Hematology Reports

11 pages, 247 KiB

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

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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

10 pages, 966 KiB

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

Viewed by 308

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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11 pages, 528 KiB

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

Viewed by 797

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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13 pages, 2912 KiB

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

Viewed by 967

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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14 pages, 1066 KiB

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 867

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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16 pages, 1143 KiB

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 1 | Viewed by 2367

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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12 pages, 1795 KiB

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

Viewed by 1809

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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9 pages, 3261 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Genomic Profiling in Non-Myeloid Hematologic Malignancies Identifies Variants That Can Alter Clinical Practice

by Chenyu Lin, Katherine I. Zhou, Michelle F. Green, Bennett A. Caughey, John H. Strickler, Michael B. Datto and Matthew S. McKinney

Hematol. Rep. 2024, 16(4), 603-611; https://doi.org/10.3390/hematolrep16040059 - 30 Sep 2024

Viewed by 1323

Abstract

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the [...] Read more.

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the frequency at which mutations identified by CGP altered management in non-myeloid hematologic malignancies. We retrospectively examined the CGP results of 105 samples from 101 patients with non-myeloid hematologic malignancies treated at an academic medical center who had CGP testing between 2014 and 2021. Results: CGP revealed one or more pathogenic or likely pathogenic variant in 92 (88%) of samples and 73 (72%) of tested patients had one or more mutations with diagnostic, prognostic, or therapeutic significance. The identification of a resistance variant resulted in the suspension of the active treatment or affected subsequent treatment choice in 9 (69%) out of 13 patients. However, the presence of a therapy sensitizing variant only led to consideration of a biomarker-directed therapy in 6 (10%) out of 61 patients. Conclusions: Overall, CGP of non-myeloid hematologic malignancies identified clinically significant variants in 72% of patients and resulted in a change in management in 22% of patients. Full article

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10 pages, 999 KiB

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

Viewed by 1362

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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11 pages, 619 KiB

Open AccessEditor’s ChoiceArticle

Padua Prediction Score and Hospital-Acquired Proximal and Isolated Distal Deep Vein Thrombosis in Symptomatic Patients

by Michelangelo Sartori, Miriam Fiocca, Mario Soldati, Laura Borgese, Elisabetta Favaretto and Benilde Cosmi

Hematol. Rep. 2024, 16(4), 568-578; https://doi.org/10.3390/hematolrep16040055 - 25 Sep 2024

Viewed by 1579

Abstract

Background: Hospital-acquired deep vein thrombosis (DVT) is an important cause of morbidity and mortality. Objectives: The purpose of this study was to evaluate the prevalence of proximal lower limb DVT and isolated distal DVT (IDDVT) and their relationship to the Padua Prediction Score [...] Read more.

Background: Hospital-acquired deep vein thrombosis (DVT) is an important cause of morbidity and mortality. Objectives: The purpose of this study was to evaluate the prevalence of proximal lower limb DVT and isolated distal DVT (IDDVT) and their relationship to the Padua Prediction Score (PPS) in acutely ill, hospitalized patients. Methods: In a single-center cross-sectional study, all inpatients from medical departments with suspected lower-extremity DVT were evaluated with whole-leg ultrasonography during 183 days from 2016 to 2017. Results: Among the 505 inpatients (age 78.0 ± 13.3, females 59.2%) from medical departments, 204 (40.2%) had PPS ≥ 4, but only 54.4% of them underwent pharmacological thrombo-prophylaxis. Whole-leg ultrasonography detected 47 proximal DVTs (9.3%) and 65 IDDVTs (12.8%). Proximal DVT prevalence was higher in patients with high PPS vs. those with low PPS (12.7% vs. 7.0% p = 0.029, respectively), whereas IDDVT prevalence was similar in patients with high and low PPS (14.7% vs. 11.6% p = 0.311, respectively). The area under the receiver operating curve (AUC) for the PPS was 0.62 ± 0.03 for all DVTs, 0.64 ± 0.04 for proximal DVTs, and 0.58 ± 0.04 for IDDVTs. Conclusions: In hospitalized patients, IDDVT had similar prevalence regardless of PPS risk stratification. Adherence to thrombo-prophylaxis in patients was still far from optimal. Full article

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9 pages, 563 KiB

Open AccessEditor’s ChoiceCase Report

How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency

by Sara Tama-Shekan, Valeria Moreno, Ludovic Saba and Chakra P. Chaulagain

Hematol. Rep. 2024, 16(3), 559-567; https://doi.org/10.3390/hematolrep16030054 - 31 Aug 2024

Cited by 1 | Viewed by 2125

Abstract

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management [...] Read more.

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder. Methods: A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases. Results: Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the PKLR gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the PKLR gene when making therapeutic decisions about starting a patient on mitapivat. Conclusions: While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat. Full article

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17 pages, 1150 KiB

Open AccessEditor’s ChoiceReview

Hemophagocytic Lymphohistiocytosis Triggered by Herpes Simplex Virus 1 and 2: A Narrative Review

by Andria Papazachariou and Petros Ioannou

Hematol. Rep. 2024, 16(3), 487-503; https://doi.org/10.3390/hematolrep16030047 - 26 Jul 2024

Cited by 2 | Viewed by 1860

Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical [...] Read more.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical features in cases associated with herpes simplex virus 1 and 2 remain underexplored. This study aimed to review all previously described cases of HSV-1 or -2-triggered HLH and provide information about this syndrome’s epidemiology, microbiology, clinical characteristics, treatment, and outcomes. Methods: A narrative review was performed based on a search in PubMed, the Cochrane Library, and Scopus. Studies published until 27 April 2024 providing relevant data for HLH due to HSV 1 and 2 in humans were included. Results: We identified 29 eligible studies reporting HLH due to HSV 1 and 2, involving 34 patients. Half of them were adults, and half were neonates. Fever and splenomegaly were the most common clinical findings. Most patients were diagnosed with HSV-1 (64.7%), with PCR being the primary diagnostic method. The median duration of in-hospital treatment was 21 days, with acyclovir and steroids being the mainstays of therapy. The overall mortality rate was 41.2%, and AST levels emerged as an independent predictor of mortality. Conclusions: Our findings underscore the need for heightened awareness surrounding HLH triggered by HSV 1 and 2 and the importance of prompt diagnosis and tailored treatment approaches. Full article

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14 pages, 649 KiB

Open AccessEditor’s ChoiceReview

Blood Microbiota and Its Products: Mechanisms of Interference with Host Cells and Clinical Outcomes

by Luigi Santacroce, Ioannis Alexandros Charitos, Marica Colella, Raffaele Palmirotta and Emilio Jirillo

Hematol. Rep. 2024, 16(3), 440-453; https://doi.org/10.3390/hematolrep16030043 - 6 Jul 2024

Cited by 1 | Viewed by 2212

Abstract

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field [...] Read more.

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field microscopy, fluorescent in situ hybridization, flow cytometry, and electron microscopy, so-called microbiota have been detected in the blood. Conversely, others have reported no evidence of a common blood microbiota. Then, it was hypothesized that blood microbiota may derive from distant sites, e.g., the gut or external contamination of blood samples. Alteration of the blood microbiota’s equilibrium may lead to dysbiosis and, in certain cases, disease. Cardiovascular, respiratory, hepatic, kidney, neoplastic, and immune diseases have been associated with the presence of Gram-positive and Gram-negative bacteria and/or their products in the blood. For instance, lipopolysaccharides (LPSs) and endotoxins may contribute to tissue damage, fueling chronic inflammation. Blood bacteria can interact with immune cells, especially with monocytes that engulf microorganisms and T lymphocytes via spontaneous binding to their membranes. Moreover, LPSs, extracellular vesicles, and outer membrane vesicles interact with red blood cells and immune cells, reaching distant organs. This review aims to describe the composition of blood microbiota in healthy individuals and those with disease conditions. Furthermore, special emphasis is placed on the interaction of blood microbiota with host cells to better understand disease mechanisms. Full article

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23 pages, 707 KiB

Open AccessEditor’s ChoiceReview

Treatment of Immune Thrombocytopenia: Contextualization from a Historical Perspective

by Daniel Martínez-Carballeira, Ángel Bernardo, Alberto Caro, Inmaculada Soto and Laura Gutiérrez

