotherapy drugs. Management relies on immediate drug withdrawal, infection control, and, in selected patients, administration of granulocyte-colony stimulating factor (G-CSF). This review summarizes current knowledge on the determinants of epidemiology, clinical [...] Read more.

Drug-induced agranulocytosis is a rare but life-threatening adverse reaction associated with numerous non-chemotherapy drugs. Management relies on immediate drug withdrawal, infection control, and, in selected patients, administration of granulocyte-colony stimulating factor (G-CSF). This review summarizes current knowledge on the determinants of epidemiology, clinical presentation, hematologic and biologic features, comorbidities, and outcomes influencing the decision to introduce G-CSF in drug-induced agranulocytosis. Evidence from observational studies and meta-analyses suggests that G-CSF shortens neutropenia duration and hospitalization, although its impact on mortality remains uncertain. The decision to use G-CSF should consider initial neutrophil count, presence of severe infection or sepsis, age, and comorbidities. Despite the accumulated experience, randomized controlled trials are still lacking, and treatment algorithms remain empirical. Full article

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14 pages, 4320 KB

Open AccessEditor’s ChoiceArticle

Therapeutic Potential of Exportin 1 and Aurora Kinase A Inhibition in Multiple Myeloma Cells

by Seiichi Okabe, Yuko Tanaka, Shunsuke Otsuki, Mitsuru Moriyama, Seiichiro Yoshizawa, Akihiko Gotoh and Daigo Akahane

Hematol. Rep. 2026, 18(1), 10; https://doi.org/10.3390/hematolrep18010010 - 9 Jan 2026

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Abstract

Background/Objectives: Aurora kinases (AURKs) are key regulators of mitosis, and their dysregulation contributes to plasma cell disorders, including multiple myeloma (MM) and plasma cell leukemia (PCL). Methods: The expression and prognostic relevance of AURK family members were examined, and the therapeutic potential of [...] Read more.

Background/Objectives: Aurora kinases (AURKs) are key regulators of mitosis, and their dysregulation contributes to plasma cell disorders, including multiple myeloma (MM) and plasma cell leukemia (PCL). Methods: The expression and prognostic relevance of AURK family members were examined, and the therapeutic potential of AURKA inhibition was evaluated. Results: Gene expression analysis demonstrated significant upregulation of AURKA in PCL. Treatment of MM cells with the selective AURKA inhibitor LY3295668 induced dose-dependent cytotoxicity, caspase-3/7 activation, and cellular senescence. Similarly, selinexor, a selective exportin-1 inhibitor, elicited dose-dependent cytotoxicity and apoptosis. Combined treatment with LY3295668 and selinexor significantly improved apoptosis compared with either agent alone, and AURKA knockdown further sensitized MM cells to selinexor, thereby increasing apoptosis. In bortezomib-resistant MM cells and primary PCL samples, the combination therapy induced cytotoxicity and caspase-3/7 activation. Conclusions: These findings underscore AURKA expression as a prognostic marker in plasma cell disorders and support the therapeutic potential of combining AURKA inhibition with selinexor for bortezomib-resistant MM and PCL. To explore biomarker-driven strategies for optimizing therapeutic outcomes, future studies are warranted. Full article

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12 pages, 895 KB

Open AccessEditor’s ChoiceArticle

Fetal Safety of Intravenous Ferric Carboxymaltose in Pregnancy: A Cardiotocography Study from a Tertiary Care Hospital in Italy

by Francesca Polese, Chiara Pesce, Giulia De Fusco, Gianni Tidore, Enza Coluccia, Raffaele Battista and Gianluca Gessoni

Hematol. Rep. 2026, 18(1), 7; https://doi.org/10.3390/hematolrep18010007 - 5 Jan 2026

Viewed by 2283

Abstract

Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer [...] Read more.

Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer a viable therapeutic option in the third trimester of pregnancy. Ferric carboxymaltose (FCM; Ferinject^®) is an IV iron preparation that allows rapid administration of high single doses of iron with a favorable safety profile. This study evaluated the potential impact of FCM therapy on fetal well-being by recording cardiotocography (CTG) before, during, and after iron infusions. Materials and Methods: We examined 105 women with IDA in the third trimester of pregnancy. During the initial evaluation, each patient was assessed for complete blood count, iron metabolism, B12, folates, hemoglobinopathies, CRP, kidney and liver function, and glucose levels. Each subject received intravenous ferric carboxymaltose (FCM), 500 mg. The study focused on the maternal and fetal safety of FCM infusion. The primary endpoint for maternal safety was the observation of adverse effects of iron infusion. For fetal safety, the primary endpoint was the assessment of CTG. Results: We considered 105 women, comprising 101 singleton and 4 twin pregnancies. The median hemoglobin (Hb) at initial observation was 95 g/L and 117 g/L post-therapy. Regarding maternal safety, side effects were observed during or after FCM infusion in four subjects; three cases involved local symptoms, while one case included nausea and skin rash. Concerning fetal safety, 100% of the cardiotocography records were deemed “normal” using the Dawes–Redman criteria. Conclusions: In conclusion, FCM proved effective in treating anemia in this clinically complex population of pregnant women in the third trimester and appeared safe in this cohort, though larger prospective studies are warranted. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

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21 pages, 1141 KB

Open AccessEditor’s ChoiceReview

Iron Therapy in Pediatric Iron Deficiency and Iron-Deficiency Anemia: Efficacy, Safety, and Formulation-Specific Trade-Offs—A Narrative Review

by Guido Leone, Marta Arrabito, Giovanna Russo and Milena La Spina

Hematol. Rep. 2026, 18(1), 6; https://doi.org/10.3390/hematolrep18010006 - 3 Jan 2026

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Abstract

Background/Objectives: Iron deficiency (ID) is the most common nutritional disorder in childhood worldwide. It has profound consequences for growth, neurodevelopment, behaviour, and overall health. Despite the long-standing efficacy of oral ferrous salts, their poor gastrointestinal tolerability and adherence challenges have spurred the [...] Read more.

Background/Objectives: Iron deficiency (ID) is the most common nutritional disorder in childhood worldwide. It has profound consequences for growth, neurodevelopment, behaviour, and overall health. Despite the long-standing efficacy of oral ferrous salts, their poor gastrointestinal tolerability and adherence challenges have spurred the development of alternative formulations and innovative dosing strategies. Methods: We conducted a narrative review of national and international guidelines, pediatric randomized controlled trials, observational and cohort studies, cost-effectiveness analyses, diagnostic method papers, and reviews, with emphasis on diagnostic innovations, therapeutic outcomes, tolerability, and formulation-specific efficacy. Results: Ferrous salts remain the gold standard for efficacy, low cost, and guideline endorsement, but up to 40% of children experience GI intolerance. Therefore, a lower dosage of ferrous salts has been proposed for IDA as still being an efficacious and better-tolerated schedule. Also, alternate-day dosing improves absorption and tolerability and is supported by a recent pediatric RCT. Newer formulations—ferric polymaltose, ferrous bisglycinate, co-processed bisglycinate with alginate (Feralgine™), and vesicular encapsulated forms such as sucrosomial and liposomal ferric pyrophosphate—showed improved tolerability and palatability, supporting adherence with hematologic outcomes comparable to ferrous salts, particularly in children with intolerance, malabsorption, or inflammatory comorbidities. Intravenous iron is effective and safe with modern preparations and is reserved for severe anemia, malabsorption, or oral therapy failure. Conclusions: Oral ferrous salts should remain the first-line therapy in pediatric ID/IDA. Future pediatric trials should prioritize head-to-head comparisons of formulations, hepcidin-guided dosing, and patient-centred outcomes, including neurocognitive trajectories and quality of life. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

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13 pages, 528 KB

Open AccessEditor’s ChoiceReview

Advances in Gene Therapy for Inherited Haemoglobinopathies

by Anna B. Gaspar and H. Bobby Gaspar

Hematol. Rep. 2026, 18(1), 4; https://doi.org/10.3390/hematolrep18010004 - 27 Dec 2025

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Abstract

Haemoglobinopathies, including β-thalassaemia and sickle cell disease (SCD), are among the most common monogenic disorders worldwide and remain major causes of morbidity and early mortality. Historically, management of these life-altering diseases has relied on supportive treatment and symptom management and, although these treatments [...] Read more.

Haemoglobinopathies, including β-thalassaemia and sickle cell disease (SCD), are among the most common monogenic disorders worldwide and remain major causes of morbidity and early mortality. Historically, management of these life-altering diseases has relied on supportive treatment and symptom management and, although these treatments reduce symptoms and ease disease burden, they do not correct the underlying genetic defect. Allogenic haematopoietic stem cell transplantation (HSCT) has been the only established curative option; however, it comes with substantial risks that significantly restrict its applicability. Over the past two decades, haematopoietic stem cell (HSC) gene therapy for haemoglobinopathies has rapidly progressed from experimental proof-of-concept to approved therapies. Lentiviral gene addition approaches have demonstrated durable expression of functional β-like globin transgenes, achieving transfusion independence in β-thalassaemia patients and significant reductions in vaso-occlusive events in SCD patients. Alternative therapeutic approaches to promote HbF expression have proved to be highly successful. Gene silencing strategies targeting BCL11A have been successful clinically and, more recently, gene editing technologies such as CRISPR/Cas9 have enabled precise disruption of regulatory elements controlling γ-globin repression, leading to the approval of the first CRISPR-based therapy for SCD and β-thalassaemia. Emerging base editing technologies promise even more precise genetic modification and are advancing through clinical evaluation. Despite these advances, access to gene therapy remains restricted due to the need for highly specialised manufacturing, toxic myeloablative conditioning regimens, and high treatment costs. Ongoing improvements and adaptations in these areas are essential to ensure that gene therapies fulfil their potential as accessible, curative treatments for patients suffering from haemoglobinopathies worldwide. Full article

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28 pages, 807 KB

Open AccessEditor’s ChoiceReview

Clinical and Biological Insights into Myelodysplastic Neoplasms Associated with Deletions of Chromosome 5q Region

by Ugo Testa, Germana Castelli and Elvira Pelosi

Hematol. Rep. 2025, 17(6), 67; https://doi.org/10.3390/hematolrep17060067 - 29 Nov 2025

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Abstract

The only cytogenetic alteration defining a subtype of a myelodysplastic syndrome is represented by the deletion of the long arm of chromosome 5 (del(5q)), now classified as MDS with isolated del(5q). This subtype is associated with a peculiar phenotype mainly dependent on the [...] Read more.

