Haematologica

The LSC17 score: a prognostic biomarker now validated for real-world clinical application in acute myeloid leukemia

Michael Sandhu — 2025-12-04

The “morning cup of joe” as a modifiable factor in blood transfusion

Tiffany A. Thomas — 2025-10-16

The KLF4-CD46 axis: a novel therapeutic target in transplant-associated thrombotic microangiopathy and beyond

Massimo Cugno — 2025-10-09

Shedding light on the complicated world of alloreactive NK cells

Francesco Zorutti — 2025-11-13

The ABCs of donor selection: Availability Before Compatibility?

Brian C. Shaffer — 2025-11-13

The sobering reality of fertility preservation in young female patients with acute leukemia

Avraham Frisch — 2025-09-25

Romiplostim for aplastic anemia: beyond an eltrombopag alternative

Shinji Nakao — 2025-09-04

Diagnosis and management of adult telomere biology disorders

Madeline Franke — 2025-10-02

Telomere biology disorders (TBD) comprise a heterogenous group of inherited conditions characterized by impaired telomere maintenance, resulting in abnormal telomere lengths and/or telomere dysfunction. The clinical spectrum of TBD is broad, spanning bone marrow failure, pulmonary fibrosis, liver disease, and an increased predisposition to malignancy, complicating timely diagnosis and management. In this review, we explore the evolving clinical landscape and diagnostic strategies for TBD, while highlighting the diverse phenotypic presentations. We further examine the role of telomere dysfunction in driving cancer development and clonal hematopoiesis. Finally, we discuss current and emerging therapeutic approaches for TBD, emphasizing the need for individualized and multidisciplinary management to optimize patients’ outcomes.

Acute leukemia of ambiguous lineage: the known and the uncertain

Adi Sherban — 2025-10-09

Acute leukemia of ambiguous lineage (ALAL) is a rare, high-risk form of acute leukemia. It is characterized by the inability to assign a single lineage of differentiation to the leukemia and can manifest with more than one lineage-defining marker, called mixed phenotype acute leukemia (MPAL), or the complete absence of such markers, defined as acute undifferentiated leukemia (AUL). Recent genetic, epigenetic and metabolic insights refine diagnostic frameworks, inform classification and risk-stratification, and expose potential targetable vulnerabilities. However, the rarity and heterogeneous manifestations of ALAL result in ongoing diagnostic and therapeutic uncertainty. The most recent World Health Organization and International Consensus Classification documents provide a pragmatic framework integrating immunophenotypic and genetic criteria for classification, with recognition of specific somatic genetic alterations that define disease biology. These include rearrangements involving BCR::ABL1, KMT2A, ZNF384, and BCL11B activation. Current evidence supports the use of acute lymphoblastic leukemia-type induction regimens (with the addition of tyrosine kinase inhibitors for Philadelphia chromosome- positive MPAL) over acute myeloid leukemia or hybrid approaches. For AUL the optimal therapeutic approach is uncertain. Incorporation of targeted therapies in combination with intensive, and lower-intensity chemotherapy backbones based on the specific biological and genetic characteristics of ALAL is an appealing approach and is increasingly reported. The use of lineage-specific targeted approaches may result in therapeutic pressure and lineage switch in patients with acute leukemia with multi-phenotypic potential. The role and optimal platform for minimal residual disease surveillance in ALAL to guide therapy, and inform transplantation is unclear, given the paucity of prospective controlled data.

NFATc1 and NFATc2 regulate glucocorticoid resistance in pediatric T-cell acute lymphoblastic leukemia through modulation of cholesterol biosynthesis and the WNT/β-catenin pathway

Giulia Veltri — 2025-10-02

The glucocorticoid (GC) resistance onset in pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients remains one of the biggest challenges in current cancer treatment. The mechanisms driving this resistance are still not fully understood, making it difficult to predict patient outcomes and to develop effective therapies. Our study uncovered critical insights into the biological processes underlying GC resistance, offering potential breakthroughs for future treatments. Building on our previous research on lymphocyte cell-specific protein-tyrosine kinase (LCK) hyperactivation in GC-resistant T-ALL patients, we have now delved deeper into the LCK downstream nuclear factor of activated T cells (NFAT) transcription factor family’s contribution to GC resistance. We discovered that, even at the time of diagnosis, GC resistant T-ALL patients exhibit an intrinsic low glucocorticoid receptor (GR) activity coupled with high NFATc1 and NFATc2 activity. This dysregulation creates a roadblock to effective GC therapy. Indeed, in the absence of either NFATc1 or NFATc2, the normal transcriptional activity of GR is restored, re-sensitizing leukemia cells to dexamethasone treatment both in vitro and in vivo. This suggests that NFATc1 and NFATc2 are central to driving GC resistance, as they directly regulate crucial pathways like cholesterol biosynthesis and WNT/β-catenin signaling. The identification of NFAT transcription factors as key players in leukemia therapy resistance offers a promising target for future therapeutic strategies, potentially transforming the way we approach treatment for these challenging conditions or autoimmune disorders where glucocorticoids are a cornerstone of treatment.

