Hematology Reports

20 pages, 1484 KB

Open AccessReview

Pernicious Anemia: Basic Pathophysiology and Diagnostic Challenges in Neuropsychiatric Patients

by Yin Mon Myat, Kyaw Zin Thein and Thein Hlaing Oo

Hematol. Rep. 2026, 18(4), 47; https://doi.org/10.3390/hematolrep18040047 - 1 Jul 2026

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying [...] Read more.

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage. Full article

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

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11 pages, 249 KB

Open AccessReview

A Scoring System for the Assessment of Quality of Care in the Management of Transfusion Dependent Thalassemia

by Michael Angastiniotis, Lily Cannon and Androulla Eleftheriou

Hematol. Rep. 2026, 18(4), 46; https://doi.org/10.3390/hematolrep18040046 - 1 Jul 2026

Abstract

Objective: To identify criteria which can be used locally to assess the quality of care for thalassaemia patients, leading to quality improvement measures. In low-resource settings, there is often minimal support for services, and the investigations used in patient monitoring are very [...] Read more.

Objective: To identify criteria which can be used locally to assess the quality of care for thalassaemia patients, leading to quality improvement measures. In low-resource settings, there is often minimal support for services, and the investigations used in patient monitoring are very basic. In order to select standards which can serve quality assessment, consideration is given to what is available in most centres. Importance is given to the need for the local service provider to self-assess the quality of care according to evidence-based minimal standards. Methods: A search in the recent literature was performed to identify measures of quality care in thalassaemia, selecting those which can be used in resource-poor settings. They are then compared to the standards listed in internationally accepted guidelines. Results: Twelve criteria were selected based on the routine information recorded by most centres. These include the following: clinical criteria: mean age (excluding paediatric clinics), pre-transfusion Hb < 9 g/dL, serum ferritin, MRI availability, heart iron (where available) >20 ms, LIC (where available) <3 mg/kg dw, LIC > 15 mg/kg dw, combination chelation within the last year, and BMI < 18.5 kg/m². Social criteria (for adults): completed tertiary education, married/cohabiting, and employed full or part-time. Each is assigned a score with a total range from 0 to 10. Conclusions: Annual scoring according to achievements allows service providers to compare with previous years and conclude which of the basic services need to be further upgraded to achieve quality improvement. Scoring also allows for comparison with standards published in international guidelines. The clear aim is to aim for higher scores each year, indicating better patient outcomes. Full article

11 pages, 2343 KB

Open AccessArticle

The Use of Point-of-Care Hemoglobin Measurements in an Elderly Population with Hematological Disorders and Anemia

by Ittai Appel, Liat Dizengoff, Nili Stein, Regina Draliuk, Alla Kravits, Shoshan Perek, Amir Warwar, Ibrahim Zoubi, Marwa Naamneh, Adi Kibari, Mouna Ballan-Haj, Olga Valkovsky, Elena Mishchenko and Meir Preis

Hematol. Rep. 2026, 18(4), 45; https://doi.org/10.3390/hematolrep18040045 - 30 Jun 2026

Abstract

Background: Patients with severe chronic anemia often require frequent blood transfusions. Many are elderly with comorbidities and limited mobility, making regular hospital visits burdensome. In some cases, patients may receive transfusions despite hemoglobin levels being above the clinical threshold due to logistical challenges, [...] Read more.