The only cytogenetic alteration defining a subtype of a myelodysplastic syndrome is represented by the deletion of the long arm of chromosome 5 (del(5q)), now classified as MDS with isolated del(5q). This subtype is associated with a peculiar phenotype mainly dependent on the haploinsufficiency of several genes located on the deleted arm of chromosome 5. These patients show a good prognosis and respond to treatment with lenalidomide, but some cases progress to acute myeloid leukemia. Molecular studies have, in part, elucidated the heterogeneity of MDS with isolated del(5q), mainly related to the association with different co-mutations that may affect leukemic transformation and survival. In other MDS patients, del(5q) is combined with other chromosomal abnormalities, giving rise to a condition of complex karyotype, associated with frequent TP53 mutations and with a poor prognosis. Two different molecular pathways seem to be responsible for the generation of MDS with isolated del(5q) or of MDS with del(5q) associated with a complex karyotype. Full article

(This article belongs to the Special Issue Innovations in Hematologic Oncology: SOHO Italy Perspectives)

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22 pages, 21230 KB

Open AccessEditor’s ChoiceArticle

PD-1 Expression Promotes Immune Evasion in B-ALL

by Ana Casado-García, Gonzalo García-Aguilera, Julio Pozo, Ninad Oak, Susana Barrena, Belén Ruiz-Corzo, Jaanam Lalchandani, Ana Chamorro-Vera, Ana Castillo-Robleda, Beatriz Soriano, Silvia Alemán-Arteaga, Elena G. Sánchez, Jorge Martínez-Cano, Andrea López-Álvarez de Neyra, Paula Somoza-Cotillas, Oscar Blanco, Susana Riesco, Pablo Prieto-Matos, Francisco Javier García Criado, María Begoña García Cenador, César Cobaleda, Carolina Vicente-Dueñas, Kim E Nichols, Alberto Orfao, Manuel Ramírez-Orellana and Isidro Sánchez-García Show full author list Hide full author list

Hematol. Rep. 2025, 17(6), 61; https://doi.org/10.3390/hematolrep17060061 - 12 Nov 2025

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Abstract

Background/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise “silent” preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression [...] Read more.

Background/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise “silent” preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered by Pax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host’s NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL. Conclusions: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL. Full article

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12 pages, 1263 KB

Open AccessEditor’s ChoiceArticle

AI Improves Agreement and Reduces Time for Quantifying Metabolic Tumour Burden in Hodgkin Lymphoma

by May Sadik, Sally F. Barrington, Johannes Ulén, Olof Enqvist, Elin Trägårdh, Babak Saboury, Anne Lerberg Nielsen, Annika Loft, Jose Luis Loaiza Gongora, Jesus Lopez Urdaneta, Rajender Kumar, Martijn van Essen and Lars Edenbrandt

Hematol. Rep. 2025, 17(6), 60; https://doi.org/10.3390/hematolrep17060060 - 7 Nov 2025

Cited by 1 | Viewed by 1173

Abstract

Background: The aim was to evaluate whether an artificial intelligence (AI)-based tool for the automated quantification of the total metabolic tumour volume (tMTV) in patients with Hodgkin lymphoma (HL) could support nuclear medicine specialists in lesion segmentation and thereby enhance inter-observer agreement. Methods: [...] Read more.

Background: The aim was to evaluate whether an artificial intelligence (AI)-based tool for the automated quantification of the total metabolic tumour volume (tMTV) in patients with Hodgkin lymphoma (HL) could support nuclear medicine specialists in lesion segmentation and thereby enhance inter-observer agreement. Methods: Forty-eight consecutive patients who underwent staging with [18F]FDG PET/CT were included. Eight invited specialists from different hospitals were asked to manually segment lesions for tMTV calculations in 12 cases without AI advice, and to use automated AI segmentation in a further 12 cases, with editing as required, i.e., segmenting/adjusting 24 cases each. Each case was segmented by two specialists manually and by two different specialists using the AI tool, allowing for the pairwise comparison of inter-observer variability. Results: The median difference between two specialists performing manual tMTV segmentations was 26 cm³ (IQR 10–86 cm³) corresponding to 23% (IQR 7–50%) of the median tMTV in the dataset, while the median difference between two specialists tMTV adjustments using AI segmentations was 12 cm³ (IQR 4–39 cm³) corresponding to 9% (IQR 2–21%) (p = 0.023). The median difference in tMTV between measurements with and without AI was 3.3 cm³, corresponding to 2.3% of the median tMTV. Conclusions: An automated AI-based tool can significantly increase agreement among specialists quantifying tMTV in HL patients staged with [18F]FDG PET/CT, without markedly changing the measurements. Full article

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15 pages, 516 KB

Open AccessEditor’s ChoiceReview

MECOM-Rearranged Acute Myeloid Leukemia: Pathobiology and Management Strategies

by Utsav Joshi and Rory M. Shallis

Hematol. Rep. 2025, 17(6), 59; https://doi.org/10.3390/hematolrep17060059 - 31 Oct 2025

Cited by 1 | Viewed by 3315

Abstract

Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy, characterized by marked biological heterogeneity and variable clinical outcomes. Among its rarer genetic subsets is AML with rearrangements of the MDS1 and EVI1 complex locus (MECOM), occurring in fewer than 2% [...] Read more.

Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy, characterized by marked biological heterogeneity and variable clinical outcomes. Among its rarer genetic subsets is AML with rearrangements of the MDS1 and EVI1 complex locus (MECOM), occurring in fewer than 2% of newly diagnosed cases. This review examines the biology and clinical significance of MECOM-rearranged AML, with a focus on its diverse mechanisms of leukemogenesis, including chromosomal inversion and translocation involving 3q26. We discuss how aberrant EVI1/MECOM activity alters gene expression networks and drives malignant transformation. Current therapeutic approaches—including intensive chemotherapy, hypomethylating agents in combination with venetoclax, and allogeneic stem cell transplantation—are evaluated with particular emphasis on inv(3) and other t(3q26) subtypes. Despite these treatment strategies, outcomes remain poor, underscoring the urgent need for novel, more effective therapies for this high-risk form of AML. Full article

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12 pages, 263 KB

Open AccessEditor’s ChoiceReview

Navigating the New Era in Myelodysplastic Neoplasms: A Review of Prognostic Implications of the IPSS-M Score and 2022 WHO Classification

by Mihai-Emilian Lapadat, Oana Stanca, Nicoleta Mariana Berbec, Cristina Negotei and Andrei Colita

Hematol. Rep. 2025, 17(6), 58; https://doi.org/10.3390/hematolrep17060058 - 30 Oct 2025

Cited by 3 | Viewed by 2111

Abstract

Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. [...] Read more.

Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. In 2022, significant advancements reshaped both the classification and prognostic stratification of MDSs. The revised WHO Classification introduced crucial genetically defined subtypes, particularly those involving biallelic TP53 inactivation and SF3B1 mutations, shifting the emphasis from traditional morphology-based criteria to molecular ones. Simultaneously, morphological subtypes such as hypoplastic and hyperfibrotic MDSs were established as distinct entities with unique prognostic implications. At the same time, the introduction of the International Molecular Prognostic Scoring System (IPSS-M) provided a more precise prognostic stratification by integrating comprehensive molecular data alongside traditional clinical and cytogenetic parameters. Several validation studies have confirmed IPSS-M’s superior discriminative power compared to previous models, notably IPSS-R, improving predictions regarding overall survival and leukemia transformation. Nevertheless, practical considerations regarding the widespread application of IPSS-M have emerged, including concerns over economic feasibility and accessibility of advanced molecular testing methods, such as extensive Next-Generation Sequencing panels. This review synthesizes the recent literature and critical studies validating these classification and prognostic updates, discussing their clinical impact, practical considerations, and implications for targeted therapeutic strategies. By focusing on molecular pathogenesis, the latest classification systems and prognostic models promise significant advances in patient-specific management, setting the stage for future innovations in treatment and improved patient outcomes. Full article

10 pages, 819 KB

Open AccessEditor’s ChoiceArticle

Role of Daratumumab, Lenalidomide, and Dexamethasone in Transplantation-Eligible Patients with Multiple Myeloma After the Failure of Bortezomib-Based Induction Therapy

by Shun Ito, Takashi Hamada, Masaru Nakagawa, Takashi Ichinohe, Hironao Nukariya, Toshihide Endo, Kazuya Kurihara, Yuichi Takeuchi, Shimon Otake, Hiromichi Takahashi, Hideki Nakamura and Katsuhiro Miura

Hematol. Rep. 2025, 17(6), 57; https://doi.org/10.3390/hematolrep17060057 - 29 Oct 2025

Viewed by 1969

Abstract

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established. Methods: We retrospectively evaluated ASCT-eligible patients with MM who received second-line [...] Read more.

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established. Methods: We retrospectively evaluated ASCT-eligible patients with MM who received second-line therapy with DRd after initial induction therapy with VCd between 2017 and 2023 (salvage group). For comparison, patients who successfully underwent per-protocol treatment with VCd induction, followed by ASCT during the same period, were selected (control group). Results: Eight patients with a median age of 61 years (range, 36–68 years) were included in the salvage group. After a median of 5 DRd cycles, the best response was partial response (PR) in two patients (25%) and a very good partial response (VGPR) in six (75%). All patients underwent ASCT, resulting in PR in one (13%), VGPR in four (50%), and stringent complete response in three (38%). Measurable residual disease (MRD) assessed using multicolor flow cytometry was negative in four patients (50%). The controls included thirteen patients with a median age of 60 years (range, 44–64 years). While most patients in both groups received various post-ASCT therapies, the post-ASCT 2-year time to the next treatment rate was slightly better in the salvage group than in the control group (88% vs. 49%, p = 0.089). However, hypogammaglobulinemia was more common in the salvage group (75% vs. 15%, p = 0.018). Conclusions: This small case series suggests that DRd is promising for ASCT-eligible patients with MM after VCd failure. Full article

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20 pages, 1094 KB

Open AccessEditor’s ChoiceReview

The Gut Microbiome Role in Multiple Myeloma: Emerging Insights and Therapeutic Opportunities

by Mina Y. George, Nada K. Gamal, Daniel E. Mansour, Ademola C. Famurewa, Debalina Bose, Peter A. Messiha and Claudio Cerchione

Hematol. Rep. 2025, 17(6), 56; https://doi.org/10.3390/hematolrep17060056 - 27 Oct 2025

Cited by 5 | Viewed by 3179

Abstract

Multiple myeloma is a hematological cancer depicted by the proliferation of plasma cells within the bone marrow, causing immune dysfunction and other abnormalities. The gut microbiome, the microbial community in the gastrointestinal tract, was found to modulate systemic immunity, inflammation, and metabolism. Although [...] Read more.