Real-world validation study of the LSC17 score for risk prediction in patients with newly diagnosed acute myeloid leukemia

Tracy Murphy — 2025-07-10

Acute myeloid leukemia (AML) patients exhibit diverse molecular and cytogenetic changes with heterogeneous outcomes. The functionally-derived LSC17 gene expression score has demonstrated strong prognostic significance in retrospective analyses of adult and pediatric AML cohorts, where above-median scores are associated with worse outcomes compared to below-median scores in intensively-treated patients. Here we used a laboratory-developed clinically-validated NanoString-based LSC17 assay to test the prognostic value of the LSC17 score in a prospective multicenter study of 276 newly-diagnosed AML patients. Each patient’s score was classified as high or low by comparison to a previously-established reference score. In the entire cohort, a high LSC17 score was associated with poor risk features, including advanced age and unfavorable genetic mutations. In the subset of 190 patients treated intensively, a high LSC17 score was associated with lower remission rates (63% vs. 94% after induction; P<0.0001), presence of measurable residual disease (46% vs. 10%; P<0.0001), and shorter overall survival (OS, 606 days vs. not reached; P=0.0004; hazard ratio [HR] =2.16; 95% confidence interval [CI]: 1.39-3.35) and relapse-free survival (RFS, 541 days vs. not reached; P=0.001; HR=1.99; 95% CI: 1.29-3.08). In multivariable analysis considering age, white blood cell count and European LeukemiaNet 2022 risk groups, the LSC17 score remained an independent predictor of RFS and OS. Allogeneic stem cell transplantation improved OS for patients with a high but not a low LSC17 score. This study establishes the real-world value of the LSC17 score as a robust tool for risk assessment in AML and paves the way for its incorporation into routine clinical practice.

Clinical activity of venetoclax and azacitidine in children with de novo or secondary multiple relapsed/refractory acute myeloid leukemia: a real-world experience

Agathe Arcourt — 2025-10-16

Acute myeloid leukemia (AML) remains a major therapeutic challenge, particularly in relapsed or refractory patients, where prognosis is poor. The combination of venetoclax and azacitidine (ven/aza) has demonstrated significant efficacy in adults, yet evidence in pediatric populations is still limited and warrants further investigation. We conducted a multi-center retrospective analysis of 38 pediatric patients with relapsed/refractory (R/R) AML, including patients with de novo and secondary AML, treated with compassionate use ven/aza in four European countries between 2017 and 2023. Patient characteristics, AML-associated genetic alterations, treatment details, clinical responses, and adverse events with ven/aza therapy were analyzed. Among 38 children with R/R AML treated with ven/aza, the composite response rate (complete remission or complete remission with incomplete count recovery) was 26.3%. Median progression-free survival in responding patients was 22 months, and overall survival for the cohort was 6.1 months. Common ≥grade 3 toxicities included cytopenias (94%) and positive blood cultures (29%). This study demonstrates the real-world efficacy and tolerability of ven/aza in pediatric R/R AML. The regimen enabled remission and prolonged survival in select cases, with manageable toxicity and improved outpatient care. Findings support the need for pediatric trials to clarify therapeutic potential and identify predictive biomarkers.

Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity

Monika Dzieciatkowska — 2025-09-04

Caffeine is the most widely consumed psychoactive substance globally, yet its peripheral physiological effects remain incompletely understood. Leveraging comprehensive data from 13,091 blood donors in the REDS RBC-Omics study, we identified caffeine as a significant modulator of red blood cell (RBC) storage quality and transfusion outcomes. Elevated caffeine levels were reproducible across multiple donations from 643 recalled donors, selected based on their extremes in hemolytic propensity. Both in the screening and recalled cohorts, higher caffeine levels were associated with disrupted RBC metabolism, characterized by reduced glycolysis, depletion of adenylate pools or 2,3-bisphosphoglycerate, and increased markers of oxidative stress and osmotic fragility, including kynurenine accumulation. These observations were recapitulated in plasma and RBC of eight volunteers upon consumption of a cup of coffee independently of brewing method (Chemex vs. espresso). Clinically, elevated caffeine levels correlated with increased hemolysis and lower post-transfusion hemoglobin increments, an effect especially pronounced in recipients transfused with RBC from donors carrying common polymorphisms in the ADORA2B gene, a key regulator of RBC metabolism in hypoxia. These human findings were mechanistically validated using a murine model deficient in ADORA2b, which demonstrated impaired glycolytic flux, compromised antioxidant defenses (including caffeine-dependent direct inhibition of recombinantly expressed glucose 6-phosphate dehydrogenase), and decreased transfusion efficacy (lower hemoglobin increments, higher bilirubin after transfusion), effects further exacerbated by caffeine exposure during storage. Our study positions caffeine consumption as a modifiable factor in blood transfusion practice, advocating for precision strategies that integrate genetic and exposome factors, and identifies metabolic interventions to enhance blood quality and clinical outcomes.

Safety and efficacy of bridging radiation therapy prior to CD19 CAR T for non-Hodgkin lymphoma: a systematic review and meta-analysis

Mohammad Alhomoud — 2025-07-10

Bridging radiation therapy (BRT) is increasingly utilized prior to CD19-directed chimeric antigen receptor T cells (CART19) in patients with non-Hodgkin lymphoma (NHL). However, its impact on outcomes of CART19 therapy is not established. We conducted a systematic review and meta-analysis to estimate the safety and efficacy of BRT prior to CART19 therapy. A comprehensive search was performed in databases from inception to October 2024. We identified 18 studies encompassing 538 adult NHL patients who received BRT prior to commercial CART19. Random-effect models were applied to explore meta- analysis outcomes. Diffuse large B-cell lymphoma was the most common diagnosis (73%), and axicabtagene ciloleucel was the most utilized product (67%). Bulky disease was present in 37%. The median dose of BRT was 30 Gy delivered comprehensively to all sites of positron emission tomography-avid disease in 76% of cases. The overall response rate to CART19 was 78.9%. At 1 year, the progression-free survival was 54.6% while overall survival was 71.2%. All-grade cytokine release syndrome (CRS) developed in 80% of cases while all-grade immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 39.4%. The rate of grade 3/4 CRS was 3.6%, while that of grade 3/4 ICANS was 10.6%. Sensitivity analyses including studies with bulky disease and excluding studies with patients who also received systemic bridging therapy, demonstrated consistent results compared to the main study findings. Subgroup meta-regression showed similar results in studies that utilized BRT only compared to studies that utilized combined-modality treatment. In conclusion, this meta-analysis found that BRT use prior to CART19, whether as a standalone approach or in combination with systemic therapy, does not increase toxicity or compromise the efficacy of CART19 therapy in NHL. Furthermore, the use of BRT is associated with a low rate of CRS, even in patients with bulky disease.

MHC disparity hampers thymus-dependent T-cell recovery post-hematopoietic transplantation through dysregulation of TGF-β1 and LRP6 pathways

Ning Wu — 2025-09-25

Clinical studies have demonstrated that recipients of allogeneic hematopoietic cell transplantation (alloHCT), particularly those undergoing HLA-haploidentical alloHCT (haploHCT), exhibit significant immune deficiencies. However, the extent to which major histocompatibility complex (MHC) disparity independently contributes to the observed lymphocyte deficiency post-alloHCT remains unclear. While MHC matching is crucial for thymic selection of T lymphocytes, it has yet to be reported whether haploHCT alters recipient thymus homeostasis compared to MHC-matched HCT and which signaling pathways are implicated in this alteration. In this study, we established mouse models of MHC-matched HCT and haploHCT without any transplant-associated complications. Our findings indicated that MHC disparity significantly disrupted thymic architecture, suppressed thymus-specific gene expression, and resulted in impaired T-cell recovery and functionality following transplantation. Single-cell transcriptomic analysis revealed abnormally enhanced interactions involving TGFB1-TGFBR3 and LRP6-CKLF between thymic lymphocytes and epithelial cells in haploHCT recipients. Furthermore, agonists targeting the TGF-β1 and LRP6 pathways were found to compromise the functional characteristics of normal thymic T cells; conversely, appropriate inhibition of these pathways restored the differentiation and maturation phenotypes of thymic T cells derived from haploHCT recipients. Our study elucidates the independent role of MHC disparity in regulating thymus homeostasis and T-cell recovery while identifying the functional involvement of the TGF-β1 and LRP6 pathways in this context. These findings provide novel insights into the mechanisms underlying immune recovery as well as potential therapeutic strategies for modulating thymic functions following haploHCT.