Background: Patients with severe chronic anemia often require frequent blood transfusions. Many are elderly with comorbidities and limited mobility, making regular hospital visits burdensome. In some cases, patients may receive transfusions despite hemoglobin levels being above the clinical threshold due to logistical challenges, leading to unnecessary exposure to risks, inefficient use of blood units, and resource strain. This study aims to evaluate the use of point-of-care (POC) hemoglobin measurements under controlled outpatient clinic conditions, as an initial step toward potential future home-based monitoring by the patients or their caregivers, with the goal of optimizing transfusion timing, aiming to reduce unnecessary hospital visits while maintaining patient safety. Methods: A total of 127 patients from a hemato-oncology outpatient clinic at Carmel Medical Center were evaluated using a nurse-operated POC device to sample capillary blood, with 236 paired measurements concurrently analyzed via venous blood in the laboratory. Demographic and clinical data were assessed to evaluate factors associated with agreement between POC and laboratory measurements. Statistical analysis included Bland–Altman plots and Pearson correlation coefficients. Results: The POC device showed a moderate correlation with laboratory results (r = 0.73, p < 0.001), with a mean difference of 1.20 g/dL (SD = 1.94 g/dL) but wide limits of agreement (−3.20 to 5.50 g/dL). No significant differences were observed across demographic or clinical subgroups. Notably, all 156 paired measurements with POC-measured hemoglobin >7 g/dL were confirmed by laboratory testing. Conclusions: Although POC hemoglobin devices are not suitable as standalone tools for routine monitoring of chronic anemia, the high negative predictive value observed at the 7 g/dL threshold suggests that they may be useful for ruling out severe anemia. If validated in larger multicenter and home-use studies, POC Hb devices might contribute to reducing unnecessary hospital visits and transfusions. Full article

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14 pages, 262 KB

Open AccessReview

Role of Autologous Haematopoietic Transplantation in Leukaemias: When to Consider It in 2026

by Miklós Udvardy, Lajos Gergely, Róbert Szász, Gyula Reményi, László Imre Pinczés and Árpád Illés

Hematol. Rep. 2026, 18(4), 44; https://doi.org/10.3390/hematolrep18040044 - 29 Jun 2026

Abstract

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of [...] Read more.

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients. Full article

14 pages, 2460 KB

Open AccessSystematic Review

Efficacy and Safety of Lisocabtagene Maraleucel in Relapsed or Refractory Large B-Cell Lymphoma: A Product-Specific Systematic Review and Meta-Analysis of Clinical Trials and Real-World Studies

by Jerry Qi, Daniel Park, Nidhi Kejriwal, Austin Yang, Kareem Latif, Sarkis Dagley and Mojtaba Akhtari

Hematol. Rep. 2026, 18(4), 43; https://doi.org/10.3390/hematolrep18040043 - 23 Jun 2026

Abstract

Background/Objectives: Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. Methods: We conducted a [...] Read more.

Background/Objectives: Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. Methods: We conducted a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating liso-cel monotherapy in R/R LBCL. The primary endpoint was the overall response rate (ORR). Secondary endpoints included complete response (CR), incidence of grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), overall mortality rate (OMR), disease progression-related mortality, and adverse event-related mortality. Pooled proportions were estimated using random-effects models. Results: Eleven studies including 1206 patients were analyzed, comprising five clinical trials and six real-world retrospective cohorts. The pooled ORR was 78%, and the pooled CR rate was 60%. The pooled OMR was 38%, with a disease progression-related mortality of 28% and an adverse event-related mortality of 4%. Severe (grade ≥ 3) CRS and ICANS occurred in 2% and 8%, respectively. Severe (grade ≥ 3) hematologic toxicities were frequent, particularly neutropenia, thrombocytopenia, and anemia. Conclusions: Liso-cel monotherapy demonstrated high pooled response rates and low pooled incidences of severe CRS and ICANS across clinical trials and real-world settings in R/R LBCL. Severe ICANS, although uncommon, remains clinically meaningful, and severe hematologic toxicities were frequent and warrant careful monitoring and supportive care. These findings provide product-specific benchmarks for liso-cel in R/R LBCL. Full article

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16 pages, 1519 KB

Open AccessReview

The Global Gap in the Hemophilia Paradigm Shift: Disparities in Research, Care, and Musculoskeletal Health

by Felipe Querol-Giner, Magdalena Querol-Giner, Ana Chimeno-Hernández, Pilar Alberola-Zorrilla, Sofía Pérez-Alenda, Santiago Bonanad and Felipe Querol-Fuentes

Hematol. Rep. 2026, 18(3), 42; https://doi.org/10.3390/hematolrep18030042 - 22 Jun 2026

Abstract

Background: Hemophilia care has undergone a major therapeutic transformation with the introduction of extended half-life products, non-replacement therapies, and gene therapy. However, the benefits of these advances are not equally distributed worldwide, and their impact on long-term musculoskeletal outcomes remains uncertain. Objective: To [...] Read more.