Multiple myeloma is a hematological cancer depicted by the proliferation of plasma cells within the bone marrow, causing immune dysfunction and other abnormalities. The gut microbiome, the microbial community in the gastrointestinal tract, was found to modulate systemic immunity, inflammation, and metabolism. Although the interplay between gut microbiome and multiple myeloma has been found in recent research, there is a gap in knowledge linking the effect of the microbiome on the pathogenesis and treatment of multiple myeloma. The imbalance in the gut microbiome, dysbiosis, may influence multiple myeloma pathogenesis through immune modulation and inflammation. Certain microbial species have been associated with multiple myeloma progression, complications, and therapeutic responses to treatment. Moreover, microbiome-derived metabolites, short-chain fatty acids, can influence the immune circuits associated with multiple myeloma progression. Understanding the bidirectional relationship between multiple myeloma and gut microbiota may provide insights into enhanced treatment and the development of new microbiome-based interventions. The current review provides a comprehensive highlight of current evidence linking the gut microbiome with multiple myeloma, demonstrating its significant roles in the development, progression, and treatment of multiple myeloma. Additionally, it focuses on the therapeutic potential of modulating the gut microbiome as a novel adjunct strategy in multiple myeloma management. Full article

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14 pages, 447 KB

Open AccessEditor’s ChoiceArticle

Outcomes for Primary Central Nervous System Lymphoma from a Single Institution

by Sruthi Dontu, Jacob Boccucci, Michael Chahin, Amany Keruakous, Anand Jillella, Jorge Cortes, Vamsi Kota, Locke Bryan and Ayushi Chauhan

Hematol. Rep. 2025, 17(6), 55; https://doi.org/10.3390/hematolrep17060055 - 24 Oct 2025

Viewed by 2802

Abstract

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center. Methods: A single retrospective chart review was [...] Read more.

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center. Methods: A single retrospective chart review was conducted on all PCNSL patients from 2013 to 2023 to assess for various factors influencing care. Results: Of a total of 38 PCNSL patients, 6 died and 2 were lost to follow-up prior to therapy initiation, leading to a total of 30 patients for analysis. The median age was 62.3 (21–82 years). One patient had HIV/AIDS. Two patients were on immunosuppression for either kidney transplant or multiple sclerosis (MS). The HIV and MS cases were Epstein-Barr Virus (EBV)-positive. Completion of ≥six cycles of induction was predictive of response. Conclusions: PCNSL remains an area of high unmet need. Recent studies have shown that HD-MTX-based therapy and autologous stem cell transplantation afterwards leads to improved outcomes regardless of age; however, non-relapse mortality is important to consider. Our data from a primarily elderly and sub-rural cohort reiterate the efficacy of combination chemoimmunotherapy and impact of induction cycle number on response, regardless of age. A multidisciplinary approach and targeted agent maintenance should be considered to improve outcomes in the elderly. Full article

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20 pages, 2489 KB

Open AccessEditor’s ChoiceArticle

Vitamin K Antagonists (VKAs) and Novel Oral Anticoagulants (NOACs) Safety Comparison Based on Data from EudraVigilance Database

by Pier Paolo Olimpieri, Fanny Erika Palumbo, Gaetano Giuffrida, Edoardo Milanetti, Cecilia Gozzo, Elisa Lucia Scebba, Giovanni Luca Romano, Giovanni Enrico Lombardo, Andrea Duminuco, Calogero Vetro, Davide Giuseppe Castiglione, Giuseppe Alberto Palumbo, Salvatore Scarso, Filippo Drago and Lucia Gozzo

Hematol. Rep. 2025, 17(5), 54; https://doi.org/10.3390/hematolrep17050054 - 18 Oct 2025

Cited by 1 | Viewed by 1959

Abstract

Background: Clinical trials comparing novel oral anticoagulants (NOACs) with warfarin reported a lower mortality rate and a reduced incidence of bleeding with NOACs. However, these studies do not allow for final conclusions about safety. Moreover, direct comparisons among NOACs are not available. [...] Read more.

Background: Clinical trials comparing novel oral anticoagulants (NOACs) with warfarin reported a lower mortality rate and a reduced incidence of bleeding with NOACs. However, these studies do not allow for final conclusions about safety. Moreover, direct comparisons among NOACs are not available. Objectives: The aim of this study was to analyze data from EudraVigilance in order to compare OAC safety profiles. Methods: We searched for all suspected adverse drug reactions (ADRs) from OACs collected in the EudraVigilance up to March 2019. We calculated the reporting odds ratios (RORs) in order to assess the risk of reporting specific ADRs among drugs. Moreover, OAC safety profiles were investigated through correspondence analysis and visualized in contribution biplots. Results: A total of 244,149 individual case safety reports (ICSRs; 431,354 ADRs) related to OACs were retrieved from EudraVigilance. About 80% of ICSRs refer to NOACs, especially rivaroxaban. Gastrointestinal (Gastr) and central nervous system (Nerv) disorders were the most represented categories. More than 90% of ADRs were serious and almost 9% fatal, with the highest ROR reported for dabigatran. Both fatal and non-fatal ADRs reported for Vitamin K Antagonists (VKAs) differed from those reported for NOACs. Among the latter, dabigatran and rivaroxaban showed similar profiles, while apixaban differed from all other OACs, even in the case of fatal ADRs. Conclusions: As expected, data collected from EudraVigilance showed differences among drugs, probably related to their specific characteristics and/or the peculiar utilization in clinical practice. Further investigations are needed to better compare the safety profile of OACs. Full article

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9 pages, 642 KB

Open AccessEditor’s ChoiceArticle

Real-World Assessment of Pharmacokinetics, Clinical Outcomes, and Costs After Switching from Standard Half-Life to Extended Half-Life FVIII in Well-Controlled Hemophilia A Patients

by Maria Choví-Trull, Juan Eduardo Megías-Vericat, Santiago Bonanad-Boix, Saturnino Haya-Guaita, Ana Rosa Cid-Haro, Marta Aguilar-Rodriguez, Tomás Palanques-Pastor, Javier Garcia-Pellicer and Jose Luis Poveda-Andrés

Hematol. Rep. 2025, 17(5), 53; https://doi.org/10.3390/hematolrep17050053 - 17 Oct 2025

Viewed by 1323

Abstract

Objective: This study aimed to analyze pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life (SHL) factor VIII (FVIII) to extended half-life (EHL) PEGylated turoctocog alfa pegol in patients with severe/moderate hemophilia A (HA) on prophylaxis, [...] Read more.

Objective: This study aimed to analyze pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life (SHL) factor VIII (FVIII) to extended half-life (EHL) PEGylated turoctocog alfa pegol in patients with severe/moderate hemophilia A (HA) on prophylaxis, one year prior to and following the switch in a real-world setting. Methods: A single-center, comparative, observational, sequential, retrospective, multidisciplinary study was designed. The population pharmacokinetic parameters were estimated using the WAPPS-Hemo^® platform. The annualized bleeding rate (including total and joint bleeds), joint health (Hemophilia Joint Health Score), FVIII consumption, administration frequency, and treatment costs were analyzed. Results: Eight patients with severe (n = 7) or moderate (n = 1) HA on prophylaxis were included after switching to turoctocog alfa pegol. With this regimen, the median FVIII half-life was 16.8 (15.2–19.1) hours, the area under the curve (AUC) was 18,182 (12,879–21,214) IU·h/dL, and the incremental recovery was 2.2 IU/dL per (1.6–2.4) IU/kg. The patients required a median of 2.0 infusions per week (2.0–2.0), corresponding to a weekly consumption of 57.8 (54.2–61.1) IU/kg. Clinically, the prophylactic regimen was associated with fewer infusions per week, stable joint health, and a reduction in overall treatment costs. Conclusions: Prophylaxis with turoctocog alfa pegol provided the expected pharmacokinetic profile of an EHL-FVIII concentrate, enabled a lower infusion frequency, and was linked to a decreased treatment burden and cost while maintaining joint health. Full article

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11 pages, 1412 KB

Open AccessEditor’s ChoiceArticle

Association of Cognitive Impairment with Reduced Health-Related Quality of Life and Depression Among Survivors of Thrombotic Thrombocytopenic Purpura

by Sruthi Selvakumar, Jia Yu, Jacob Meade and Shruti Chaturvedi

Hematol. Rep. 2025, 17(5), 51; https://doi.org/10.3390/hematolrep17050051 - 27 Sep 2025

Cited by 2 | Viewed by 978

Abstract

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors. [...] Read more.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors. Methods: iTTP survivors completed the Beck Depression Inventory (BDI-II), the SF-36 for evaluation of HRQoL, and the NIH Toolbox Cognition Battery. SF-36 scores and fluid cognition and crystallized cognition composite scores from the cognition battery were compared to the reference population. We examined associations of cognitive impairment with depression and HRQoL. Results: We enrolled 47 patients with iTTP; 76.6% were female, the median age was 51 (IQR 39, 60), and the median number of episodes was 2 (1, 3.5). Compared to the reference, iTTP survivors had significantly lower mean scores in seven SF-36 domains (physical function, physical limitation, general, mental health, vitality, social functioning, and emotional limitation) as well as the mental component score (MCS) (p < 0.0001) and physical component scores (PCS) (p < 0.0001). A lower physical HRQoL score was observed in those with mild (49.3 vs. 37.7, p = 0.005) and major (49.3 vs. 38.4, p = 0.007) CI compared to no CI. The fluid cognition composite score correlated strongly with the SF-36 Physical Component Summary (r = 0.548, p = 0.0002) but not the Mental Component Summary (r = 0.113, p = 0.489). Conclusions: Cognitive impairment in iTTP survivors is associated with reduced physical HRQoL. Identifying and addressing cognitive deficits in iTTP may improve HRQoL. Given that 40% of participants had depressive symptoms, which were associated with reduced mental HRQoL, iTTP survivors may also benefit from routine mental health screening t. Full article

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11 pages, 680 KB

Open AccessEditor’s ChoiceReview

Acquired Hypolipoproteinemia and Hemophagocytic Lymphohistiocytosis: A Case Series and Review

by Leo Reap, Ritwick S. Mynam, Radhika Takiar and Vincent T. Ma

Hematol. Rep. 2025, 17(5), 50; https://doi.org/10.3390/hematolrep17050050 - 22 Sep 2025