Hematol. Rep. 2024, 16(3), 390-412; https://doi.org/10.3390/hematolrep16030039 - 26 Jun 2024

Cited by 2 | Viewed by 3108

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and inadequate production in [...] Read more.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and inadequate production in the bone marrow. In this article, we review the treatment of ITP from a historical perspective, discussing first line and second line treatments, and management of refractory disease. Full article

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15 pages, 526 KiB

Open AccessEditor’s ChoiceReview

Neutropenia in Childhood—A Narrative Review and Practical Diagnostic Approach

by Georgios Katsaras, Silouani Koutsi, Evdokia Psaroulaki, Dimitra Gouni and Pelagia Tsitsani

Hematol. Rep. 2024, 16(2), 375-389; https://doi.org/10.3390/hematolrep16020038 - 16 Jun 2024

Cited by 3 | Viewed by 3796

Abstract

Neutropenia refers to a decrease in the absolute neutrophil count according to age and race norms and poses a common concern in pediatric practice. Neutrophils serve as host defenders and act crucially in acute inflammation procedures. In this narrative review, we systematically present [...] Read more.

Neutropenia refers to a decrease in the absolute neutrophil count according to age and race norms and poses a common concern in pediatric practice. Neutrophils serve as host defenders and act crucially in acute inflammation procedures. In this narrative review, we systematically present causes of neutropenia in childhood, mainly adopting the pathophysiological classification of Frater, thereby studying (1) neutropenia with reduced bone marrow reserve, (2) secondary neutropenia with reduced bone marrow reserve, and (3) neutropenia with normal bone marrow reserve. Different conditions in each category are thoroughly discussed and practically approached from the clinician’s point of view. Secondary mild to moderate neutropenia is usually benign due to childhood viral infections and is expected to resolve in 2–4 weeks. Bacterial and fungal agents are also associated with transient neutropenia, although fever with severe neutropenia constitutes a medical emergency. Drug-induced and immune neutropenias should be suspected following a careful history and a detailed clinical examination. Cytotoxic chemotherapies treating malignancies are responsible for severe neutropenia and neutropenic shock. Rare genetic neutropenias usually manifest with major infections early in life. Our review of taxonomies clinical findings and associates them to specific neutropenia disorders. We consequently propose a practical diagnostic algorithm for managing neutropenic children. Full article

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9 pages, 1255 KiB

Open AccessEditor’s ChoiceCase Report

Complications of Brentuximab Therapy in Patients with Hodgkin’s Lymphoma and Concurrent Autoimmune Pathology—A Case Series

by Oana Diana Preda, Sorina Bădeliță, Iulia Ursuleac, Ruxandra Maria Irimia, Sonia Balanica, Monica Cojocaru, Cristina Cotruta, Camelia Dobrea and Daniel Coriu

Hematol. Rep. 2024, 16(2), 299-307; https://doi.org/10.3390/hematolrep16020030 - 20 May 2024

Cited by 1 | Viewed by 1355

Abstract

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin’s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn’s disease, vitiligo, type I diabetes, and minimal change [...] Read more.

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin’s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn’s disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin’s lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care. Full article

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12 pages, 1071 KiB

Open AccessEditor’s ChoiceArticle

Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study

by David Michonneau, Raynier Devillier, Mikko Keränen, Marie Thérèse Rubio, Malin Nicklasson, Hélène Labussière-Wallet, Martin Carre, Anne Huynh, Elisabet Viayna, Montserrat Roset, Jonathan Finzi, Minja Pfeiffer, Daniel Thunström, Núria Lara, Lorenzo Sabatelli, Patrice Chevallier and Maija Itälä-Remes

Hematol. Rep. 2024, 16(2), 283-294; https://doi.org/10.3390/hematolrep16020028 - 6 May 2024

Cited by 1 | Viewed by 1954

Abstract

Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, [...] Read more.

Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II–IV aGVHD after their first HSCT (January 2016–June 2017). From 13 participating centers, 151 patients were included. The median (Q1, Q3) age at HSCT was 56 (45, 62) years old. One line of aGVHD treatment was received by 47.7%, and the most common first-line treatment was methylprednisolone (alone or in a combination regimen, 74.2%; monotherapy, 25.8%). Among patients treated with methylprednisolone, 79.5% achieved a complete or partial response. The median (Q1, Q3) number of treatment lines was 2.0 (1.0, 3.0). The median (Q1, Q3) time to obtain an aGVHD diagnosis from transplant was 29.5 (21.0, 44.0) days, and 14.5 (7.0, 34.0) days to achieve the best response for 110 evaluable patients. At 6 and 12 months, 53.6% and 49.0%, respectively, achieved a complete response. Chronic GVHD occurred in 37.7% of patients, and aGVHD reoccurred in 26.5%. Following aGVHD diagnosis, mortality rates were 30.0% at 6 months and 37.3% at 12 months. Findings from this study demonstrate a continuing unmet need for new therapies that control aGVHD and improve mortality. Full article

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13 pages, 887 KiB

Open AccessEditor’s ChoiceReview

Current Therapeutic Sequencing in Chronic Lymphocytic Leukemia

by Samir Mouhssine, Nawar Maher, Sreekar Kogila, Claudio Cerchione, Giovanni Martinelli and Gianluca Gaidano

Hematol. Rep. 2024, 16(2), 270-282; https://doi.org/10.3390/hematolrep16020027 - 30 Apr 2024

Cited by 2 | Viewed by 2607

Abstract

The treatment landscape of chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults, is constantly changing. CLL patients can be divided into three risk categories, based on their IGHV mutational status and the occurrence of TP53 disruption and/or complex karyotype. For the [...] Read more.

The treatment landscape of chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults, is constantly changing. CLL patients can be divided into three risk categories, based on their IGHV mutational status and the occurrence of TP53 disruption and/or complex karyotype. For the first-line treatment of low- and intermediate-risk CLL, both the BCL2 inhibitor venetoclax plus obinutuzumab and the second generation BTK inhibitors (BTKi), namely acalabrutinib and zanubrutinib, are valuable and effective options. Conversely, venetoclax-based fixed duration therapies have not shown remarkable results in high-risk CLL patients, while continuous treatment with acalabrutinib and zanubrutinib displayed favorable outcomes, similar to those obtained in TP53 wild-type patients. The development of acquired resistance to pathway inhibitors is still a clinical challenge, and the optimal treatment sequencing of relapsed/refractory CLL is not completely established. Covalent BTKi-refractory patients should be treated with venetoclax plus rituximab, whereas venetoclax-refractory CLL may be treated with second generation BTKi in the case of early relapse, while venetoclax plus rituximab might be used if late relapse has occurred. On these grounds, here we provide an overview of the current state-of-the-art therapeutic algorithms for treatment-naïve patients, as well as for relapsed/refractory disease. Full article

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11 pages, 1460 KiB

Open AccessEditor’s ChoiceReview

A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

by Anna Candoni and Gabriele Coppola

Hematol. Rep. 2024, 16(2), 244-254; https://doi.org/10.3390/hematolrep16020024 - 18 Apr 2024

Cited by 23 | Viewed by 5785

Abstract

Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents [...] Read more.

Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin–KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib. Full article

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16 pages, 604 KiB

Open AccessEditor’s ChoiceReview

Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective

by Daniel Martínez-Carballeira, Ángel Bernardo, Alberto Caro, Inmaculada Soto and Laura Gutiérrez

Hematol. Rep. 2024, 16(2), 204-219; https://doi.org/10.3390/hematolrep16020021 - 3 Apr 2024

Cited by 9 | Viewed by 8924

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in the platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and impaired central [...] Read more.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in the platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and impaired central megakaryopoiesis and platelet production in the bone marrow. Here, we intend to contextualize the current knowledge on the pathophysiology, terminology, epidemiology, clinical manifestations, diagnosis, and prognosis of ITP from a historical perspective and the first references to the never-stopping garnering of knowledge about this entity. We highlight the necessity to better understand ITP in order to be able to provide ITP patients with personalized treatment options, improving disease prognosis and reducing the incidence or frequency of refractoriness. Full article

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11 pages, 3094 KiB

Open AccessEditor’s ChoiceReview

Ophthalmic Manifestations in Patients with Blood Malignancies

by Costanza Rossi, Alessandro Buizza, Giuseppe Alessio, Massimiliano Borselli, Andrea Taloni, Adriano Carnevali, Giovanna Carnovale Scalzo, Andrea Lucisano, Vincenzo Scorcia and Giuseppe Giannaccare

Hematol. Rep. 2024, 16(2), 193-203; https://doi.org/10.3390/hematolrep16020020 - 28 Mar 2024

Cited by 2 | Viewed by 2042

Abstract

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 [...] Read more.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life. Full article

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13 pages, 1284 KiB

Open AccessEditor’s ChoiceReview

Drug–Drug Interactions of FXI Inhibitors: Clinical Relevance

by Nicola Ferri, Elisa Colombo and Alberto Corsini

Hematol. Rep. 2024, 16(1), 151-163; https://doi.org/10.3390/hematolrep16010016 - 21 Mar 2024

Cited by 8 | Viewed by 3325

Abstract

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian [...] Read more.

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug–drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa. Full article

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7 pages, 1177 KiB

Open AccessEditor’s ChoiceCase Report

Uncommon Presentation of Sarcoidosis with Severe Thrombocytopenia and Hemorrhagic Diathesis

by Dorela Lame, Michelangelo Pianelli, Shahram Kordasti, Erika Morsia, Attilio Olivieri and Antonella Poloni

Hematol. Rep. 2024, 16(1), 125-131; https://doi.org/10.3390/hematolrep16010013 - 4 Mar 2024

Cited by 1 | Viewed by 2198

Abstract

Sarcoidosis, a multi-organ system disease, often presents insidiously. Thrombocytopenia in sarcoidosis is frequent because of hypersplenism, granulomas infiltrating the bone marrow, or immune thrombocytopenia (ITP). The diagnosis of ITP relies on exclusionary criteria, given the absence of a definitive laboratory diagnostic feature. In [...] Read more.

Sarcoidosis, a multi-organ system disease, often presents insidiously. Thrombocytopenia in sarcoidosis is frequent because of hypersplenism, granulomas infiltrating the bone marrow, or immune thrombocytopenia (ITP). The diagnosis of ITP relies on exclusionary criteria, given the absence of a definitive laboratory diagnostic feature. In the era prior to modern ITP management, sarcoidosis-associated ITP was known to manifest severely, often showing resistance to treatment and an increased risk of mortality. In this case, we present a young male who was admitted to a district hospital’s emergency room, displaying symptoms of hematuria, gingival bleeding, and a petechial rash. Blood tests revealed severe thrombocytopenia with a platelet count of 0, while all other metabolic and serological exams returned normal results. Infectious and autoimmune causes were ruled out, and a bone marrow examination excluded any hematological disorder. Initial management, including platelet transfusion and presumptive treatment for ITP with dexamethasone and Human Immunoglobulin IV (IVIG), failed to improve the patient’s platelet count or alleviate the hemorrhagic diathesis. Second-line therapy with Rituximab and Methylprednisolone was initiated with no benefit. Considering the hemorrhagic signs and the delayed response of Rituximab, we shifted to third-line therapy with Romiplostim at the maximal dose and continued Methylprednisolone. The platelet count recovered completely after the second Romiplostim administration (over 350 × 10⁹ platelets/L) and Methylprednisolone was rapidly tapered. To further study the causes of thrombocytopenia a total body CT scan was performed and it identified non-homogeneously hypodense tissue in the bilateral hilar area extending medially to the subcarinal area, suggesting possible lymphatic origin and raising suspicion of sarcoidosis. Further investigations, including Angiotensin Converting Enzyme (ACE) titration, bronchoscopy, bronchoalveolar lavage, and EndoBronchial UltraSound-guided TransBronchial Needle Aspiration (EBUS-TBNA), confirmed the diagnosis of sarcoidosis. Despite a mild restrictive insufficiency noted in spirometry, the patient remained asymptomatic with only a mild respiratory insufficiency, and hence, was enlisted for follow-up. As for the ITP, the platelet count remained normal over a year. Notably, while sarcoidosis onset often predates ITP onset by an average of 48 months, in our case the onset of the two diseases was simultaneously. Our case adds valuable information to the limited body of knowledge regarding the treatment of sarcoidosis-associated ITP. Full article

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11 pages, 1047 KiB

Open AccessEditor’s ChoiceArticle

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine

by Eri Takada, Nobuhiko Nakamura, Yuto Kaneda, Kenji Fukuno, Shin Lee, Kei Fujita, Tetsuji Morishita, Yoshikazu Ikoma, Takuro Matsumoto, Hiroshi Nakamura, Junichi Kitagawa, Nobuhiro Kanemura, Senji Kasahara, Takeshi Hara, Hisashi Tsurumi and Masahito Shimizu

Hematol. Rep. 2024, 16(1), 114-124; https://doi.org/10.3390/hematolrep16010012 - 28 Feb 2024

Cited by 1 | Viewed by 1395

Abstract

Background: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. Methods: This [...] Read more.

Background: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. Methods: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. Results: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3–4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. Conclusion: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA. Full article

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8 pages, 2192 KiB

Open AccessEditor’s ChoiceCase Report

Primary Bone Lymphoma of the Scapula

by Josip Lovaković, Inga Mandac Smoljanović, Andro Matković and Tomislav Smoljanović

Hematol. Rep. 2024, 16(1), 106-113; https://doi.org/10.3390/hematolrep16010011 - 28 Feb 2024

Cited by 1 | Viewed by 2047

Abstract

Primary bone lymphoma of the scapula is a rare tumor that usually causes local pain. The presented patient suffered for two years from paresthesia, tingling, numbness, and edema of the little and ring fingers. The 45-year-old man underwent several radiological and neurological assessments [...] Read more.

Primary bone lymphoma of the scapula is a rare tumor that usually causes local pain. The presented patient suffered for two years from paresthesia, tingling, numbness, and edema of the little and ring fingers. The 45-year-old man underwent several radiological and neurological assessments of the palm, elbow, and neck before radiographs revealed a tumor of the left shoulder. Once diffuse large B-cell lymphoma was confirmed, immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and methylprednisolone (R-CHOP) started. The treatment was accompanied by antiviral treatment with lamivudine due to positive hepatitis B virus serology, specifically anti-HBs (hepatitis B surface) antibody, total anti-HBc (hepatitis B core) antibody, and anti-HBe (hepatitis B e antigen) antibody, together with bisphosphonate treatment for the prevention of bone resorption. Once immunochemotherapy was finished, the treatment was supplemented by radiotherapy of the shoulder. After more than three years of remission, the patient had an ischemic stroke manifesting with right-sided hemiparesis. Following physical therapy, the patient is currently in the process of evaluation for thrombophilia, as well as further cardiac assessment due to the positive transcranial Doppler bubble test, setting high suspicion for the presence of patent foramen ovale. Full article

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8 pages, 987 KiB

Open AccessEditor’s ChoiceCase Report

Successful Bone Marrow Transplantation in a Patient with Acute Myeloid Leukemia Developed from Severe Congenital Neutropenia Using Modified Chemotherapy and Conditioning Regimen for Leukemia

by Risa Matsumura, Shinji Mochizuki, Yusuke Morishita, Hiroko Hayakawa, Shuhei Karakawa, Hiroshi Kawaguchi, Satoshi Okada, Nobuyuki Hyakuna and Masao Kobayashi

Hematol. Rep. 2024, 16(1), 98-105; https://doi.org/10.3390/hematolrep16010010 - 26 Feb 2024

Cited by 1 | Viewed by 2200

Abstract

Severe congenital neutropenia (SCN) is characterized by chronic neutropenia with recurrent infections from early infancy and a predisposition to myelodysplastic syndrome/acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with SCN who develop myelodysplastic syndrome/AML. [...] Read more.