Background: Hemophilia care has undergone a major therapeutic transformation with the introduction of extended half-life products, non-replacement therapies, and gene therapy. However, the benefits of these advances are not equally distributed worldwide, and their impact on long-term musculoskeletal outcomes remains uncertain. Objective: To analyze global disparities in hemophilia care and research production in the context of recent therapeutic advances, with particular attention to musculoskeletal management, physiotherapy, and scalable strategies for resource-limited settings. Methods: A narrative review with a structured literature search was conducted. Two conceptual blocks were explored: global disparities and access to care in hemophilia, and recent therapeutic advances, including non-replacement therapies, extended half-life products, and gene therapy. Retrieved records were screened using Rayyan, and a structured workflow diagram was used to summarize the literature identification and selection process. A descriptive analysis was also performed to identify representative authors, institutions, and geographic patterns in hemophilia research. Results: The evidence shows substantial global disparities in diagnosis, access to treatment, healthcare infrastructure, and research production. Scientific output remains concentrated in high-income countries, while low- and middle-income regions are underrepresented. Advanced therapies consistently reduce bleeding rates and treatment burden, but concerns remain regarding access, affordability, durability, breakthrough bleeding, and long-term structural joint outcomes. Musculoskeletal complications, including subclinical bleeding and hemophilic arthropathy, remain clinically relevant despite improved hematologic control. Conclusions: The current paradigm shift in hemophilia care is not uniformly experienced worldwide. Addressing global disparities requires not only expanding access to advanced therapies, but also strengthening research capacity, implementing multidisciplinary care models, and integrating scalable interventions such as physiotherapy, patient education, and simplified diagnostic tools. Accessible musculoskeletal assessment strategies may help improve early detection, functional outcomes, and equity of care in resource-limited settings. Full article

(This article belongs to the Special Issue Hemophilia: The Paradigm Shift and the Unresolved Challenges)

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10 pages, 783 KB

Open AccessArticle

Digital Symptom Reporting for Treatment Readiness Before Daratumumab: A Blinded Prospective Study in Multiple Myeloma

by Tine Rosenberg, Jannie Kirkegaard, Michael Tveden Gundesen, Anne Mette Ølholm, Karin Brochstedt Dieperink and Thomas Lund

Hematol. Rep. 2026, 18(3), 41; https://doi.org/10.3390/hematolrep18030041 - 15 Jun 2026

Abstract

Objectives: For patients with multiple myeloma (MM), an increasing proportion of treatment is now delivered at home. While this shift offers convenience and supports continuity of care, it also demands new ways to ensure patient safety outside the hospital. Although patients receiving home-based [...] Read more.

Objectives: For patients with multiple myeloma (MM), an increasing proportion of treatment is now delivered at home. While this shift offers convenience and supports continuity of care, it also demands new ways to ensure patient safety outside the hospital. Although patients receiving home-based treatment are generally clinically stable, each administration still requires a pre-treatment safety assessment, traditionally performed by telephone. We aimed to evaluate whether digital patient-reported outcomes (PROs) could replace these calls to determine treatment readiness. Methods: This feasibility study included 30 patients (median age 76 years, 60% male). Prior to each scheduled treatment, patients completed a digital symptom questionnaire. An algorithm stratified patients according to treatment readiness. In total, 233 questionnaires were distributed and 179 completed (completion rate 77%). Healthcare professionals were blinded to PRO data during the study, and PRO-based assessments were compared with standard nurse-led telephone evaluations after study completion. Results: Digital PRO data reliably identified patients ready for treatment. The algorithm achieved a positive predictive value of 100%, indicating concordance between PRO-based readiness classification and clinical decisions. The negative predictive value was 19%, reflecting that most patients reporting symptoms were ultimately eligible for treatment. Overall, nearly 80% of routine pre-treatment telephone calls could safely be omitted without compromising patient safety. Conclusions: This study suggests that digital PRO-based symptom reporting may support a reduction in routine pre-treatment telephone assessments for selected patients with MM receiving daratumumab. The approach showed potential for streamlining clinical workflows while maintaining patient safety, although confirmatory studies are needed before implementation. Full article