Viewed by 1616

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored. Methods: We [...] Read more.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored. Methods: We retrospectively reviewed 18 adult HLH cases diagnosed between 2012 and 2020 at two institutions where complete lipid profiles were obtained at or near diagnosis. HLH was defined according to HLH-2004 criteria. Results: Among 18 patients, 17 (94%) had secondary HLH, most commonly idiopathic (n = 5, 28%) or Epstein–Barr virus-associated (n = 3, 17%). Hypolipidemia was nearly universal: all (18/18) had HDL-C < 30 mg/dL, 15/18 (83%) had HDL-C < 20 mg/dL, and 12/18 (67%) had HDL-C < 10 mg/dL. LDL-C was <100 mg/dL in 12/18 (67%), with 6/18 (33%) undetectable. Triglycerides were variably elevated (median 279 mg/dL, range 96–1658 mg/dL). Three representative cases with profound hypolipoproteinemia demonstrated lipid normalization after HLH-directed therapy. Conclusions: Severe reductions in HDL-C and LDL-C appear to accompany HLH and may contribute to its pathophysiology by impairing antioxidant defenses, destabilizing membranes, and potentiating macrophage activation. This case series highlights a consistent association between hypolipoproteinemia and HLH, suggesting potential diagnostic value. However, the observational design and small cohort limit generalizability. Larger prospective studies are needed to clarify mechanisms and evaluate whether full lipid profiling should be incorporated into diagnostic algorithms. Full article

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12 pages, 225 KB

Open AccessEditor’s ChoiceReview

Haematologists as Genetic Counsellors for Haemoglobinopathies: Are They Prepared?

by Michael Angastiniotis and Androulla Eleftheriou

Hematol. Rep. 2025, 17(5), 48; https://doi.org/10.3390/hematolrep17050048 - 15 Sep 2025

Cited by 1 | Viewed by 1868

Abstract

Background/Objectives: In haematology, a wide range of blood disorders are hereditary. The thalassaemias are hereditary anaemias characterised by a high burden of disease at the public health level, challenging the resources of many health systems. This review focuses on thalassaemias for which [...] Read more.

Background/Objectives: In haematology, a wide range of blood disorders are hereditary. The thalassaemias are hereditary anaemias characterised by a high burden of disease at the public health level, challenging the resources of many health systems. This review focuses on thalassaemias for which many countries have developed screening and prevention programmes. To manage this heavy burden, two approaches were introduced over the years. The first one focused on reducing the annual affected births consequent to appropriate non-directive genetic counselling, offering to the parents the chance to make an informed choice concerning their reproductive lives. The second approach was related to the development of curative treatments such as haematopoietic stem cell transplantation (HSCT) in the early years, with continued ongoing efforts for improvements, followed by successful advances in gene-based holistic cures in more recent years. Genetic counselling is a vital component in successful prevention, aiming at informing individuals who are found to be carriers and couples who are both carriers with a 25% risk at every pregnancy of having an affected child in the case of recessive, Mendelian inheritance. The issues are many, and that may have to be discussed, highlighting the level of skills which a genetic counsellor is expected to possess and utilise appropriately in every counselling session. The concern is that such trained and skilled professionals are few in number and not well integrated into the multidisciplinary groups addressing the control of these complex disorders. It is our experience that for blood disorders, counselling is rarely in the hands of qualified scientists. It is our firm belief that it is necessary to incorporate genetic counselling as an integral part of haematology services. Methods: To investigate current practices we have drawn on the experience of existing programmes, as well as published literature. Results: Currently, in almost all haemoglobinopathy prevention programmes, counselling is offered by the clinicians in charge of clinical care or, in some settings, by the nurse of the clinic or the screening laboratory scientist. Conclusions: The Thalassaemia International Federation suggests and is in the process of developing special training in counselling as part of haematology training, as well as professional development modules for those already in practice. Considering the complexity of the issues that must be discussed, a multidisciplinary approach to counselling should be considered where possible. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

8 pages, 496 KB

Open AccessEditor’s ChoiceCase Report

Tyrosine Kinase Inhibitor Treatment of a Patient with Chronic Myeloid Leukemia and Congenital Thrombophilia

by Carol Herrera-Hernández, Adrián Segura-Diaz, Ruth Stuckey, Juan Francisco López-Rodríguez and María Teresa Gómez-Casares

Hematol. Rep. 2025, 17(5), 47; https://doi.org/10.3390/hematolrep17050047 - 12 Sep 2025

Cited by 1 | Viewed by 1252

Abstract

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, [...] Read more.

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications. Conclusions: This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk. Full article

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14 pages, 1311 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Prolonged Hematogone Expansion Is Associated with Better Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

by Bianca Serio, Danilo De Novellis, Marisa Gorrese, Angela Bertolini, Paola Manzo, Francesca Picone, Anna Maria Della Corte, Rossella Marcucci, Denise Morini, Michela Rizzo, Roberto Guariglia, Serena Luponio, Pasqualina Scala, Francesco Verdesca, Anna Maria Sessa, Francesca Velino, Martina De Leucio, Maddalena Langella, Valentina Giudice and Carmine Selleri

Hematol. Rep. 2025, 17(5), 46; https://doi.org/10.3390/hematolrep17050046 - 10 Sep 2025

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Abstract

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its [...] Read more.

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its association with clinical and molecular features. Results: Using a cut-off value of 0.1%, hematogones were detected in 60% of patients at the first re-evaluation after HSCT (median, 2.4%; range, 0.2–9.0%) and in 63% of subjects at the most recent evaluation (MRR) (median, 1.4%; range, 0.1–5.1%). In particular, prolonged hematogone expansion was associated with longer overall survival (p = 0.0043) and relapse-free survival (p = 0.0002). No associations were described between hematogone frequency and stem cell sources or acute or chronic graft versus host disease incidence. Conclusions: In conclusion, our results confirmed that hematogones mirrored bone marrow fitness and reconstitution ability; thus, they could be used as a prognostic marker of HSCT outcomes. Full article

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11 pages, 564 KB

Open AccessEditor’s ChoiceArticle

Interplay Between Sickle Cell Disease and Thrombosis: A Single Center Experience of Pathophysiology and Potential Risk Factors

by Rafail Tzanninis, Efthymia Vlachaki, Eleftheria Lefkou, Stavroula Tsiara, Stamatia Theodoridou, Athanasios Vyzantiadis and Miltiadis Matsagkas

Hematol. Rep. 2025, 17(5), 45; https://doi.org/10.3390/hematolrep17050045 - 3 Sep 2025

Cited by 1 | Viewed by 2069

Abstract

Background: Sickle cell disease (SCD) is among the most prevalent inherited hemoglobinopathies and is strongly associated with numerous coagulation abnormalities, hence constituting a severe hypercoagulable state. Methods: We conducted a single-center retrospective observational study of patients with SCD who were monitored at [...] Read more.

Background: Sickle cell disease (SCD) is among the most prevalent inherited hemoglobinopathies and is strongly associated with numerous coagulation abnormalities, hence constituting a severe hypercoagulable state. Methods: We conducted a single-center retrospective observational study of patients with SCD who were monitored at Hippokration Hospital of Thessaloniki between 1999 and 2024. Demographic characteristics, hemoglobin (Hb) genotype, medical history, anticoagulant and antiplatelet therapy, dosage of anticoagulant treatment, recurrence of the first episode of venous thromboembolism (VTE) and relevant laboratory values were examined as possible risk factors. Results: Among 46 patients, 12 (26.1%) developed thrombosis with the majority (75%) carrying the HbS/β-thal genotype. The prevalence of VTE in this study was 17.4%. Variables significantly associated with an increased risk of thrombosis included age at the time of thrombosis, patient age, use of anticoagulant treatment, anticoagulant dosage, antiplatelet therapy and type of transfusion (p < 0.05). On multivariate analysis, anticoagulant treatment and its dosage retained statistical significance (p < 0.05). Conclusions: These findings reinforce the strong association between SCD and thrombotic events. Despite the availability of a broad therapeutic armamentarium and increasing knowledge of the underlying disease mechanisms, the prevention and management of thrombosis in these patients remains a challenge. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

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11 pages, 556 KB

Open AccessEditor’s ChoiceReview

Spontaneous Muscle Bleeding During Oral Anticoagulation Therapy: When Should We Suspect an Underlying Tumor?

by Antonella Mameli, Francesco Marongiu, Mauro Podda, Adolfo Pisanu and Doris Barcellona

Hematol. Rep. 2025, 17(5), 44; https://doi.org/10.3390/hematolrep17050044 - 31 Aug 2025

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Abstract

Spontaneous intramuscular hematomas (SMHs) are rare but potentially serious complications of oral anticoagulation therapy. Although often attributed solely to anticoagulant use, such lesions may mask underlying soft tissue sarcomas or paraneoplastic conditions. We report the case of an 80-year-old man on warfarin who [...] Read more.

Spontaneous intramuscular hematomas (SMHs) are rare but potentially serious complications of oral anticoagulation therapy. Although often attributed solely to anticoagulant use, such lesions may mask underlying soft tissue sarcomas or paraneoplastic conditions. We report the case of an 80-year-old man on warfarin who presented with a painful thigh mass initially interpreted as a hematoma but ultimately diagnosed as a malignant fibrous histiocytoma (MFH). In addition, we provide a narrative review of published cases, focusing on clinical presentation, diagnostic challenges, imaging strategies, and outcomes. Key pitfalls leading to delayed diagnosis include attribution bias, inadequate imaging, and premature management decisions. Epidemiological data show that while the incidence of SMHs is estimated at 0.5–1.5% among patients on vitamin K antagonists, clinically significant cases are increasingly reported with direct oral anticoagulants (DOACs). Suggested measures include clinical algorithms to prompt imaging and biopsy in persistent masses, validation of magnetic resonance imaging (MRI) criteria, and the establishment of prospective registries, aimed at facilitating earlier recognition of malignant lesions and improving patient outcomes. These strategies may improve early detection of malignancy and optimize care in anticoagulated patients presenting with soft tissue lesions. Full article

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11 pages, 974 KB

Open AccessEditor’s ChoiceArticle

Reversible Platelet Aggregation Induced by Low-Temperature Storage in Heparinized Whole Blood Samples

by Yuriko Hayashi, Manato Miyazaki, Ryusuke Kimura, Ririka Arai, Miu Takada, Ayuko Takahashi and Hirokazu Kimura

Hematol. Rep. 2025, 17(5), 42; https://doi.org/10.3390/hematolrep17050042 - 22 Aug 2025

Viewed by 2638

Abstract

Background/Objectives: Platelet counts can be affected by storage conditions, potentially leading to pseudothrombocytopenia. The present study aimed to investigate temperature-dependent changes in platelet counts and morphology in whole blood samples anticoagulated with heparin or EDTA. We also examined the molecular mechanism of [...] Read more.