Severe congenital neutropenia (SCN) is characterized by chronic neutropenia with recurrent infections from early infancy and a predisposition to myelodysplastic syndrome/acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with SCN who develop myelodysplastic syndrome/AML. We report an 8-year-old girl with SCN carrying an ELANE mutation that had been refractory to granulocyte colony-stimulating factor. The patient experienced recurrent infections and then developed AML. The counts of leukemic blasts that harbored both CSF3R and RUNX1 mutations spontaneously decreased with antimicrobial therapy, leading to partial remission. After AML recurrence, HSCT was successfully performed using modified chemotherapy and a conditioning regimen. Serial donor lymphocyte infusions against mixed chimerism induced complete donor chimerism over 4 years without any infections or AML relapse. This case suggests the importance of carefully managing neutropenia-related infections, leukemia progression, and HSCT in patients with SCN developing AML. Full article

(This article belongs to the Special Issue Diagnosis and Management of Acute Leukemia(AML, ALL): Drafting from Molecular Mechanisms to Clinical Practice)

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13 pages, 1758 KiB

Open AccessEditor’s ChoiceArticle

Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study

by Emanuele Cencini, Natale Calomino, Marta Franceschini, Andreea Dragomir, Sara Fredducci, Beatrice Esposito Vangone, Giulia Lucco Navei, Alberto Fabbri and Monica Bocchia

Hematol. Rep. 2024, 16(1), 50-62; https://doi.org/10.3390/hematolrep16010006 - 18 Jan 2024

Cited by 3 | Viewed by 2924

Abstract

Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials. We investigated 73 consecutive MCL patients managed from 2006 to 2020. For younger patients <65 years [...] Read more.

Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials. We investigated 73 consecutive MCL patients managed from 2006 to 2020. For younger patients <65 years old, the median PFS was 72 months and we reported a 2-year, 5-year, and 10-year PFS of 73%, 62%, and 41%; median OS was not reached and we reported a 2-year, 5-year, and 10-year OS of 88%, 82%, and 66%. For patients aged 75 years or older, the median PFS was 36 months and we reported a 2-year, 5-year, and 10-year PFS of 52%, 37%, and 37%; median OS was not reached and we reported a 2-year, 5-year, and 10-year OS of 72%, 55%, and 55%. The median PFS was significantly reduced for patients treated between 2006 and 2010 compared to patients treated between 2011 and 2015 (p = 0.04). Interestingly, there was a trend towards improved OS for patients treated between 2016 and 2020 compared to between 2006 and 2010 and between 2011 and 2015 (5-year OS was 91%, 44%, and 33%). These findings could be due to the introduction of BR as a first-line regimen for elderly patients and to the introduction of ibrutinib as a second-line regimen. Full article

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8 pages, 998 KiB

Open AccessEditor’s ChoiceCase Report

Manifestation of Pancytopenia Associated with COVID-19 as Paroxysmal Nocturnal Hemoglobinuria (PNH) and Aplastic Anemia (AA)

by Jeff Justin Aguilar, Vikram Dhillon and Suresh Balasubramanian

Hematol. Rep. 2024, 16(1), 42-49; https://doi.org/10.3390/hematolrep16010005 - 17 Jan 2024

Cited by 1 | Viewed by 3033

Abstract

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases illustrate a common pathway whereby a viral trigger causes the clonal expansion of a hematological disorder. Although [...] Read more.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases illustrate a common pathway whereby a viral trigger causes the clonal expansion of a hematological disorder. Although the association of both cases with COVID-19 is temporal and COVID-19 may be an incidental diagnosis, the growing evidence related to the hematological effects of SARS-CoV-2 infection highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Congenital and Acquired Haemorrhagic Disorders, Thromboembolic Disease and Platelet Disorders)

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10 pages, 256 KiB

Open AccessEditor’s ChoiceReview

Emerging Role of [¹⁸F]FLT PET/CT in Lymphoid Malignancies: A Review of Clinical Results

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

Hematol. Rep. 2024, 16(1), 32-41; https://doi.org/10.3390/hematolrep16010004 - 11 Jan 2024

Cited by 7 | Viewed by 1953

Abstract

Fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) is nowadays the leading positron emission tomography (PET) tracer for routine clinical work-ups in hematological malignancies; however, it is limited by false positive findings. Notably, false positives can occur in inflammatory and infective cases or in necrotic tumors [...] Read more.

Fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) is nowadays the leading positron emission tomography (PET) tracer for routine clinical work-ups in hematological malignancies; however, it is limited by false positive findings. Notably, false positives can occur in inflammatory and infective cases or in necrotic tumors that are infiltrated by macrophages and other inflammatory cells. In this context, 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) has been shown to be a promising imaging biomarker of hematological malignant cell proliferation. In this review, a total of 15 papers were reviewed to collect literature data regarding the clinical application of [¹⁸F]FLT PET/CT in hematological malignancies. This imaging modality seems to be a suitable tool for noninvasive assessment of tumor grading, also showing a correlation with Ki-67 immunostaining. Moreover, [¹⁸F]FLT PET/CT demonstrated high sensitivity in detecting aggressive lymphoma lesions, especially when applying a standardized uptake value (SUV) cutoff of 3. At baseline, the potential of [¹⁸F]FLT imaging as a predictive tool is demonstrated by the low tracer uptake in patients with a complete response. However, its use is limited in evaluating bone diseases due to its high physiological uptake in bone marrow. Interim [¹⁸F]FLT PET/CT (iFLT) has the potential to identify high-risk patients with greater precision than [¹⁸F]FDG PET/CT, optimizing risk-adapted therapy strategies. Moreover, [¹⁸F]FLT uptake showed a greater ability to differentiate tumor from inflammation compared to [¹⁸F]FDG, allowing the reduction of false-positive findings and making the first one a more selective tracer. Finally, FLT emerges as a superior independent predictor of PFS and OS compared to FDG and ensures a reliable early response assessment with greater accuracy and predictive value. Full article

(This article belongs to the Special Issue Comparison between 18F-FDG and Alternative Tracers for the Assessment of Hematological Ma-Lignancies)

10 pages, 4859 KiB

Open AccessEditor’s ChoiceCase Report

Plasmacytoma in the Maxillary Jaw: A Diagnostic and Therapeutic Challenge

by Sara Bernardi, Serena Bianchi, Ettore Lupi, Davide Gerardi, Guido Macchiarelli and Giuseppe Varvara

Hematol. Rep. 2024, 16(1), 22-31; https://doi.org/10.3390/hematolrep16010003 - 4 Jan 2024

Cited by 6 | Viewed by 1938

Abstract

Plasmacytoma is a neoplastic disorder originating from plasma cells, with bone and soft tissue being common sites of manifestation. This report presents the clinical and radiological findings of a 65-year-old female patient who presented with an exophytic lesion in the upper right lateral [...] Read more.

Plasmacytoma is a neoplastic disorder originating from plasma cells, with bone and soft tissue being common sites of manifestation. This report presents the clinical and radiological findings of a 65-year-old female patient who presented with an exophytic lesion in the upper right lateral incisor region. The lesion appeared as a unilocular radiotransparent area in imaging tests. Following an excisional biopsy, histological and immunohistochemical evaluations confirmed the presence of mature plasmacellular elements and small infiltrates of B and T lymphocytes. The patient did not exhibit systemic manifestations of multiple myeloma. Surgical intervention, in the form of enucleation of the lesion combined with root canal treatment and apicoectomy, was performed. This case underscores the rare occurrence of plasmacytoma in the jaw region and highlights the importance of surgical management in cases where structural damage or functional impairment is present. Further research on novel treatment approaches is also mentioned, including targeted therapies, immunomodulatory agents, and monoclonal antibodies. The patient is currently under the care of a hematologist for further investigation and the choice of the most appropriate therapy. Full article

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11 pages, 1799 KiB

Open AccessEditor’s ChoiceReview

Blastic Plasmocytoid Dendritic Cell Neoplasm (BPDCN): Clinical Features and Histopathology with a Therapeutic Overview

by Gerardo Cazzato, Marialessandra Capuzzolo, Emilio Bellitti, Giovanni De Biasi, Anna Colagrande, Katia Mangialardi, Francesco Gaudio and Giuseppe Ingravallo

Hematol. Rep. 2023, 15(4), 696-706; https://doi.org/10.3390/hematolrep15040070 - 8 Dec 2023

Cited by 5 | Viewed by 2470

Abstract

Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCNs) are a rare, highly aggressive hematological malignant neoplasm that primarily involve the skin, bone marrow, lymph nodes and even extra-nodal sites. The rarity and relative poor description of cases in the literature make it necessary to review [...] Read more.

Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCNs) are a rare, highly aggressive hematological malignant neoplasm that primarily involve the skin, bone marrow, lymph nodes and even extra-nodal sites. The rarity and relative poor description of cases in the literature make it necessary to review and further studies that deeply investigate this entity not only in a histopathological but also molecular field. In August–September 2023, we searched MEDLINE, PubMed and Scopus for randomized controlled trials (RCTs), narrative and systematic reviews, meta-analyses, observational studies (either longitudinal or retrospective), and case series published in English in the last 25 years using the keywords BPDCN, PDCs, Blastic NK-cell lymphoma, agranular CD4+ NK leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm/tumor. Despite the progress made in recent years in the diagnosis and biological understanding of the disease, until 2018 there was no clear consensus regarding its treatment and the main therapeutic schemes used were based on chemotherapy regimens already used in the treatment of lymphomas, acute lymphoblastic leukemia (ALL) and/or acute myeloid leukemia (AML). In this narrative review, we address the definition and epidemiological features of BPDCN, provide the different theories on the etiopathogenesis with particular attention to the presumed cell of origin, discuss the main clinical manifestations that provide a sign of its presence, summarize the main histopathological and immunophenotypic characteristics with special attention to the most important markers, and finally, we provide some of the most effective information on the therapeutic treatment modalities of BPDCN. Full article

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12 pages, 1268 KiB

Open AccessEditor’s ChoiceArticle

Platelet Microvesicles, Inflammation, and Coagulation Markers: A Pilot Study

by Antonio Gidaro, Alessandro Palmerio Delitala, Roberto Manetti, Sonia Caccia, Mark J. Soloski, Giorgio Lambertenghi Deliliers, Dante Castro, Mattia Donadoni, Arianna Bartoli, Giuseppe Sanna, Luigi Bergamaschini and Roberto Castelli

Hematol. Rep. 2023, 15(4), 684-695; https://doi.org/10.3390/hematolrep15040069 - 4 Dec 2023

Cited by 4 | Viewed by 2081

Abstract

Background: Platelet “Microvesicles” (MVs) are studied for their role in blood coagulation and inflammation. The study aimed to establish if MVs are related to age, plasma levels of inflammation, coagulation, and fibrinolysis markers in healthy individuals. Methods: We prospectively enrolled volunteers aged over [...] Read more.

Background: Platelet “Microvesicles” (MVs) are studied for their role in blood coagulation and inflammation. The study aimed to establish if MVs are related to age, plasma levels of inflammation, coagulation, and fibrinolysis markers in healthy individuals. Methods: We prospectively enrolled volunteers aged over 18 years. MVs, plasma levels of C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 17 (IL-17), and transforming growth factor β (TGF-β), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), homocysteine, factor VII (FVII), thrombin activatable fibrinolysis inhibitor (TAFI), and Protein S were tested. Results: A total of 246 individuals (median age 65 years (“IQR”54–72)) were evaluated. Both univariate analysis and logistic regression models showed that MVs positively correlate with age, CRP, IL-6, IL-10, IL-17, TGF-β, fibrinogen, PAI-1, VWF, FVII, and homocysteine, while inversely correlating with TAFI and Protein S. The ROC curve analysis performed to identify a cut off for MV values (700 kMP) showed a good accuracy with over-range cytokines fibrinolysis factor and coagulation markers. Conclusions: To the best of our knowledge, this study is the first to correlate MVs with an entire panel of cardiovascular risk factors in healthy individuals. A future possible role of MVs in screening exams is suggested. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Congenital and Acquired Haemorrhagic Disorders, Thromboembolic Disease and Platelet Disorders)

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8 pages, 2698 KiB

Open AccessEditor’s ChoiceCase Report

Angioimmunoblastic T-Cell Lymphoma after Treatment of Classic Hodgkin Lymphoma: A Case Report

by Ken Tanaka, Hiroaki Miyoshi, Yusuke Yamashita, Ryuta Iwamoto, Yuma Yokoya, Yuichi Tochino, Fumiko Arakawa, Shinobu Tamura, Shin-Ichi Murata, Takashi Sonoki and Koichi Ohshima

Hematol. Rep. 2023, 15(4), 662-669; https://doi.org/10.3390/hematolrep15040067 - 25 Nov 2023

Cited by 2 | Viewed by 1706

Abstract

We report a case of a 24-year-old man who developed angioimmunoblastic T-cell lymphoma (AITL) after treatment for refractory lymphocyte-rich classic Hodgkin lymphoma (LR-CHL). This patient was treated with the BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) protocol for LR-CHL but progressed before completing [...] Read more.

We report a case of a 24-year-old man who developed angioimmunoblastic T-cell lymphoma (AITL) after treatment for refractory lymphocyte-rich classic Hodgkin lymphoma (LR-CHL). This patient was treated with the BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) protocol for LR-CHL but progressed before completing chemotherapy. The pathological imaging showed the typical findings of LR-CHL at the first onset and first progression. Rescue chemotherapy and high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT) were performed for refractory LR-CHL, and complete remission was achieved. However, the recurrence was suspected 6 months after AHSCT. The pathological findings of the lymph node biopsy at this time were different from those of the previous two lymph node biopsies, demonstrating findings of AITL. The finding of the immunohistochemical staining and polymerase chain reaction results supported the diagnosis. Although it has been reported that the risk for the development of non-Hodgkin lymphoma after treatment for Hodgkin lymphoma is increased, most are B-cell lymphomas, and few cases of AITL have been reported. AITL is a type of peripheral T-cell lymphoma that generally occurs in middle-aged and elderly people and that rarely occurs in young people. Here, we were able to make an accurate diagnosis by performing re-examination even when recurrence of LR-CHL was suspected. As there are no detailed case reports of AITL developing into secondary non-Hodgkin lymphoma, here we report on an identified case. Full article

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17 pages, 681 KiB

Open AccessEditor’s ChoiceReview

Association of microRNA Polymorphisms with Toxicities Induced by Methotrexate in Children with Acute Lymphoblastic Leukemia

by Vasiliki Karpa, Kallirhoe Kalinderi, Liana Fidani and Athanasios Tragiannidis

Hematol. Rep. 2023, 15(4), 634-650; https://doi.org/10.3390/hematolrep15040065 - 20 Nov 2023

Cited by 5 | Viewed by 2017

Abstract

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary [...] Read more.

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5′-regulatory regions of genes. Recent studies have demonstrated a significant role of microRNAs (miRNAs) in the transport and metabolism of drugs and in the regulation of target genes. In the last few years, the number of annotated miRNAs has continually risen, in addition to the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects. Full article

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19 pages, 2791 KiB

Open AccessEditor’s ChoiceReview

Chimeric Antigen Receptor T Cell Therapy in Acute Myeloid Leukemia: Trials and Tribulations

by Swati Garg, Wei Ni, James D. Griffin and Martin Sattler

Hematol. Rep. 2023, 15(4), 608-626; https://doi.org/10.3390/hematolrep15040063 - 12 Nov 2023

Cited by 3 | Viewed by 3513

Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. [...] Read more.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is now being investigated in AML. Initial clinical trials have been disappointing in AML, and we review current strategies to improve efficacy for CAR approaches. The extensive number of clinical trials targeting different antigens likely reflects the genetic heterogeneity of AML. The limited number of patients reported in multiple early clinical studies makes it difficult to draw conclusions about CAR safety, but it does suggest that the efficacy of this approach in AML lags behind the success observed in B cell malignancies. There is a clear need not only to improve CAR design but also to identify targets in AML that show limited expression in normal myeloid lineage cells. Full article

(This article belongs to the Special Issue Cell Therapies in Hematology: Current Updates and Perspectives)

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14 pages, 468 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Costs per Responder in US Adults with Paroxysmal Nocturnal Hemoglobinuria with a Suboptimal Response to Prior Eculizumab Treatment

by Jesse Fishman, Seri Anderson, Sandra E. Talbird and David Dingli

Hematol. Rep. 2023, 15(4), 578-591; https://doi.org/10.3390/hematolrep15040060 - 13 Oct 2023

Cited by 2 | Viewed by 3055

Abstract

European Society for Blood and Marrow Transplantation (EBMT) hematologic response categories comprehensively assess complement inhibitor responses in patients with paroxysmal nocturnal hemoglobinuria (PNH). Using data from the 16-week randomized controlled period of the phase 3 PEGASUS trial (N = 80), we estimated the [...] Read more.