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Graphical abstract

25 pages, 693 KB

Open AccessReview

Quality of Life in CAR-T Cell Therapy

by Caterina Alati, Martina Pitea, Gaetana Porto, Giorgia Policastro, Erica Bilardi, Giovanna Utano, Laura Giordano, Annalisa Sgarlata, Ilaria Maria Delfino, Aurora Idato, Giulia Santoro, Filippo Antonio Canale, Virginia Naso and Massimo Martino

Hematol. Rep. 2026, 18(3), 40; https://doi.org/10.3390/hematolrep18030040 - 10 Jun 2026

Abstract

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed or refractory hematologic malignancies, achieving high response rates in B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. While the efficacy of CAR-T therapy is well established, [...] Read more.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed or refractory hematologic malignancies, achieving high response rates in B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. While the efficacy of CAR-T therapy is well established, quality of life (QoL) metrics have become increasingly important for guiding treatment decisions, patient counseling, and survivorship planning. Objectives: Most patients undergoing CAR-T therapy recover their initial QoL within 3 months, an improvement not typically seen with other treatment options. A comprehensive understanding of QoL is essential for delivering patient-centered care in the evolving CAR-T landscape. Conclusions: This review synthesizes current evidence on QoL outcomes in CAR-T recipients, including acute effects, recovery trajectories, comparisons with conventional therapies, and strategies to optimize QoL. Full article

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11 pages, 232 KB

Open AccessArticle

Eltrombopag for Chemotherapy-Induced Thrombocytopenia: A Multicenter Retrospective Real-World Study

by Mehmet Baysal, Fatos Dilan Köseoğlu, Sevil Sadri, Ünal Ataş, Ufuk Demirci, Rafiye Çiftçiler, Seval Akpınar and Elif Gülsüm Ümit

Hematol. Rep. 2026, 18(3), 39; https://doi.org/10.3390/hematolrep18030039 - 10 Jun 2026

Abstract

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a common dose-limiting toxicity that disrupts on-time, full-dose chemotherapy, yet no pharmacologic therapy is formally approved. Growing evidence from randomized and late-phase studies with thrombopoietin receptor agonists (TPO-RAs) has renewed interest in targeted supportive care. We evaluated the [...] Read more.

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a common dose-limiting toxicity that disrupts on-time, full-dose chemotherapy, yet no pharmacologic therapy is formally approved. Growing evidence from randomized and late-phase studies with thrombopoietin receptor agonists (TPO-RAs) has renewed interest in targeted supportive care. We evaluated the effectiveness and safety of eltrombopag for CIT in routine clinical practice. Methods: We conducted a small, retrospective, single-arm multicenter cohort study of 31 adults with solid tumors (74.2% stage IV). Given the descriptive, hypothesis-generating nature of this study, no causal inference regarding efficacy can be drawn. Platelet counts and chemotherapy continuity were tracked from baseline through week 12 after eltrombopag initiation. Bleeding, thrombosis, and laboratory safety signals were recorded. Results: The median platelet count increased from 33 × 10⁹/L at baseline to 71 × 10⁹/L at week 1 and 99.5 × 10⁹/L by week 12. Overall, 18/31 patients (58.1%) resumed chemotherapy within 3 weeks, and 15/31 (48.4%) completed planned regimens by week 6. Adverse events were limited to mild, transient elevations in transaminases (n = 3); no major bleeding or thrombotic events occurred. Conclusions: In this real-world multicenter cohort, eltrombopag was associated with rapid platelet recovery and improved chemotherapy deliverability with an acceptable safety profile. The retrospective, single-arm design and the hypothesis-generating nature of these findings preclude definitive conclusions regarding causal efficacy. These observational data highlight the need for prospective controlled trials to characterize the clinical role, optimal dosing, and long-term safety of oral TPO-RAs in CIT. Full article