Olverembatinib in accelerated-phase chronic myeloid leukemia: efficacy and safety evaluation

Mengyao Yuan — 2025-10-16

We studied 130 consecutive subjects who presented with (N=29) or transformed to (N=101) accelerated-phase chronic myeloid leukemia (CML) and who received olverembatinib. Sixty-two were in second chronic phase. All failed ≥1 tyrosine kinase inhibitor (TKI) and 91 had BCR::ABL1^T315I. Median follow-up was 28 months (interquartile range, 10-74 months). The 6-year cumulative incidences of major cytogenetic response (MCyR), complete cytogenetic response, major molecular response and molecular response 4.0 were 59% (95% confidence interval [CI]: 49- 69), 53% (95% CI: 42-62), 52% (95% CI: 41-62) and 42% (95% CI: 31- 53), respectively. The 6-year probabilities of transformation-free survival (TFS), CML-related survival and survival were 81% (95% CI: 72-90), 76% (95% CI: 67-87%) and 71% (95% CI: 61-82), respectively. In multi-variable analyses, an interval from diagnosis of CML to olverembatinib start <29 months, failure to achieve complete hematologic response on prior TKI therapy, hemoglobin concentration <98 g/L, blood and/or bone marrow blasts ≥8%, and/or high-risk additional chromosome abnormalities at the start of olverembatinib therapy, as well as not achieving early MCyR on olverembatinib correlated with worse outcomes. RUNX1 and STAT5A variants were significantly associated with worse TFS in the 82 subjects with targeted DNA-sequencing data. There were acceptable treatment-related adverse events. We conclude olverembatinib is effective and tolerable in subjects in accelerated-phase CML failing prior TKI therapy.

Interim analysis of a multicenter study on patient-guided dose reduction of tyrosine kinase inhibitors in chronic myeloid leukemia: the RODEO study

Dina Nienke Lokhorst — 2025-10-02

Patient-guided dose reduction, as explored in the RODEO study, offers a promising approach to alleviate the burden of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML). Supported by shared decision-making (SDM) and a patient decision aid, this strategy aims to reduce TKI toxicity while maintaining effectiveness. This interim analysis evaluates its effectiveness at six months, focusing on intervention failure, i.e., TKI dose re-escalation due to loss of major molecular remission (MMR) of BCR::ABL1 (>0.1%IS) or expected loss of MMR, and patient-reported health-related quality of life (HRQoL) and symptom burden. The SDM-process and decisional conflict are also evaluated. This is a prospective, single-arm, multicenter trial including 148 patients with chronic-phase CML in at least MMR. Patients and their treating hematologists were engaged in an SDM-process and selected a reduced TKI dose. BCR::ABL1 monitoring was conducted regularly; HRQoL and symptom burden was assessed using the scores of the QLQ-C30 and QLQ-CML24 questionnaires, and IL 156 item list. of the European Organisation for Research and Treatment of Cancer (EORTC). SDM and decisional conflict were evaluated via SDM-Q-9, SDM-Q-Doc, and the Decisional Conflict Scale. Of 146 patients analyzed, 2.8% experienced intervention failure at six months. Modest statistically significant improvements were seen in multiple symptom scales. SDM was well-evaluated, with low decisional conflict by patients. Patient-guided dose reduction appears safe and beneficial at six months follow-up.

Platelet-driven monocyte activation promotes hypoxic thromboinflammation through the HIF-1α-NLRP3-EGR-1 axis