European Society for Blood and Marrow Transplantation (EBMT) hematologic response categories comprehensively assess complement inhibitor responses in patients with paroxysmal nocturnal hemoglobinuria (PNH). Using data from the 16-week randomized controlled period of the phase 3 PEGASUS trial (N = 80), we estimated the treatment cost per responder by the EBMT response category for pegcetacoplan and eculizumab in adults with PNH and a suboptimal response to eculizumab. Average drug costs per responder, number needed to treat, and incremental drug costs per responder were estimated using dosages administered during the trial (base case). A US payer perspective (2020 US dollars) was used. Scenario analyses were conducted for various costs, dosages, treatment durations, patient populations, and settings. In total, 30 of 41 (73%) who switched to pegcetacoplan and 2 of 39 (5%) patients who continued eculizumab had a good, major, or complete response (good-to-complete responders) at Week 16. Average weekly drug costs per good-to-complete responder were USD 15,923 with pegcetacoplan and USD 216,100 with eculizumab; average weekly drug costs per patient were USD 11,651 and USD 11,082, respectively. Average drug costs per good-to-complete responder with pegcetacoplan were similar across complement inhibitor-naïve populations and were consistently lower than with eculizumab. Switching from eculizumab to pegcetacoplan allowed more patients with a suboptimal response to attain a good-to-complete response at lower costs. These results apply to patients with a suboptimal response to prior eculizumab treatment only. Full article

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12 pages, 1338 KiB

Open AccessEditor’s ChoiceArticle

Changes in Hematological and Hemorheological Parameters Following Mild COVID-19: A 4-Month Follow-Up Study

by Janina Bros, Lars Ibershoff, Emily Zollmann, Jonas Zacher, Fabian Tomschi, Hans-Georg Predel, Wilhelm Bloch and Marijke Grau

Hematol. Rep. 2023, 15(4), 543-554; https://doi.org/10.3390/hematolrep15040057 - 10 Oct 2023

Cited by 4 | Viewed by 2612

Abstract

Background: Coronavirus Disease 2019 (COVID-19) was described to affect red blood cells (RBC) in both severe and mild disease courses. The aim of this study was to investigate whether hematological and hemorheological changes that were previously described for COVID-19 patients after the acute [...] Read more.

Background: Coronavirus Disease 2019 (COVID-19) was described to affect red blood cells (RBC) in both severe and mild disease courses. The aim of this study was to investigate whether hematological and hemorheological changes that were previously described for COVID-19 patients after the acute infection state are still prominent after another 4 months to assess potential long-term effects. Methods: Hematological and RBC rheological parameters, including deformability and aggregation, were measured 41 days after infection in COVID-19 patients and non-COVID control (T0) and 4 months later in COVID-19 patients (T1). Results: The data confirm alterations in hematological parameters, mainly related to cell volume and hemoglobin concentration, but also reduced deformability and increased aggregation at T0 compared to control. While RBC deformability seems to have recovered, hemoglobin-related parameters and RBC aggregation were still impaired at T1. The changes were thus more pronounced in male COVID-19 patients. Conclusion: COVID-19-related changes of the RBC partly consist of several months and might be related to persistent symptoms reported by many COVID-19 patients. Full article

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11 pages, 571 KiB

Open AccessEditor’s ChoiceArticle

Real-World Clinical Characterisation of Polycythaemia Vera Patients from a Prospective Registry in Portugal: Is Resistance to Hydroxyurea a Reality?

by Maria Sarmento, Marta Duarte, Sandra Ponte, Juan Sanchez, Diana Roriz, Laura Fernandes, Maria José Monteiro Silva, Judite Pacheco, Gisela Ferreira, Jorge Freitas, Inês Costa and Daniel Brás

Hematol. Rep. 2023, 15(3), 532-542; https://doi.org/10.3390/hematolrep15030056 - 13 Sep 2023

Cited by 1 | Viewed by 2192

Abstract

Patients with polycythaemia vera (PV) are at increased risk of thrombosis and haemorrhages. Although hydroxyurea (HU) has been the frontline therapy for patients at high risk of vascular complications, about 25% of patients develop resistance/intolerance to this therapy. The aim of this non-interventional, [...] Read more.

Patients with polycythaemia vera (PV) are at increased risk of thrombosis and haemorrhages. Although hydroxyurea (HU) has been the frontline therapy for patients at high risk of vascular complications, about 25% of patients develop resistance/intolerance to this therapy. The aim of this non-interventional, multicentre cohort study was to understand the clinical characteristics and HU treatment response of Portuguese PV patients. HU resistance/intolerance was defined according to adjusted European LeukemiaNet (ELN) criteria. In total, 134 PV patients with a mean (SD) disease duration of 4.8 (5.0) years were included and followed up for 2 years. At baseline, most patients were ≥60 years old (83.2%), at high risk for thrombotic events (87.2%), and receiving HU therapy (79.1%). A total of 10 thrombotic events and 8 haemorrhagic events were reported, resulting in a 5-year probability of thrombo-haemorrhagic events of 17.2%. Haematocrit (p = 0.007), haemoglobin (p = 0.012) and MPN10 symptom score (12.0 (11.6) vs. 10.3 (9.1); p = 0.041) decreased significantly at the 24-month visit compared to baseline. Overall, 75.9% of patients met at least one of the adjusted ELN criteria for HU resistance, and 14.4% of patients remained on HU throughout the study. The results from this real-world study may help identify the subset of patients at higher risk for disease sequelae who may benefit from earlier second-line treatment. Full article

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11 pages, 912 KiB

Open AccessEditor’s ChoiceReview

How I Manage Chronic Lymphocytic Leukemia

by Patrice Nasnas, Claudio Cerchione, Gerardo Musuraca, Giovanni Martinelli and Alessandra Ferrajoli

Hematol. Rep. 2023, 15(3), 454-464; https://doi.org/10.3390/hematolrep15030047 - 1 Aug 2023

Cited by 6 | Viewed by 4576

Abstract

Chronic lymphocytic leukemia (CLL), is a hematologic malignancy characterized by the uncontrolled proliferation of mature B lymphocytes. CLL is the most prevalent leukemia in Western countries. Its presentation can range from asymptomatic with the incidental finding of absolute lymphocytosis on a routine blood [...] Read more.

Chronic lymphocytic leukemia (CLL), is a hematologic malignancy characterized by the uncontrolled proliferation of mature B lymphocytes. CLL is the most prevalent leukemia in Western countries. Its presentation can range from asymptomatic with the incidental finding of absolute lymphocytosis on a routine blood test, to symptomatic disease requiring immediate intervention. Prognosis of the disease is defined by the presence or absence of specific mutations such as TP53, chromosomal abnormalities such as del(17p), a type of IGHV mutational status, and elevation of B2M and LDH. Treatment of CLL in the United States and Europe has evolved over the recent years thanks to the development of targeted therapies. The standard of care has shifted from traditional chemoimmunotherapy approaches to targeted therapies including Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors, administered either as monotherapy or in combination with CD20 monoclonal antibodies. Several clinical trials have also recently evaluated combinations of BTKi and venetoclax and showed the combination to be well tolerated and able to induce deep remissions. Targeted therapies have a good safety profile overall; however, they also have unique toxicities that are important to recognize. Diarrhea, fatigue, arthralgia, infections, cytopenias, bleeding, and cardiovascular toxicities (including atrial fibrillation, ventricular arrhythmias, and hypertension) are the adverse events (AEs) commonly associated with BTKis. Initiation of therapy with venetoclax requires close monitoring because of the risk for tumor lysis syndrome associated with this agent, particularly in patients with a high disease burden. Development of newer target therapies is ongoing and the therapeutic landscape in CLL is expanding rapidly. Full article

(This article belongs to the Special Issue State of the Art Papers from 'The Society of Hematologic Oncology Italy – SOHO ITALY')

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10 pages, 5560 KiB

Open AccessEditor’s ChoiceCase Report

Fluid Overload-Associated Large B-Cell Lymphoma: A Case Report and Review of Literature

by Hisham F. Bahmad, Aaron S. Gomez, Arunima Deb, Fernando Martin Safdie and Vathany Sriganeshan

Hematol. Rep. 2023, 15(3), 411-420; https://doi.org/10.3390/hematolrep15030042 - 3 Jul 2023

Cited by 4 | Viewed by 3132

Abstract

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or [...] Read more.