6 pages, 306 KB

Open AccessArticle

Establishing Reference Intervals for White Blood Cell and Absolute Neutrophil Counts in Duffy Null Individuals

by Mohammad Barouqa, Muhammad Areeb Ashfaq, Katrina J. Jiang, Huseyin Kilic, Nestor Dela Cruz, Aariez Khalid and Marianne E. Yassa

Hematol. Rep. 2026, 18(3), 38; https://doi.org/10.3390/hematolrep18030038 - 8 Jun 2026

Abstract

Background/Objectives: The Duffy (Fy) blood group system, encoded by the ACKR1 gene, plays a key role in transfusion medicine and host susceptibility to malarial infections such as Plasmodium vivax. The Duffy-null phenotype [Fy(a−b−)] is associated with lower baseline white blood cell (WBC) [...] Read more.

Background/Objectives: The Duffy (Fy) blood group system, encoded by the ACKR1 gene, plays a key role in transfusion medicine and host susceptibility to malarial infections such as Plasmodium vivax. The Duffy-null phenotype [Fy(a−b−)] is associated with lower baseline white blood cell (WBC) and absolute neutrophil count (ANC) values despite a benign clinical course. This study aimed to establish specific reference intervals for WBC and ANC in Duffy-null individuals to improve diagnostic accuracy and reduce unnecessary clinical interventions. Methods: We conducted a retrospective analysis of 1695 adult patients who underwent complete blood count testing and red blood cell phenotyping between 1 January 2020 and 1 January 2026. Among these, 122 healthy individuals with confirmed Fy(a−b−) phenotype met inclusion criteria. Reference intervals were established using 95% reference interval nonparametric methods in accordance with Clinical Laboratory Standards Institute (CLSI) guidelines. Results: The median WBC and ANC values in the Duffy-null cohort were significantly lower than institutional reference medians (3.24 vs. 6.65 × 10³/µL and 1.45 vs. 4.45 × 10³/µL, respectively; p < 0.01). The derived 95% reference intervals (WBC: 2.43–7.05 × 10³/µL; ANC: 1.01–4.34 × 10³/µL) fell below conventional thresholds, with the lower ANC bound below the standard neutropenia cutoff. Conclusions: These findings support the need for Duffy-null-specific hematologic reference ranges. Adoption of such intervals may reduce misclassification, avoid unnecessary diagnostic procedures, and promote personalized clinical care. Full article

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14 pages, 1052 KB

Open AccessReview

Perioperative Anemia, Transfusion Practices, and Patient Blood Management: Lessons from the COVID-19 Pandemic

by Alin Ionescu, Alexandra Mihăilescu, Raluca Dumache, Alexandru Capcelea, Alexander Dean Turceanu, Nicolae Albulescu and Mihai Alexandru Săndesc

Hematol. Rep. 2026, 18(3), 37; https://doi.org/10.3390/hematolrep18030037 - 30 May 2026

Abstract

The COVID-19 pandemic exposed vulnerabilities in global blood supply systems and accelerated the adoption of patient blood management (PBM) strategies aimed at optimizing transfusion practices in surgical care. Perioperative anemia is a key contributor to adverse outcomes and is frequently treated with allogeneic [...] Read more.