Background/Objectives: Platelet counts can be affected by storage conditions, potentially leading to pseudothrombocytopenia. The present study aimed to investigate temperature-dependent changes in platelet counts and morphology in whole blood samples anticoagulated with heparin or EDTA. We also examined the molecular mechanism of cold-induced aggregation via integrin GPIIb/IIIa–fibrinogen interaction using established bioinformatics technologies (docking simulation). Methods: Peripheral blood was collected from healthy volunteers (n = 6) and treated with either heparin or EDTA. The samples were stored at 4 °C, room temperature, or incubated at 37 °C. Platelet counts were measured using an automated hematology analyzer. The morphology of various blood cells in smears was assessed using the May-Grünwald Giemsa staining method. Docking simulations using an available software (HADDOCK 2.4) were performed to evaluate integrin–fibrinogen binding at different temperatures. Results: In automated blood cell counting, platelet counts in heparinized blood were significantly decreased under low-temperature conditions (4 °C), but this decrease was restored to levels comparable to those at room temperature upon warming to 37 °C (p < 0.05). No significant changes were observed in EDTA-treated samples. Microscopical findings showed platelet aggregation only in heparinized samples at 4 °C, with normal morphology restored upon warming (37 °C). Docking simulations estimated stronger integrin GPIIb/IIIa–fibrinogen binding at 4 °C than at 37 °C (p = 0.0286), suggesting temperature-dependent enhancement of molecular interactions. Conclusions: These findings indicate that heparin can induce reversible platelet aggregation at low temperatures in whole blood samples, leading to pseudothrombocytopenia. This phenomenon may be mediated by increased integrin GPIIb/IIIa–fibrinogen binding. Full article

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11 pages, 219 KB

Open AccessEditor’s ChoiceArticle

TKI Use and Treatment-Free Remission in Chronic Myeloid Leukemia: Evidence from a Regional Cohort Study in the Canary Islands

by Santiago Sánchez-Sosa, Ruth Stuckey, Adrián Segura Díaz, José David González San Miguel, Ylenia Morales Ruiz, Sunil Lakhawani Lakhawani, Jose María Raya Sánchez, Melania Moreno Vega, María Tapia Torres, Pilar López-Coronado, María de las Nieves Saez Perdomo, Marta Fernández, Cornelia Stoica, Cristina Bilbao Sieyro and María Teresa Gómez Casares

Hematol. Rep. 2025, 17(4), 39; https://doi.org/10.3390/hematolrep17040039 - 4 Aug 2025

Viewed by 1556

Abstract

Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined [...] Read more.

Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined as sustained deep molecular response (DMR) after discontinuing TKIs, has emerged as a viable clinical goal. This study evaluates real-world data from the Canary Islands Registry of CML (RCLMC) to explore outcomes, predictors, and the feasibility of TFR. Methods: This retrospective observational study included 393 patients diagnosed with CML-CP between 2007 and 2023. Molecular response was monitored according to international guidelines. Survival probabilities were estimated using the Kaplan–Meier method. Logistic regression analysis was performed to identify predictors of molecular relapses after TKI discontinuation. Results: Of the 383 patients who received TKI treatment, 58.3% achieved molecular response grade 2 (MR2) (BCR-ABL1 ≤ 1%), 95.05% achieved MR2, and 50.5% reached MR4 within the first year. Of the 107 patients attempting TFR, 73.2% maintained remission at 36 months. Relapses occurred in 24 patients, all regaining molecular response upon reintroduction of TKIs. No cases of disease progression were observed. Conclusions: Our findings support the feasibility and safety of TFR in a real-world clinical setting for well-selected patients, with outcomes consistent with international studies. The study underscores the importance of molecular monitoring and patient-specific strategies to optimize outcomes. Full article

8 pages, 726 KB

Open AccessEditor’s ChoiceCase Report

Anemia Due to Unexpected Zinc-Induced Copper Deficiency

by Nicholas Chun, Shehla Aman, Dan Xu, Jun Wang, Craig Zuppan and Albert Kheradpour

Hematol. Rep. 2025, 17(4), 35; https://doi.org/10.3390/hematolrep17040035 - 17 Jul 2025

Cited by 3 | Viewed by 13081

Abstract

Anemia due to acquired copper deficiency is most commonly the result of malabsorption or dietary deficiency. However, it can occasionally be due to excess zinc intake, which impairs the absorption of copper. Copper deficiency may result in vacuolated erythroid and myeloid precursors in [...] Read more.

Anemia due to acquired copper deficiency is most commonly the result of malabsorption or dietary deficiency. However, it can occasionally be due to excess zinc intake, which impairs the absorption of copper. Copper deficiency may result in vacuolated erythroid and myeloid precursors in the bone marrow, and sometimes features resembling myelodysplasia that, although not specific, may be an important clue to the diagnosis. Background and Clinical Significance: We report bone marrow findings in a child with anemia due to zinc-induced copper deficiency. Case Presentation: An 18-year-old female with cerebral palsy admitted for respiratory failure was found to have anemia and leukopenia with absolute neutropenia. A bone marrow smear showed occasional ring sideroblasts. Additional testing revealed reduced serum copper and elevated serum zinc. Further inquiry uncovered a several-year history of high-dose zinc supplementation. Conclusions: It is important to consider copper deficiency as a potential etiology in patients with anemia and neutropenia, as it may otherwise be mistaken for vitamin B12 deficiency or myelodysplasia. The presence of small vacuoles in hematopoietic precursors is an important clue to the diagnosis and may help avoid ineffective interventions. Full article

(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)

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8 pages, 1283 KB

Open AccessEditor’s ChoiceCase Report

Multi-Organ Adverse Reaction to Two Hypomethylating Agents: A Challenge in High-Risk Myelodysplastic Syndrome Treatment

by Sofia Brites Alves and Francesca Pierdomenico

Hematol. Rep. 2025, 17(3), 29; https://doi.org/10.3390/hematolrep17030029 - 30 May 2025

Cited by 1 | Viewed by 1455

Abstract

Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. [...] Read more.

Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. In eligible patients, hypomethylating agents are used as a bridge for allogeneic stem cell transplantation, currently the only curative approach in these malignancies. The most common side effects of hypomethylating agents are myelosuppression, cutaneous injection site reactions (when azacitidine is given subcutaneously), and gastrointestinal symptoms. Uncommon, disabling, and long-lasting side effects represent a threat to effective treatment in this group of patients. Case Presentation: We describe the case of a 49-year-old male patient with IPSS-M intermediate-risk MDS, intended to receive first-line treatment with azacitidine followed by allogeneic stem cell transplantation. The first, late-onset azacitidine reaction was observed 48 h after the first exposure, with cutaneous and respiratory toxicity, followed by the late-onset recurrence of symptoms after azacitidine withdrawal and decitabine introduction. Conclusions: This case highlights atypical, disabling, and long-lasting drug reactions to two hypomethylating agents, with the persistence of hypersensitivity manifestations months after medication withdrawal. Full article

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8 pages, 748 KB

Open AccessEditor’s ChoiceCase Report

Management of Refractory Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adolescent Patients: A Case Series of Novel Therapeutics and Treatment Challenges

by Meha Krishnareddigari, Kenny Vo and Arun Panigrahi

Hematol. Rep. 2025, 17(3), 28; https://doi.org/10.3390/hematolrep17030028 - 20 May 2025

Cited by 2 | Viewed by 3801

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation with primary (genetic) and secondary (acquired) forms, including malignancy-associated HLH (m-HLH). The condition often presents significant diagnostic and therapeutic challenges due to overlapping symptoms with underlying malignancies and the absence of [...] Read more.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation with primary (genetic) and secondary (acquired) forms, including malignancy-associated HLH (m-HLH). The condition often presents significant diagnostic and therapeutic challenges due to overlapping symptoms with underlying malignancies and the absence of standardized guidelines for refractory cases. The established standard of care is dexamethasone and etoposide, but no guidelines exist for refractory HLH or cases triggered by malignancy. Case presentations: This case series describes three adolescent patients with m-HLH, focusing on complexities in diagnosis, treatment regimens, and toxicity management. While dexamethasone and etoposide remain a standard of care, their efficacy in refractory cases is limited. We highlight the novel use of targeted therapies, including emapalumab, an interferon-gamma inhibitor, and ruxolitinib, a JAK1/2 inhibitor, which showed potential in modulating immune hyperactivation. Conclusions: Our findings emphasize the need for individualized treatment approaches in adolescent m-HLH and importance of further research to establish evidence-based therapeutic guidelines for refractory cases. Full article

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10 pages, 356 KB

Open AccessEditor’s ChoiceArticle

Racial Inequities Influencing Admission, Disposition and Hospital Outcomes for Sickle Cell Anemia Patients: Insights from the National Inpatient Sample Database

by Jayalekshmi Jayakumar, Nikhil Vojjala, Manasa Ginjupalli, Fiqe Khan, Meher Ayyazuddin, Davin Turku, Kalaivani Babu, Srinishant Rajarajan, Charmi Bhanushali, Tijin Ann Mathew, Poornima Ramadas and Geeta Krishnamoorty

Hematol. Rep. 2025, 17(3), 27; https://doi.org/10.3390/hematolrep17030027 - 9 May 2025

Viewed by 2733

Abstract

Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis [...] Read more.

Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) from 2016 to 2020, identifying adult hospitalizations for SCD (HbSS genotype). Hospitalizations were categorized by race—White, African American, Hispanic, and other, and analyzed for demographic variables, admission types, disposition outcomes, and complications. Statistical analyses included chi-square tests and multivariate logistic regression, adjusting for confounders. Results: Of the 1,089,270 identified hospitalizations, 90.31% were African American. African American and Hispanic patients exhibited significantly higher non-elective admissions compared to Whites (77.81%). In-hospital mortality was highest among Hispanics (0.82%). Multivariate regression analysis revealed that African Americans and others had higher odds of prolonged hospital stays (Adjusted Odds Ratio (AOR): 1.30 and 1.20, respectively). African Americans and Hispanics also had increased risks of in-hospital complications of SCD. Conclusions: This study highlights substantial racial disparities in SCD hospitalizations, with African Americans and Hispanics facing poorer outcomes compared to Whites. Hispanics also demonstrated increased mortality. These findings underscore the need for targeted healthcare interventions to address racial inequities in SCD management and improve outcomes for all affected populations. Full article

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8 pages, 1036 KB

Open AccessEditor’s ChoiceBrief Report

Clinical Outcome and Molecular Profile in Patients with DDX41 Mutation Hot-Spots

by Nadia Toumeh, Yazan Jabban, Ahmad Nanaa, Rong He, David Viswanatha, Dragan Jevremovic, James M. Foran, Cecilia Y. Arana Yi, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, William J. Hogan, Mithun V. Shah, Abhishek A. Mangaonkar, Mrinal M. Patnaik, Hassan B. Alkhateeb and Aref Al-Kali

Hematol. Rep. 2025, 17(3), 26; https://doi.org/10.3390/hematolrep17030026 - 8 May 2025

Cited by 3 | Viewed by 2880

Abstract

Background/Objectives: DDX41, DEAD-box RNA helicase 41 gene located on chromosome 5q25.3, is one of the most mutated genes in patients with germline predisposition to myeloid neoplasms. Germline and somatic mutations often have different locations and patterns of mutation, with some hotspots [...] Read more.