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or pericardial) in the absence of an identifiable tumor mass. We present a case of an 82-year-old man with a history of atrial fibrillation and atrial flutter, status post-ablation, essential hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) type 2 who was referred to our hospital for shortness of breath due to recurrent pleural effusion. Right video-assisted thoracoscopy with right pleural biopsy was performed. Histopathological examination of the pleural biopsy revealed dense fibrous tissue, chronic inflammation, lymphoid aggregates, and granulation tissue, with no evidence of lymphoma. Cytology of the right pleural fluid revealed large lymphoid cells, which were positive for CD45, CD20, PAX-5, MUM-1, BCL2, BCL6, and MYC protein. They were negative for CD3, CD10, CD138, and HHV-8 by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was negative by in situ hybridization (ISH). Due to the absence of any evidence of lymphoma elsewhere, a diagnosis of fluid overload-associated large B-cell lymphoma (FO-LBCL) was made. We provide a synopsis of the main clinicopathological features of FO-LBCL and the two main differential diagnoses, primary effusion lymphoma (PEL) and diffuse large B-cell lymphoma (DLBCL). Full article

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6 pages, 221 KiB

Open AccessEditor’s ChoiceCase Report

Platelet Delta (δ)-Storage Pool Deficiency: A Case Series and Review of the Literature

by Amir F. Beirat, Sasmith R. Menakuru and Maitri Kalra

Hematol. Rep. 2023, 15(3), 405-410; https://doi.org/10.3390/hematolrep15030041 - 29 Jun 2023

Cited by 2 | Viewed by 2555

Abstract

Hereditary platelet delta (δ)-storage pool deficiency is a rare condition in which there are fewer dense granules in platelets disrupting primary hemostasis. It can cause a mild–moderate bleeding tendency with normal coagulation studies; hence, it is an underdiagnosed diagnostic challenge. The authors present [...] Read more.

Hereditary platelet delta (δ)-storage pool deficiency is a rare condition in which there are fewer dense granules in platelets disrupting primary hemostasis. It can cause a mild–moderate bleeding tendency with normal coagulation studies; hence, it is an underdiagnosed diagnostic challenge. The authors present three patients with hereditary platelet delta (δ)-storage pool deficiency who had heavy menstrual bleeding, excessive bleeding following surgery, mucocutaneous bleeding, and a bleeding score greater than or equal to 6. These cases reveal the susceptibility of underdiagnosing platelet disorders and the significance of utilizing a bleeding assessment tool to help guide further workup with transmission electron microscopy to visualize the fewer dense granules in platelets. Although bleeding is typically moderate, it can be severe in certain scenarios, like after mucosal surgeries, and can lead to death, highlighting the importance of the condition’s recognition and prophylactic treatment. Full article

7 pages, 422 KiB

Open AccessEditor’s ChoiceBrief Report

Risk Factors for Death or Cardiovascular Events after Acute Coronary Syndrome in Patients with Myeloproliferative Neoplasms

by Orly Leiva, Andrew Jenkins, Rachel P. Rosovsky, Rebecca K. Leaf, Katayoon Goodarzi and Gabriela Hobbs

Hematol. Rep. 2023, 15(2), 398-404; https://doi.org/10.3390/hematolrep15020040 - 7 Jun 2023

Cited by 6 | Viewed by 3693

Abstract

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of cardiovascular disease (CVD), including acute coronary syndrome (ACS). However, data on long-term outcomes of patients with MPN who have had ACS and risk factors for all-cause death or CV events post-ACS hospitalization are [...] Read more.

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of cardiovascular disease (CVD), including acute coronary syndrome (ACS). However, data on long-term outcomes of patients with MPN who have had ACS and risk factors for all-cause death or CV events post-ACS hospitalization are lacking. We conducted a single-center study of 41 consecutive patients with MPN with ACS hospitalization after MPN diagnosis. After a median follow-up of 80 months after ACS hospitalization, 31 (76%) experienced death or a CV event (myocardial infarction, ischemic stroke, or heart failure hospitalization). After multivariable Cox proportional hazards regression, index ACS within 12 months of MPN diagnosis (HR 3.84, 95% CI 1.44–10.19), WBC ≥ 20 K/µL (HR 9.10, 95% CI 2.71–30.52), JAK2 mutation (HR 3.71, 95% CI 1.22–11.22), and prior CVD (HR 2.60, 95% CI 1.12–6.08) were associated with increased death or CV events. Further studies are warranted to improve cardiovascular outcomes in this patient population. Full article

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12 pages, 923 KiB

Open AccessEditor’s ChoiceReview

Role of Therapeutic Anticoagulation in COVID-19: The Current Situation

by Mandeep Singh Rahi, Jay Parekh, Prachi Pednekar, Mayuri Mudgal, Vishal Jindal and Kulothungan Gunasekaran

Hematol. Rep. 2023, 15(2), 358-369; https://doi.org/10.3390/hematolrep15020037 - 5 Jun 2023

Cited by 5 | Viewed by 2961

Abstract

Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for [...] Read more.

Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19. Few randomized, controlled trials have examined the role of therapeutic anticoagulation in moderately to severely ill patients with COVID-19. Most of these patients had elevated D-dimers and low bleeding risks. Some trials used an innovative adaptive multiplatform with Bayesian analysis to answer this critical question promptly. All the trials were open-label and had several limitations. Most trials showed improvements in the meaningful clinical outcomes of organ-support-free days and reductions in thrombotic events, mainly in non-critically-ill COVID-19 patients. However, the mortality benefit needed to be more consistent. A recent meta-analysis confirmed the results. Multiple centers initially adopted intermediate-dose thromboprophylaxis, but the studies failed to show meaningful benefits. Given the new evidence, significant societies have suggested therapeutic anticoagulation in carefully selected patients who are moderately ill and do not require an intensive-care-unit level of care. There are multiple ongoing trials globally to further our understanding of therapeutic-dose thromboprophylaxis in hospitalized patients with COVID-19. In this review, we aim to summarize the current evidence regarding the use of anticoagulation in patients with COVID-19 infection. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Congenital and Acquired Haemorrhagic Disorders, Thromboembolic Disease and Platelet Disorders)

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11 pages, 277 KiB

Open AccessEditor’s ChoiceArticle

Etiology of Anemia and Risk Factors of Mortality among Hospitalized Patients: A Real-Life Retrospective Study in a Tertiary Center in Greece

by Petros Ioannou, Andria Papazachariou, Maria Tsafaridou, Ioannis E. Koutroubakis and Diamantis P. Kofteridis

Hematol. Rep. 2023, 15(2), 347-357; https://doi.org/10.3390/hematolrep15020036 - 2 Jun 2023

Cited by 1 | Viewed by 2961

Abstract

Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors [...] Read more.

Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors of this condition should be performed. The aim of the present study was to examine the causes of anemia in hospitalized patients in a tertiary hospital in Greece and identify risk factors related to higher mortality. In total, 846 adult patients with a diagnosis of anemia were admitted during the study period. The median age was 81 years, and 44.8% were male. The majority of patients had microcytic anemia, with the median mean corpuscular volume (MCV) being 76.3 fL and the median hemoglobin being 7.1 g/dL. Antiplatelets were used by 28.6% of patients, while 28.4% were using anticoagulants at the time of diagnosis. At least one unit of packed red blood cells (PRBCs) was transfused in 84.6% of patients, and a median of two PRBCs was used per patient. A gastroscopy was performed in 55%, and a colonoscopy was performed in 39.8% of patients in the present cohort. Anemia was considered to be multifactorial in almost half the cases, while the most commonly identified cause was iron deficiency anemia, more commonly with positive endoscopic findings. Mortality was relatively low, at 4.1%. Multivariate logistic regression analysis identified higher B12 levels and longer duration of hospital stay to be independently positively associated with mortality. Full article

16 pages, 1443 KiB

Open AccessEditor’s ChoiceReview

Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment

by Shinichiro Takahashi

Hematol. Rep. 2023, 15(2), 331-346; https://doi.org/10.3390/hematolrep15020035 - 24 May 2023

Cited by 9 | Viewed by 3142

Abstract

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators [...] Read more.

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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7 pages, 661 KiB

Open AccessEditor’s ChoiceCase Report

A Report of a Symptomatic Progressive Myeloma during Pregnancy and Postpartum Period from Asymptomatic State

by Gehad Elgabry, Lydia Spencer, Hisam Siddiqi, Soumya Ojha and Farooq Wandroo

Hematol. Rep. 2023, 15(2), 305-311; https://doi.org/10.3390/hematolrep15020031 - 5 May 2023

Cited by 2 | Viewed by 2576

Abstract

Multiple myeloma is a plasma cell malignancy that is most commonly observed in males in the sixth and seventh decade of life. The clinical scenario of multiple myeloma with concurrent pregnancy is considered to be very rare. We detail here the case [...] Read more.

Multiple myeloma is a plasma cell malignancy that is most commonly observed in males in the sixth and seventh decade of life. The clinical scenario of multiple myeloma with concurrent pregnancy is considered to be very rare. We detail here the case of a young female with known IgG kappa multiple myeloma who was found to have a steady elevation of her IgG kappa paraprotein during pregnancy and symptomatic progression in the postpartum period. She delivered a healthy baby at 40 weeks gestation. We present a review of all reported cases of known multiple myeloma progressing during pregnancy and in the postpartum period, the treatments given, and their outcomes. The report also provides suggestions for diagnosis and management of myeloma during pregnancy in order to have an outcome of successful uncomplicated pregnancy with healthy offspring. Full article

(This article belongs to the Special Issue Opportunities and Challenges in Multiple Myeloma Treatment and Management)

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8 pages, 2063 KiB

Open AccessEditor’s ChoiceCase Report

Testosterone Usage Leading to Pulmonary Embolisms and Deep Vein Thrombosis: A Case Report and Review of the Literature

by Sasmith R. Menakuru, Mona Atta, Vijaypal S. Dhillon and Ahmed Salih

Hematol. Rep. 2023, 15(2), 290-297; https://doi.org/10.3390/hematolrep15020029 - 26 Apr 2023

Cited by 5 | Viewed by 4426

Abstract

Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented [...] Read more.

Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented to the hospital after the usage of testosterone for one month, leading to the development of multiple pulmonary emboli and deep vein thrombosis. The authors hope to elucidate the relationship between testosterone usage and thrombosis formation. Full article

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7 pages, 577 KiB

Open AccessEditor’s ChoiceCase Report

A Case of Vancomycin-Induced Severe Immune Thrombocytopenia

by Shivani Shah, Ryan Sweeney, Maitreyee Rai and Deep Shah

Hematol. Rep. 2023, 15(2), 283-289; https://doi.org/10.3390/hematolrep15020028 - 24 Apr 2023

Cited by 3 | Viewed by 3852

Abstract

A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it [...] Read more.

A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it rapidly decreased to 11 k/mcl on day 16 when the INR was 1.3 and aPTT was 32 s, and he continued to have a stable anemia throughout admission. There was no response in platelet count post-transfusion of four units of platelets. Hematology initially evaluated the patient for disseminated intravascular coagulation, heparin-induced thrombocytopenia (anti-PF4 antibody was 0.19), and thrombotic thrombocytopenic purpura (PLASMIC score of 4). Vancomycin was administered on days 1–7 for broad spectrum antimicrobial coverage and day 10, again, for concerns of sepsis. Given the temporal association of thrombocytopenia and vancomycin administration, a diagnosis of vancomycin-induced immune thrombocytopenia was established. Vancomycin was discontinued, and 2 doses of 1000 mg/kg of intravenous immunoglobulin 24 h apart were administered with the subsequent resolution of thrombocytopenia. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Congenital and Acquired Haemorrhagic Disorders, Thromboembolic Disease and Platelet Disorders)

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17 pages, 1550 KiB

Open AccessEditor’s ChoiceArticle

Changes in Hematologic Lab Measures Observed in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors, Ravulizumab and Eculizumab: Real-World Evidence from a US Based EMR Network

by Jesse Fishman, Seth Kuranz, Michael M. Yeh, Kaylen Brzozowski and Herman Chen

Hematol. Rep. 2023, 15(2), 266-282; https://doi.org/10.3390/hematolrep15020027 - 21 Apr 2023

Cited by 8 | Viewed by 3888

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. [...] Read more.

Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. Data were extracted from TriNetX Dataworks Network and included patients with a PNH diagnosis between 1 January 2010, and 20 August 2021. Patients were stratified into three cohorts based on their C5i usage: eculizumab, ravulizumab (prior eculizumab), and ravulizumab (eculizumab naïve). Hematological markers (hemoglobin [Hb], lactate dehydrogenase [LDH], and absolute reticulocyte count [ARC]) and relevant clinical events (e.g., breakthrough hemolysis [BTH], complement-amplifying conditions [CAC], thrombosis, infection, and all-cause mortality) were captured any time within 12 months post-index treatment. Of the 143 (eculizumab), 43 (ravulizumab, prior eculizumab), and 33 (ravulizumab, eculizumab naïve) patients, mean age across cohorts was 42–51 years, 55–61% were female, 63–73% were White, and 33–40% had aplastic anemia. Among all cohorts 12 months post-C5i treatment, 50–82% remained anemic, 8–32% required ≥1 transfusion, and 13–59% had BTH, of which 33%-54% had CACs. Additionally, thrombosis was seen in 7–15% of patients, infection in 20–25%, and mortality in 1–7%. These findings suggest many C5i-treated patients experience suboptimal disease control. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Congenital and Acquired Haemorrhagic Disorders, Thromboembolic Disease and Platelet Disorders)

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10 pages, 273 KiB

Open AccessEditor’s ChoiceArticle

Utilization of Genomic Tumor Profiling in Pediatric Liquid Tumors: A Clinical Series

by Ishna Sharma, Min Ji Son, Shoaleh Motamedi, Alice Hoeft, Christa Teller, Tyler Hamby and Anish Ray

Hematol. Rep. 2023, 15(2), 256-265; https://doi.org/10.3390/hematolrep15020026 - 19 Apr 2023

Cited by 2 | Viewed by 1835

Abstract

Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric [...] Read more.

Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric liquid tumors. There is also no consensus on when profiling should be performed and its use in guiding therapies. We describe a single institution’s experience in integrating profiling for liquid tumors. Pediatric patients diagnosed with leukemia or lymphoma and who underwent tumor profiling were retrospectively reviewed. Ten (83.3%) patients had relapsed disease prior to tumor profiling. Eleven (91.7%) patients had targetable alterations identified on profiling, and three (25%) received targeted therapy based on these variants. Of the three patients that received targeted therapy, two (66.7%) were living, and one (33.3%) decreased. For a portion of our relapsing and/or treatment-refractory patients, genetic profiling was feasible and useful in tailoring therapy to obtain stable or remission states. Practitioners may hesitate to deviate from the ‘standard of therapy’, resulting in the underutilization of profiling results. Prospective studies should identify actionable genetic variants found more frequently in pediatric liquid tumors and explore the benefits of proactive tumor profiling prior to the first relapse. Full article

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