The COVID-19 pandemic exposed vulnerabilities in global blood supply systems and accelerated the adoption of patient blood management (PBM) strategies aimed at optimizing transfusion practices in surgical care. Perioperative anemia is a key contributor to adverse outcomes and is frequently treated with allogeneic blood transfusion (ABT), which carries infectious and immunologic risks. Iron deficiency remains the most common and potentially correctable cause of perioperative anemia. This narrative review examines various approaches to perioperative anemia, strategies to minimize reliance on ABT, and alternatives within the PBM paradigm. Evidence supports the use of iron therapy, erythropoiesis-stimulating agents, antifibrinolytic strategies, and blood conservation techniques to reduce transfusion requirements and improve clinical outcomes. Lessons from the COVID-19 pandemic highlight PBM as a framework to enhance transfusion safety and sustainability. Broader implementation of PBM may improve patient outcomes, reduce unnecessary transfusions, and preserve scarce blood resources. Full article

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

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8 pages, 589 KB

Open AccessBrief Report

Bortezomib in Patients Who Fail BTKi in Waldenström Macroglobulinaemia

by Jahanzaib Khwaja, Nicole Japzon, Simona Gatto, Jindriska Lindsay, Charalampia Kyriakou and Shirley D’Sa

Hematol. Rep. 2026, 18(3), 36; https://doi.org/10.3390/hematolrep18030036 - 30 May 2026

Abstract

Background: Treatment options after Bruton’s tyrosine kinase inhibitors (BTKi) failure in Waldenstrom macroglobulinaemia are limited. Methods: We retrospectively analysed the use of bortezomib after BTKi failure in 17 patients who were heavily pre-treated and chemotherapy-exposed at our centre between 2018 and 2025. Results: [...] Read more.

Background: Treatment options after Bruton’s tyrosine kinase inhibitors (BTKi) failure in Waldenstrom macroglobulinaemia are limited. Methods: We retrospectively analysed the use of bortezomib after BTKi failure in 17 patients who were heavily pre-treated and chemotherapy-exposed at our centre between 2018 and 2025. Results: Reasons for BTKi failure were disease progression (59%) and intolerance (41%). At bortezomib initiation, the median age was 73 years and two patients experienced grade 1–2 neuropathy. The best overall response rate (ORR) was 88%. At a median follow up of 39 months (interquartile range 35–78), median treatment-free survival and overall survival were 18 (95% confidence interval [CI] 13–22) and 22 (95% CI 17–45) months, respectively. Conclusion: Bortezomib may be efficacious in patients who experience BTKi failure. Full article

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11 pages, 3308 KB

Open AccessReview

Delayed Rewarming Thrombocytopenia (DRT): A Temperature-Dependent Platelet Aggregation Disorder

by Ian Joseph Cohen

Hematol. Rep. 2026, 18(3), 35; https://doi.org/10.3390/hematolrep18030035 - 27 May 2026

Abstract

Below 32 °C, the second irreversible stage of platelet aggregation is absent, causing augmentation of the first reversible stage of platelet aggregation and adhesion. During rewarming, de-aggregation occurs; however, in the presence of adequate ADP (adenosine diphosphate), the second stage of aggregation occurs, [...] Read more.

Below 32 °C, the second irreversible stage of platelet aggregation is absent, causing augmentation of the first reversible stage of platelet aggregation and adhesion. During rewarming, de-aggregation occurs; however, in the presence of adequate ADP (adenosine diphosphate), the second stage of aggregation occurs, leading to delayed rewarming thrombocytopenia (DRT). Erythrocytes leak ADP in sufficient amounts by 24 h to cause DRT. This is prevented by rewarming within 24 h. Heparin before hypothermia prevents platelet adhesion, as does alcohol, which also blocks the second phase of aggregation. Aspirin blocks the second phase of aggregation, and platelet infusions, stored without erythrocytes, are an effective therapy. DRT explains rewarming deaths in NCI (neonatal cold injury). Full article

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15 pages, 6670 KB

Open AccessArticle

Sociodemographic, Clinical, and Therapeutic Characterization of Multiple Myeloma Patients (CharisMMa Study) with Symptomatic Relapse and/or Refractory Disease: An Observational, Multicenter Study in Portugal

by Rui Bergantim, José Guilherme Freitas, Cristina Gonçalves, Helena Martins, Herlander Marques, Henrique Coelho, Patrícia Seabra, Adriana Roque, Márcio Tavares, Pedro Pinto, Ana Rita Francisco, Joana Tato and Catarina Geraldes

Hematol. Rep. 2026, 18(3), 34; https://doi.org/10.3390/hematolrep18030034 - 19 May 2026

Abstract

Objectives: Real-world information on relapsed and/or refractory multiple myeloma (rrMM) clinical management in Portugal is scarce. The CharisMMa Portugal study aimed to characterize rrMM patients through socio-demographic and clinical parameters and describe treatment patterns. Methods: This was an observational, cross-sectional, multicenter study with [...] Read more.