Background/Objectives: DDX41, DEAD-box RNA helicase 41 gene located on chromosome 5q25.3, is one of the most mutated genes in patients with germline predisposition to myeloid neoplasms. Germline and somatic mutations often have different locations and patterns of mutation, with some hotspots displaying diversity based on ethnicity. We aimed to explore clinical outcomes in patients with various DDX41 hot-spot mutations. Methods: This was a retrospective study of patients at Mayo Clinic with DDX41 mutation identified through Next Generation Sequencing (NGS) between 2018 and 2024. We completed unadjusted comparisons using continuous or categorical variables, and survival rates were assessed using the Kaplan–Meier method and cox regression analysis. Results: Overall survival appears to be higher in those with p.M1| when compared to p.Asp140GlyFs*2 and p.Arg525His, with comparable survival between p.Arg525His and p.Asp140GlyFs*2. Among males with p.M1| who underwent bone marrow transplant, those who underwent bone marrow transplant appeared to have lower survival rates, although not statistically significant. Our study was limited by a small sample size, therefore limiting our ability to reach significance. Conclusions: Our findings suggest potential implications for clinical outcomes based on DDX41 mutation hot-spots. Full article

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12 pages, 2274 KB

Open AccessEditor’s ChoiceCase Report

Severe Aplastic Anemia Complicated with Fatal Invasive Fungal Infections in a Young Patient Harboring Perforin Gene Polymorphisms

by Maria I. Krithinaki, Ioannis Kokkinakis, Styliani Markatzinou, Christos Masaoutis, Elena Solomou, Ioanna Papakitsou, Nektaria Xirouchaki, Ioannis Liapis, Helen A. Papadaki and Charalampos G. Pontikoglou

Hematol. Rep. 2025, 17(3), 25; https://doi.org/10.3390/hematolrep17030025 - 6 May 2025

Cited by 1 | Viewed by 4237

Abstract

Background: Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and [...] Read more.

Background: Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and aspergillosis, constitute principal causes of morbidity and mortality in patients with SAA. Genetic predispositions, including perforin (PRF1) polymorphisms, may further complicate disease outcomes by impairing immune function. Case report: We describe a case of a 36-year-old female patient diagnosed with SAA, for whom IST was considered, due to the unavailability of a matched sibling donor for HSCT. The patient presented with a feverish condition and deep neck space abscesses were revealed by imaging, caused by invasive aspergillosis. To prioritize infection control, IST was postponed and antifungal therapy with abscess drainage was initiated. However, aspergillosis progressed, despite aggressive and prompt treatment, and ultimately resulted in sepsis, multiorgan failure, and death. In addition, mucormycosis was confirmed post-mortem. Two heterozygous PRF1 polymorphisms (c.272C>T and c.900C>T), were identified by genetic testing, which may have contributed to immune dysregulation and fungal dissemination. Conclusions: The complex interplay between managing SAA and addressing invasive fungal infections, which remain a leading cause of mortality in immunocompromised patients, is highlighted in this case. The latter emphasizes the importance of prompt diagnosis and targeted treatment to alleviate infection-related complications while maintaining care continuity for the hematologic disorder. The detection of PRF1 polymorphisms raises questions about their implication in immune regulation and disease trajectory, emphasizing the need for further research in this field. Full article

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11 pages, 247 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence (AI) and Drug-Induced and Idiosyncratic Cytopenia: The Role of AI in Prevention, Prediction, and Patient Participation

by Emmanuel Andrès, Amir El Hassani Hajjam, Frédéric Maloisel, Maria Belén Alonso-Ortiz, Manuel Méndez-Bailón, Thierry Lavigne, Xavier Jannot and Noel Lorenzo-Villalba

Hematol. Rep. 2025, 17(3), 24; https://doi.org/10.3390/hematolrep17030024 - 29 Apr 2025

Cited by 4 | Viewed by 2168

Abstract

Drug-induced and idiosyncratic cytopenias, including anemia, neutropenia, and thrombocytopenia, present significant challenges in fields like immunohematology and internal medicine. These conditions are often unpredictable, multifactorial, and can arise from a complex interplay of drug reactions, immune abnormalities, and other poorly understood mechanisms. In [...] Read more.

Drug-induced and idiosyncratic cytopenias, including anemia, neutropenia, and thrombocytopenia, present significant challenges in fields like immunohematology and internal medicine. These conditions are often unpredictable, multifactorial, and can arise from a complex interplay of drug reactions, immune abnormalities, and other poorly understood mechanisms. In many cases, the precise triggers and underlying factors remain unclear, making diagnosis and management difficult. However, advancements in artificial intelligence (AI) are offering new opportunities to address these challenges. With its ability to process vast amounts of clinical, genomic, and pharmacovigilance data, AI can identify patterns and risk factors that may be missed by traditional methods. Machine learning algorithms can refine predictive models, enabling earlier detection and more accurate risk assessments. Additionally, AI’s role in enhancing patient engagement—through tailored monitoring and personalized treatment strategies—ensures more effective follow-up and improved clinical outcomes for patients at risk of these potentially life-threatening conditions. Through these innovations, AI is paving the way for a more proactive and personalized approach to managing drug-induced cytopenias. Full article

28 pages, 370 KB

Open AccessEditor’s ChoiceReview

Primary Mediastinal B-Cell Lymphoma and [18F]FDG PET/CT: What We Learned and What Is New

by Anna Giulia Nappi, Francesco Dondi, Achille Lazzarato, Lorenzo Jonghi-Lavarini, Joana Gorica, Flavia La Torre, Giulia Santo and Alberto Miceli

Hematol. Rep. 2025, 17(3), 23; https://doi.org/10.3390/hematolrep17030023 - 28 Apr 2025

Cited by 3 | Viewed by 4855

Abstract

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of [...] Read more.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of debate and studies. In this scenario, [18F]FDG PET/CT plays a pivotal role both in characterizing the mediastinal mass, the main feature of PMLBCL, in staging, in restaging during therapy (interim PET), and at the end of treatment (EoT PET), to guide clinical management and give prognostic insights. The main issue with PMLBCL is distinguishing viable disease from residual fibrotic/inflammatory mass after therapy and, consequently, settling the next clinical strategy. Novel therapeutic approaches are ongoing and associated with the deepening of [18F]FDG PET/CT potentials as a principal tool in this context. In this review, we will explore PMLBCL from a Nuclear Medicine point of view to help clinicians in the management of these patients. Full article

10 pages, 966 KB

Open AccessEditor’s ChoiceArticle

Treatment of Non-Hodgkin Lymphoma Involving Head and Neck Sites with a 1.5 T MR-Linac: Preliminary Results from a Prospective Observational Study

by Andrea Emanuele Guerini, Stefania Nici, Stefano Riga, Ludovica Pegurri, Paolo Borghetti, Eneida Mataj, Jacopo Balduzzi, Mirsada Katica, Gianluca Cossali, Giorgio Facheris, Luca Triggiani, Albert Sakiri, Luigi Spiazzi, Stefano Maria Magrini and Michela Buglione

Hematol. Rep. 2025, 17(2), 16; https://doi.org/10.3390/hematolrep17020016 - 27 Mar 2025

Cited by 1 | Viewed by 2311

Abstract

Purpose: Lymphomas are generally radiosensitive; therefore, disease volume tends to shrink during radiotherapy courses. As MRI-linac provides excellent soft tissue definition and allows daily re-contouring of gross tumor volume and clinical target volume, its adoption could be beneficial for the treatment of [...] Read more.

Purpose: Lymphomas are generally radiosensitive; therefore, disease volume tends to shrink during radiotherapy courses. As MRI-linac provides excellent soft tissue definition and allows daily re-contouring of gross tumor volume and clinical target volume, its adoption could be beneficial for the treatment of lymphomas. Nonetheless, at this time there is a lack of literature regarding the use of MR-linac in this context. Methods: A prospective observational study was conducted on patients affected by non-Hodgkin lymphoma (NHL) involving head and neck (H&N) sites and treated with Elekta Unity^® MR-Linac. The clinical and dosimetric data of the first eight patients were collected and integrated with relevant data from medical records. Results: Seven patients had B-cell lymphoma (three DLBCL, two MALT, one follicular, and one mantle-cell) and one T-cell/NK lymphoma. The intent of RT was radical for four patients, salvage treatment for three, and CAR-T bridging for one. Two patients presented orbital localizations and six cervical lymphonodal sites. Median GTV was 5.74 cc, median CTV 127.01 cc, and median PTV 210.37 cc. The prescribed dose was 24–50 Gy in 2 Gy fractions for seven patients and 24 Gy in 3 Gy fractions for one patient. All the patients experienced acute toxicity, the maximum grade was G1 for five patients and G2 for three at the end of RT. One month after radiotherapy seven patients still experienced G1 toxicity, but no toxicity grade ≥ 2 was reported. First radiological assessment was performed for all the patients after a median of 101.5 days, reporting complete response in all the cases. After a median follow up of 330 days, no patient experienced local disease progression, while one patient developed distant progression. Conclusions: radiotherapy for NHL with H&N localization using a 1.5 T MR-linac was feasible, with no >G2 toxicity and optimal response rate and disease control. Full article

(This article belongs to the Special Issue Modern Radiotherapy for the Treatment of Lymphoma and Myeloma: Integration with Systemic Treatment and Advanced Imaging Techniques)

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8 pages, 204 KB

Open AccessEditor’s ChoiceCommunication

Avascular Necrosis of the Femoral Head in Patients with Antiphospholipid Syndrome: A Case Series

by Paschalis Evangelidis, Eleni Gavriilaki, Nikolaos Kotsiou, Zacharo Ntova, Panagiotis Kalmoukos, Theodosia Papadopoulou, Sofia Chissan and Sofia Vakalopoulou

Hematol. Rep. 2025, 17(2), 15; https://doi.org/10.3390/hematolrep17020015 - 21 Mar 2025

Cited by 7 | Viewed by 3217

Abstract

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) [...] Read more.