Shankar Chanchal — 2025-10-09

Hypoxia exacerbates thromboembolism and sterile inflammation through the NLRP3 inflammasome, which is directly activated by HIF-1α, a factor that plays a pivotal role in potentiating deep vein thrombosis. One of the clinical manifestations of thromboinflammation is deep vein thrombosis, characterized by formation and propagation of a clot in the lower extremity of the body. The underlying inflammatory milieu promotes immune cell recruitment and platelet hyperactivation, further promoting a prothrombotic state. However, the intricate relationship between hypoxia, thromboembolism, and sterile inflammation is not fully understood. To address this knowledge gap, we integrated in vitro cell lines, ex vivo human peripheral blood mononuclear cells, in vivo animal models, and human patient-based studies to uncover the role of cellular interactions in driving hypoxia-induced thrombosis. We gained early mechanistic insights and subsequently tested the translational potential in humans who developed deep vein thrombosis at high altitudes (>11,000 feet). Our investigation revealed that hypoxia increased monocyte adhesion to endothelial surfaces, an effect mediated through CD11a/CD18 (β2 integrin) and F11R (junctional adhesion molecule-1; JAM-1). We determined the significance of the HIF-1α-NLRP3-Egr1-TF/ FVII axis in inflammation-induced coagulation under sterile conditions operating through NLRP3 elevating Egr-1, which subsequently augments tissue factor. This axis increases platelet hyperactivation and platelet association amplifying thromboinflammation. Human patients who developed high altitude thrombosis showed enhanced HIF-1α, NLRP3, Egr1, and TF/ FVII levels, confirming the clinical relevance of these factors. Finally, abrogating these molecules with either pharmacological inhibitors or siRNA demonstrated a potential to reverse these pathophysiological processes. These findings identify the HIF-1α-NLRP3-Egr1-TF/FVII axis as a potential therapeutic target for mitigating hypoxia-induced thromboinflammation.

Ex vivo correction of severe coagulation Factor VII deficiency in patient-derived 3D liver organoids

Giacomo Roman — 2025-10-09

Coagulation factor (F) VII deficiency is the most frequent among the rare, inherited bleeding disorders and is predominantly caused by missense mutations in the F7 gene. The disease phenotype ranges from asymptomatic cases to extremely severe hemorrhagic forms, requiring prophylactic injections with plasma-derived or recombinant FVII concentrates. In response, we have developed an autologous cell-based approach that corrects the disease-causing mutation in patient- derived induced pluripotent stem cells (iPSC) and generates therapeutic, three-dimensional hepatic organoids (HO). We report the CRISPR-mediated correction of homozygous c.718G>C (p.G240R), a missense mutation associated with a severe, life-threatening bleeding phenotype. The HO contain all liver cell types and exhibit key liver functions, including coagulation factor production. After correction, our data indicate that the patient-derived HO secrete consistent amounts of functional FVII protein, resulting in improved thrombin generation times. These results represent a significant milestone toward the establishment of an autologous cell-based therapy for patients with FVII- and other coagulation factor deficiencies.

KLF4 overexpression protects against complementmediated endothelial injury in transplant-associated thrombotic microangiopathy

Shuhui Jiang — 2025-08-07

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation, marked by excessive complement activation, endothelial injury, and microangiopathy. Although complement blockade benefits some patients, effective prophylactic and therapeutic strategies remain scarce. We, therefore, measured the levels of Krüppel-like factor 4 (KLF4), complement proteins and markers of endothelial injury in plasma samples from 20 TA-TMA patients and 1:1 matched control patients (matched by age, sex, underlying diagnosis, HLA compatibility, graft source, and donor-recipient ABO blood type). The KLF4-mediated regulatory mechanism was delineated through integrated in vitro and in vivo investigations. In this study, plasma analysis revealed that TA-TMA patients exhibit notably lower KLF4 levels compared to matched controls, as well as elevated levels of markers of endothelial injury. In vitro, increased KLF4 expression in human umbilical vein endothelial cells significantly reduced complement deposition and mitigated endothelial damage induced by TA-TMA plasma. Furthermore, KLF4 overexpression notably decreased apoptosis and preserved endothelial barrier integrity. In a mouse model of TA-TMA triggered by dimethyloxalylglycine, upregulation of KLF4 alleviated anemia, thrombocytopenia, and renal complement deposition, while diminishing endothelial inflammatory and thrombotic markers. Intriguingly, pravastatin treatment produced similar improvements. Mechanistic analyses using CUT&Tag, RNA sequencing, luciferase assays, and quantitative real-time polymerase chain reaction revealed that KLF4 binds to the CD46 promoter, enhancing its transcription and thus restraining complement activation in endothelial cells. These results identify KLF4 as a key negative regulator of complement-mediated endothelial injury in TA-TMA. This conclusion is supported by CD46 knockdown abolishing KLF4-mediated benefits, highlighting the therapeutic potential of targeting KLF4 or its downstream effectors, including CD46.