Objectives: Real-world information on relapsed and/or refractory multiple myeloma (rrMM) clinical management in Portugal is scarce. The CharisMMa Portugal study aimed to characterize rrMM patients through socio-demographic and clinical parameters and describe treatment patterns. Methods: This was an observational, cross-sectional, multicenter study with 62 rrMM patients routinely treated at seven hospitals in Portugal. Data were collected from medical records during clinical appointments (2020–2022) after written informed consent was obtained (ClincialTrials.gov ID-NCT04135963). Patients who were diagnosed with a symptomatic MM episode in the 6 months prior to study initiation and who received treatment before their last relapse episode were enrolled. Results: Most patients were male (54.8%) and living with relatives (90.3%), and almost 50% were independent. Roughly 70% of patients were classified as Revised MM International Staging System (R-ISS) Stage II at diagnosis, with a mean age of 65.76 (±9.24) years old. Most common SliM-CRAB (SLIM: sixty percent or more clonal plasma cells in the bone marrow (S), light chain ratio ≥100 (Li), and MRI-detected focal lesions (M); CRAB: hypercalcemia (C), renal insufficiency (R), anemia (A), and bone lesions (B)) signs were bone lesions (59%), and 62.9% of the patients had at least one comorbidity. At study initiation, 70.5% of patients were on second-line treatment, with monoclonal antibodies and proteasome inhibitors (PIs) + immunomodulators (IMiDs) as leading agents. Triplet regimens were the most common across all lines, while oral and oral + subcutaneous were the most prevalent routes of administration. Conclusions: Triple treatment combinations are common in rrMM management, with PIs and IMiDs frequently used, especially in first-line settings. The use of oral formulation is substantial, suggesting a step toward more patient-centric options. This characterization underscores the complexity of rrMM management and should inform stakeholders of strategies to standardize patient care across reference centers in Portugal. Full article

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12 pages, 755 KB

Open AccessReview

Novel Approaches to the Management of Myelodysplastic Syndromes: The Roles of Artificial Intelligence and Oxidative Stress Biomarkers

by Ioannis Tsamesidis, Georgios Drillis, Sotirios Varlamis, Niki Smaragdaki, Philippos Klonizakis, Maria Dimou, Konstantinos Liapis, Georgios Vrahiolias, Eleni Andreadou, Stella Mitka, Maria Chatzidimitriou, Ioannis Kotsianidis, Petros Skepastianos, Anastasios G. Kriebardis and Ilias Pessach

Hematol. Rep. 2026, 18(3), 33; https://doi.org/10.3390/hematolrep18030033 - 15 May 2026

Abstract

Objectives: Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, genomic instability, and a high risk of progression to acute myeloid leukemia. Oxidative stress (OS) has emerged as a central factor in MDS pathophysiology, contributing to [...] Read more.

Objectives: Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, genomic instability, and a high risk of progression to acute myeloid leukemia. Oxidative stress (OS) has emerged as a central factor in MDS pathophysiology, contributing to DNA damage, altered cellular signaling, and disease progression. Recent advances in artificial intelligence (AI) and machine learning (ML) offer a transformative approach for integrating multidimensional datasets including oxidative stress markers, hematologic parameters, and molecular profiles to enhance diagnosis, prognostication, and therapeutic monitoring in MDS. Methods: A comprehensive literature search was conducted in PubMed and Scopus, using the keywords “OS biomarkers,” “AI,” and “MDS’’. Results: Modified redox biomarkers can be correlated with oxidative imbalance and disease progression. ML models such as neural networks, decision trees, and support vector machines effectively capture complex relationships among redox biomarkers, enhancing risk stratification and prediction of treatment response. AI-driven proteomic analyses further revealed OS-related protein signatures linked to MDS pathophysiology. Overall, AI and ML enable the transformation of multidimensional OS data into clinically actionable tools for personalized management in MDS. Conclusions: Integrating biomarker research with AI-based analytics holds promise for advancing personalized diagnostics, prognostication, and therapeutic strategies in MDS, paving the way toward precision medicine. Full article