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) is considered a rare manifestation of APS. The aim of our case series is to study patients with APS and AN. Methods: A retrospective study was performed on 80 patients diagnosed with APS. Results: AN was observed in 3 patients out of 80 diagnosed with APS. AN of the femoral head was observed in all cases. Case (1): A 54-year-old woman presented due to multiple ischemic infarctions in the brain, as detected in magnetic resonance imaging of the brain, Raynaud’s phenomenon, and AN of the femoral head. In laboratory testing, a prolongation of activated partial thromboplastin time was recorded. A heterozygous mutation was also found in the gene MTHFR C677T, and the patients was positive for lupus anticoagulant (LA). The patient was given clopidogrel and acenocoumarol. Case (2): A 52-year-old man was diagnosed with APS, based on the clinical presentation (stroke) and positivity for LA and anti-β2GPI (anti-β2 glycoprotein I antibody). In his medical history, episodes of vertigo and an episode of AN of the femoral head 2 years ago were described. Case (3): A woman aged 43 years presented due to AN of the femoral head. Due to suspected APS, immunological testing was performed, and positivity for LA and IgM anticardiolipin antibodies was detected. She was treated with acenocoumarol. Conclusions: AN is a rare clinical manifestation of APS, which may precede the diagnosis of APS for many years. Full article

11 pages, 528 KB

Open AccessEditor’s ChoiceReview

Solid Tumors, Liquid Challenges: The Impact of Coagulation Disorders

by Nidha Shapoo, Noella Boma, Shobhana Chaudhari and Vladimir Gotlieb

Hematol. Rep. 2025, 17(1), 8; https://doi.org/10.3390/hematolrep17010008 - 5 Feb 2025

Cited by 2 | Viewed by 3133

Abstract

Coagulation disorders are increasingly recognized as significant complications in patients with solid tumors, affecting morbidity and mortality outcomes. Solid tumors can provoke a hypercoagulable state through the release of pro-coagulant factors, endothelial activation, and inflammation, leading to a heightened risk of coagulation disorders. [...] Read more.

Coagulation disorders are increasingly recognized as significant complications in patients with solid tumors, affecting morbidity and mortality outcomes. Solid tumors can provoke a hypercoagulable state through the release of pro-coagulant factors, endothelial activation, and inflammation, leading to a heightened risk of coagulation disorders. These coagulation disorders may manifest as venous thromboembolism, arterial thromboembolism, thrombotic microangiopathy, or disseminated intravascular coagulation. These disorders can complicate surgical interventions and impact treatments, including chemotherapy and immunotherapy efficacy, leading to poor outcomes. Understanding the implications of coagulation disorders in solid tumors is essential for optimizing patient management, including identifying high-risk patients, implementing prophylactic measures, elucidating biomarkers for clinical outcomes, and exploring novel therapeutic agents. This review aims to provide insights into the current knowledge surrounding coagulation disorders in solid tumors and their clinical implications. Full article

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17 pages, 1912 KB

Open AccessEditor’s ChoiceArticle

Risk Factors for Impaired Glucose Metabolism in Transfusion-Dependent Patients with β-Thalassemia: A Single-Center Retrospective Observational Study

by Theodora Maria Venou, Filippos Kyriakidis, Fani Barmpageorgopoulou, Stamatia Theodoridou, Athanasios Vyzantiadis, Philippos Klonizakis, Eleni Gavriilaki and Efthymia Vlachaki

Hematol. Rep. 2025, 17(1), 6; https://doi.org/10.3390/hematolrep17010006 - 30 Jan 2025

Cited by 3 | Viewed by 3157

Abstract

Background/Objectives: B-thalassemia is a genetic disorder that leads to reduced or absent β-globin chains, often resulting in endocrine abnormalities due to iron overload, chronic anemia, and hypoxia. This study investigates the prevalence and risk factors for glucose metabolism disturbances in transfusion-dependent β-thalassemia (TDT) [...] Read more.

Background/Objectives: B-thalassemia is a genetic disorder that leads to reduced or absent β-globin chains, often resulting in endocrine abnormalities due to iron overload, chronic anemia, and hypoxia. This study investigates the prevalence and risk factors for glucose metabolism disturbances in transfusion-dependent β-thalassemia (TDT) patients, focusing on pancreatic iron overload and its association with other iron biomarkers. Methods: We studied two groups of TDT patients (2018–2022) at Hippokration General Hospital: Group 1 (no glucose metabolism impairment, n = 46) and Group 2 (with impaired glucose tolerance or diabetes mellitus, n = 18). Patients were assessed for factors contributing to glucose disturbances, and laboratory data were analyzed. Type 2 diabetes was diagnosed per American Diabetes Association criteria, and impaired glucose tolerance was defined by OGTT results. A multivariate logistic regression identified potential independent risk factors. In a subset of patients on iron chelation therapy, we examined the relationship between pancreatic, liver, and heart iron overload (T2* MRI) and glucose/ferritin levels. Results: Age and elevated serum GGT levels were significantly associated with impaired glucose metabolism (p = 0.02). Beta-blocker use was correlated with glucose disturbances (p = 0.02), but multivariate analysis revealed no significant independent risk factors. A significant relationship was found between pancreatic and heart iron overload (r = 0.45, p = 0.04). Conclusions: Elevated GGT levels suggest that oxidative stress and liver dysfunction play a key role in glucose metabolism disturbances. Pancreatic MRI T2* may help predict heart iron overload. Further research is needed to identify reliable biomarkers for glucose regulation in TDT. Full article

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13 pages, 2912 KB

Open AccessEditor’s ChoiceArticle

The Role of Ferritin and Folate in Determining Stem Cell Collection for Autologous Stem Cell Transplant in Multiple Myeloma

by Charles J. Weeks, Mohammad Mian, Michael Stokes, Matthew Gold, Anvay Shah, Rohan Vuppala, Katherine J. Kim, Abigayle B. Simon, Jorge Cortes, Anand Jillela and Vamsi Kota

Hematol. Rep. 2025, 17(1), 5; https://doi.org/10.3390/hematolrep17010005 - 24 Jan 2025

Cited by 1 | Viewed by 3006

Abstract

Background: An autologous stem cell transplant (ASCT) is the standard of care for eligible patients with multiple myeloma (MM). However, the success of ASCT largely hinges on efficient mobilization; thus, a thorough analysis of factors that may affect mobilization is essential. Methods: The [...] Read more.

Background: An autologous stem cell transplant (ASCT) is the standard of care for eligible patients with multiple myeloma (MM). However, the success of ASCT largely hinges on efficient mobilization; thus, a thorough analysis of factors that may affect mobilization is essential. Methods: The study consists of a single-center, retrospective chart review of 292 adult patients undergoing their first or second autologous transplantation for MM from 2016 to 2023. Patient demographics, serum lab values at the pre-collection evaluation visit, total stem cell capture (TC) in CD34/kg × 10⁶ stem cell capture on the first day of apheresis (FC) in CD34/kg × 10⁶, and the total number of days of apheresis (DOA) were retrieved from the electronic medical record (EMR). Results: Individuals with high folate levels experienced less DOA (1.43 ± 0.61) compared to those with normal folate levels (1.68 ± 0.82, p = 0.013). The high-folate group had a greater FC (3.26 ± 1.07) compared to the normal-folate group (2.88 ± 1.13, p = 0.013). High ferritin levels were associated with more DOA (1.79 ± 0.89) compared to the normal-ferritin group (1.51 ± 0.67, p = 0.034). Moderate anemia was significantly associated with decreased FC (p = 0.023) and increased DOA (p = 0.030). Abnormal hemoglobin (Hgb), ferritin, and folate statuses did not exhibit significant differences in survival analysis. Conclusions: The findings reveal that folate, ferritin, and Hgb levels are significantly associated with apheresis outcomes, offering guidance for optimizing stem cell mobilization in patients with MM. Full article

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11 pages, 256 KB

Open AccessEditor’s ChoiceArticle

Incidence, Risk Factors, and Outcomes of Thrombocytopenia in Older Medical Inpatients: A Prospective Cohort Study

by Ioanna Papakitsou, Andria Papazachariou, Theodosios D Filippatos and Petros Ioannou

Hematol. Rep. 2024, 16(4), 804-814; https://doi.org/10.3390/hematolrep16040076 - 13 Dec 2024

Cited by 3 | Viewed by 3961

Abstract

Background: Thrombocytopenia, defined as a platelet count of less than 150 × 10⁹/L, is a frequent condition among hospitalized patients and presents unique challenges in diagnosis and management. Despite its commonality, data on incidence and related risk factors in medical inpatients [...] Read more.

Background: Thrombocytopenia, defined as a platelet count of less than 150 × 10⁹/L, is a frequent condition among hospitalized patients and presents unique challenges in diagnosis and management. Despite its commonality, data on incidence and related risk factors in medical inpatients remain limited, especially in older people. Methods: A 2-year prospective cohort study with a 3-year follow-up was conducted on inpatients aged ≥65 years admitted to a medical ward. Clinical data were collected, including demographics, comorbidities, laboratory results, and outcomes. Multivariate logistic regression analysis assessed risk factors associated with non-resolution of thrombocytopenia and mortality. Results: The study included 961 older inpatients with a mean age of 82 years. Thrombocytopenia occurred in 22.6% of the study population. The most common causes were infections (57.4%) and drug-induced thrombocytopenia (25.3%). The non-resolution of thrombocytopenia was noted in 59% of patients. In-hospital and 3-year mortality was significantly higher in this subgroup compared to the rest (24.5% vs. 12.7%, p = 0.015) and (72.4% vs. 59.8%, p = 0.04, respectively). In multivariate analysis, nadir platelet count and hematologic disease were independent factors associated with the non-resolution of thrombocytopenia. Furthermore, in individuals with thrombocytopenia, the administration of norepinephrine (p < 0.001) and a higher clinical frailty score (p < 0.001) were observed as independent mortality predictors. Conclusions: Thrombocytopenia in older medical inpatients is associated with poor prognosis, particularly in those with non-resolution thrombocytopenia. Early identification and targeted management may improve outcomes. Full article

14 pages, 1066 KB

Open AccessEditor’s ChoiceArticle

Incorporation of a Comorbidity Index in Treatment Decisions for Elderly AML Patients Can Lead to Better Disease Management—A Single-Center Experience

by Cristina Negotei, Iuliana Mitu, Silvana Angelescu, Florentina Gradinaru, Cristina Mambet, Oana Stanca, Mihai-Emilian Lapadat, Cristian Barta, Georgian Halcu, Carmen Saguna, Aurora Arghir, Mihaela Sorina Papuc, Andrei Turbatu, Nicoleta Mariana Berbec and Andrei Colita

Hematol. Rep. 2024, 16(4), 781-794; https://doi.org/10.3390/hematolrep16040074 - 3 Dec 2024

Cited by 2 | Viewed by 1753

Abstract

Introduction: Acute myeloid leukemia (AML) is a form of cancer originating from precursor cells within the bone marrow. Elderly patients with acute leukemia require a personalized approach, considering age, performance status, and comorbidities, to determine suitability for intensive treatment. Methods: We studied the [...] Read more.