(This article belongs to the Special Issue Next-Generation Hematology: Artificial Intelligence and Biomarker-Driven Innovations in Diagnosis and Therapy)

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9 pages, 4369 KB

Open AccessCase Report

Leukemic Non-Nodal Mantle Cell Lymphoma Presenting with Traumatic Splenic Rupture

by Moinul Haque, Razie Amraei and Krasimira A. Rozenova

Hematol. Rep. 2026, 18(3), 32; https://doi.org/10.3390/hematolrep18030032 - 13 May 2026

Abstract

Background: Leukemic non-nodal variant mantle cell lymphoma (nnMCL) is an uncommon subtype of mantle cell lymphoma that lacks lymphadenopathy and generally follows an indolent clinical course. Adverse genetic alterations such as TP53 inactivation and del(13q) may have prognostic significance. Clinical findings such as [...] Read more.

Background: Leukemic non-nodal variant mantle cell lymphoma (nnMCL) is an uncommon subtype of mantle cell lymphoma that lacks lymphadenopathy and generally follows an indolent clinical course. Adverse genetic alterations such as TP53 inactivation and del(13q) may have prognostic significance. Clinical findings such as splenomegaly may serve as a clue to the diagnosis and should prompt further evaluation. Case Presentation: We describe a 91-year-old woman who presented with a one-month history of anemia (hemoglobin 12.3 g/dL), mild thrombocytopenia (platelets 136 × 10⁹/L), isolated splenomegaly and no palpable lymphadenopathy. Despite a normal total white blood cell count, intermittent relative lymphocytosis with atypical lymphocytes (4%) and smudge cells was detected on the complete blood count. Peripheral blood flow cytometry demonstrated a monoclonal kappa-restricted B-cell population negative for CD5 and CD10, comprising approximately 20% of lymphocytes. Conventional karyotyping and fluorescent in situ hybridization (FISH) analysis identified del(13q), del(17p)/TP53, and IGH-CCND1 rearrangement in 8–19.5% of peripheral blood leukocytes. A month after the initial assessment, the patient presented following a fall. CT imaging of the abdomen revealed marked splenomegaly, a large subcapsular/perisplenic hematoma, and moderate-to-large hemoperitoneum. Emergent laparotomy showed an enlarged spleen (1490 g, 23 × 16 × 7.5 cm) with laceration. Histologic evaluation showed atypical lymphoid cells positive for CD20 and cyclin D1, with strong p53 expression, negative for CD5 and SOX11, and a low Ki-67 index. Similar involvement was identified in the small bowel and appendix. Targeted sequencing of splenic tissue, performed as part of a retrospective molecular characterization, identified a pathogenic TP53 variant (p.His179Gln). Conclusions: This case provides a rare opportunity to evaluate splenic and small intestinal involvement by nnMCL at both the gross and histologic levels. It highlights the importance of integrating clinical findings with flow cytometry, imaging, cytogenetic, and molecular data in establishing the diagnosis. Even when peripheral blood findings suggest a low disease burden, imaging may better define the extent of disease and support appropriate clinical assessment, particularly in elderly patients at risk for complications related to splenomegaly. Full article

(This article belongs to the Special Issue Treatment and Prognosis of Hematological Malignancies)

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12 pages, 819 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Abstract

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

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

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16 pages, 1210 KB

Open AccessEditor’s ChoiceReview

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

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

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

Abstract

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

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

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15 pages, 1874 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Abstract

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

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

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