Introduction: Acute myeloid leukemia (AML) is a form of cancer originating from precursor cells within the bone marrow. Elderly patients with acute leukemia require a personalized approach, considering age, performance status, and comorbidities, to determine suitability for intensive treatment. Methods: We studied the results of intense chemotherapy in 46 elderly, fit individuals with AML at a cancer center in Romania from January 2017 to December 2023. Results: The study involved a cohort of 46 patients, including 22 men and 24 women. The research indicated that 89.1% of the patients were diagnosed with de novo acute leukemia. Most patients had an ECOG score of 0–1, with one patient scoring ≥2. HCT-CI > 4 was found in 21 patients (45.7%), while CCI > 4 was present in 38 patients (82.6%). After the induction phase, 25 patients (54.3%) achieved complete remission (CR); the relapse rate was 56.8%. Upon completion of the study, nine individuals (19.6%) were still alive. The overall survival duration ranged from 0 to 33 months, with a median survival time of 8 months (CI 5.0–11.0). Conclusions: When considering treatment options for elderly patients, the Eastern Cooperative Oncology Group (ECOG) Performance Status, as well as comorbidity indices such as the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) and the Charlson Comorbidity Index (CCI), have shown promising results in the literature, indicating their relevance in the decision-making process. Full article

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17 pages, 753 KB

Open AccessEditor’s ChoiceSystematic Review

The Role of 11C-Methionine PET Imaging for the Evaluation of Lymphomas: A Systematic Review

by Francesco Dondi, Maria Gazzilli, Gian Luca Viganò, Antonio Rosario Pisani, Cristina Ferrari, Giuseppe Rubini and Francesco Bertagna

Hematol. Rep. 2024, 16(4), 752-768; https://doi.org/10.3390/hematolrep16040072 - 27 Nov 2024

Cited by 5 | Viewed by 2355

Abstract

Background: In the last years, different evidence has underlined a possible role for [11C]-methionine ([11C]MET) positron emission tomography (PET) imaging for the evaluation of lymphomas. The aim of this paper was, therefore, to review the available scientific literature focusing on this topic. [...] Read more.

Background: In the last years, different evidence has underlined a possible role for [11C]-methionine ([11C]MET) positron emission tomography (PET) imaging for the evaluation of lymphomas. The aim of this paper was, therefore, to review the available scientific literature focusing on this topic. Methods: A wide literature search of the PubMed/MEDLINE, Scopus and Cochrane Library databases was conducted in order to find relevant published articles investigating the role of [11C]MET in the assessment of lymphomas. Results: Eighteen studies were included in the systematic review and the main fields of application of this imaging modality were the evaluation of disease, therapy response assessment, prognostic evaluation and differential diagnosis with other pathological conditions. Conclusion: Even with heterogeneous evidence, a possible role for [11C]MET PET imaging in the assessment of lymphomas affecting both the whole body and the central nervous system was underlined. When compared to [18F]fluorodesoxyglucose ([18F]FDG) imaging, in general, similar results have been reported between the two modalities in these settings. Full article

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16 pages, 1143 KB

Open AccessEditor’s ChoiceReview

Treatment Strategies Used in Treating Myelofibrosis: State of the Art

by Massimo Martino, Martina Pitea, Annalisa Sgarlata, Ilaria Maria Delfino, Francesca Cogliandro, Anna Scopelliti, Violetta Marafioti, Simona Polimeni, Gaetana Porto, Giorgia Policastro, Giovanna Utano, Maria Pellicano, Giovanni Leanza and Caterina Alati

Hematol. Rep. 2024, 16(4), 698-713; https://doi.org/10.3390/hematolrep16040067 - 30 Oct 2024

Cited by 4 | Viewed by 8350

Abstract

Background: Current drug therapy for myelofibrosis does not alter the natural course of the disease or prolong survival, and allogeneic stem cell transplantation is the only curative treatment modality. For over a decade, the Janus kinase (JAK) inhibitor ruxolitinib has been the standard [...] Read more.

Background: Current drug therapy for myelofibrosis does not alter the natural course of the disease or prolong survival, and allogeneic stem cell transplantation is the only curative treatment modality. For over a decade, the Janus kinase (JAK) inhibitor ruxolitinib has been the standard of care. More recently, newer-generation JAK inhibitors have joined the ranks of accepted treatment options. Objectives: The primary goal of treatment is to reduce spleen size and minimize disease-related symptoms. Prognostic scoring systems are used to designate patients as being at lower or higher risk. For transplant-eligible patients, transplant is offered to those with a bridge of a JAK inhibitor; patients who are not eligible for transplant are usually offered long-term therapy with a JAK inhibitor. Limited disease-modifying activity, dose-limiting cytopenias, and other adverse effects have contributed to discontinuation of JAK inhibitor treatment. Conclusions: Novel JAK inhibitors and combination approaches are currently being explored to overcome these shortcomings. Further research will be essential to establish optimal therapeutic approaches in first-line and subsequent treatments. Full article

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13 pages, 965 KB

Open AccessEditor’s ChoiceArticle

Real-World Study of US Adults with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan

by Brian Mulherin, Apeksha Shenoy, Lily Arnett, Weiqi Jiao, Joseph Guarinoni, Sujata Sarda, Jinny Min and David Dingli

Hematol. Rep. 2024, 16(4), 669-681; https://doi.org/10.3390/hematolrep16040065 - 29 Oct 2024

Cited by 5 | Viewed by 3626

Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease characterized by complement-mediated hemolysis. OPERA is the first US longitudinal real-world study on C3 inhibitor therapy, known as pegcetacoplan. Methods: OPERA enrolled US patients with PNH, age ≥18, who were [...] Read more.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease characterized by complement-mediated hemolysis. OPERA is the first US longitudinal real-world study on C3 inhibitor therapy, known as pegcetacoplan. Methods: OPERA enrolled US patients with PNH, age ≥18, who were prescribed pegcetacoplan, and data were collected from routine care. Hemoglobin was reported by patients during regular follow-up (censored from transfusions). The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (0–52 score) and Patient-Reported Outcomes Measurement Information System scale for Cognitive Function Abilities (PROMIS-CF; 23.27–67.09 t-score) were completed electronically (low score = negative outcome). Patients self-reported incidence of healthcare resource utilization (HCRU). Results: By January 2024, 70 patients (mean age 44.6 years; 57.1% female) reported up to 9 months of pegcetacoplan treatment, with a median [IQR] follow-up of 6.6 [3.8] months. The latest reported hemoglobin levels improved by a mean (SD) of 2.6 (1.9) g/dL from baseline. At 3, 6 and 9 months, patients reported clinically meaningful improvements (≥5 points) in FACIT-F (53.3–69.0%) and (≥2 points) PROMIS-CF (46.7–55.2%). Patients reported a <10% incidence rate per person month of all HCRU events. Conclusions: This first longitudinal real-world US study indicates a positive trend in Hb, fatigue, and cognition with limited HCRU during pegcetacoplan treatment in adults with PNH. Full article

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12 pages, 1795 KB

Open AccessEditor’s ChoiceArticle

Utilizing Clinical Transformation Criteria for Prognostic Stratification in Follicular Lymphoma Prior to Initial Immunochemotherapy

by Yoshikazu Hori, Hiroki Hosoi, Takayuki Hiroi, Ke Wan, Shogo Murata, Masaya Morimoto, Toshiki Mushino, Akinori Nishikawa and Takashi Sonoki

Hematol. Rep. 2024, 16(4), 612-623; https://doi.org/10.3390/hematolrep16040060 - 4 Oct 2024

Cited by 2 | Viewed by 3714

Abstract

Background: Although the prognosis of follicular lymphoma (FL) has improved, some patients experience early disease progression, including progression of disease within 24 months (POD24). Histological transformation is a critical event in FL. However, the heterogeneity of FL tumors makes it challenging to diagnose [...] Read more.

Background: Although the prognosis of follicular lymphoma (FL) has improved, some patients experience early disease progression, including progression of disease within 24 months (POD24). Histological transformation is a critical event in FL. However, the heterogeneity of FL tumors makes it challenging to diagnose transformation accurately. We retrospectively applied the clinical transformation criteria used for FL transformation assessments at relapse or disease progression to conduct transformation assessments before the initial immunochemotherapy. Methods: Sixty-six FL patients who first received immunochemotherapy between January 2009 and February 2023 at our institution were selected. Twenty-three were clinical-transformation-positive (CLT+). Results: The progression-free survival (PFS) rate of the CLT+ patients was significantly lower than that of the clinical-transformation-negative (CLT−) patients. In the POD24 assessment subgroup, the CLT+ patients had a higher incidence of POD24 than the CLT− patients. There was no significant difference in PFS between the patients treated with CHOP-like regimens and those treated with bendamustine regimens. In the CHOP-like group, the CLT+ patients exhibited significantly lower PFS than the CLT− patients. In the bendamustine group, the clinical transformation did not affect PFS. Conclusion: Clinical transformation criteria may be useful for the prognostic stratification of FL prior to immunochemotherapy. Additionally, they may serve as predictors of POD24. Full article

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10 pages, 999 KB

Open AccessEditor’s ChoiceArticle

The Real-World Outcomes of Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab, Pomalidomide, and Dexamethasone

by Hitomi Nakayama, Yoshinobu Aisa, Chisako Ito, Aki Sakurai and Tomonori Nakazato

Hematol. Rep. 2024, 16(4), 593-602; https://doi.org/10.3390/hematolrep16040058 - 30 Sep 2024

Cited by 1 | Viewed by 2390

Abstract

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed [...] Read more.

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen’s Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5–23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1–15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1–13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients. Full article

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