Integrating killer cell immunoglobulin-like receptor highresolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation

Antonia Schäfer — 2025-07-10

The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive natural killer cells through their killer cell immunoglobulin-like receptors (KIR). Conflicting results have been reported regarding the impact of the KIR immunogenetic system on HSCT outcomes with a scarcity of data interrogating the effect of KIR allelic polymorphism. With the aim of filling this gap, donor KIR genes derived from a national cohort of 1,247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient pairs bearing a KIR2DS4*00101–HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival, overall survival, transplant-related mortality and chronic graft-versus-host disease in multivariable analysis. Strong KIR2DL2/L3–HLA-C1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of chronic graft-versus-host disease compared to donor/recipient pairs with missing ligands. Strongly inhibiting KIR3DL1–HLA-B and HLA-A (Bw4) interactions were associated with a reduced relapse incidence as compared to weak and non-inhibiting interactions. Our study indicates that high-resolution KIR genotyping informs post-transplant outcomes with a seemingly higher protection of educated natural killer cells.

Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Jaime Sanz — 2025-07-31

There are conflicting data on the impact of mismatched unrelated donor (MMUD) compared to matched unrelated donor (MUD) in hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy), highlighting the need for disease-specific research. We conducted a retrospective analysis of donor characteristics in 350 patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) who received 8/8 human leukocyte antigen (HLA)-matched MUD and 7/8 HLA-matched MMUD. The primary endpoint was leukemia-free survival (LFS). The median age was 37 years (range, 18- 76), with 231 (66%) in first CR, and 280 (80%) diagnosed with B-cell ALL. The median donor age was 28 years (range, 18-57), with 237 (68%) MUD and 113 (32%) MMUD. The use of MUD or MMUD did not have a significant impact on LFS or other transplant outcomes. Among other donor-related variables, cytomegalovirus (CMV)-negative donor for a CMV-negative recipient was associated with improved LFS (Hazard Ratio [HR] 0.55; 95% Confidence Interval [CI]: 0.32-0.96) and overall survival (HR 0.52; 95% CI: 0.28-1), while older donor age showed an increased risk of acute graft-versus-host disease (aGvHD) grade III-IV (HR 1.7; 95% CI: 1.1-2.64) and female donor to male recipient combination increased the risk of grade II-IV aGvHD (HR 1.78; 95% CI: 1.05-3). In conclusion, non-HLA donor characteristics rather than HLA matching should be prioritized to guide unrelated donor selection for ALL patients in the PTCy HCT setting.

Loss of life expectancy in patients with myeloproliferative neoplasms in Sweden

Yuliya Leontyeva — 2025-09-25

Myeloproliferative neoplasms (MPN) are chronic bone marrow malignancies. While the prognosis is generally good, patients can face complications leading to reduced life expectancy. However, no population-based studies have quantified the life expectancy (LEC) and loss in life expectancy (LLE) following MPN. In this population-based study, we included individuals diagnosed with MPN in Sweden aged 50 years and older between 2002 and 2021, with follow-up until 2022. We used flexible parametric relative survival models with a period analysis (2012-2021) to estimate LEC and LLE. We also estimated 15-year restricted mean survival time (RMST) and the loss in 15-year restricted mean survival time (LRMST) for each MPN subtype: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The average LEC was 11.4 years (95% confidence interval [CI]: 11.2-11.7) and LLE was 4.3 years (95% CI: 4.1-4.6). For the MPN subtypes, the average 15-year LRMST was 1.8 (95% CI: 1.7-2.0) in PV, 1.3 (95% CI: 1.1-1.4) in ET, and 4.4 years (95% CI: 4.0-4.8) in PMF. Our study shows that life expectancy is lower in all MPN subtypes compared to the general population. By quantifying LEC and LLE, our research offers insights into the impact of MPN on an individual’s lifespan beyond the diagnosis.

A retrospective analysis of upfront treatment strategies in chronic myelomonocytic leukemia: impact on survival and response patterns

Muhammad Yousuf — 2025-10-16

In a retrospective analysis of 457 Mayo Clinic patients (median age 72 years) with chronic myelomonocytic leukemia (CMML) (proliferative 38%; CMML-2 15%), overall survival (OS), calculated from time of diagnosis, was not differentially affected by treatment exposure to: i) either cytotoxic or non-cytotoxic drugs (i.e., untreated; N=155; median 29 months); ii) non-cytotoxic drugs (N=95; median 25 months); iii) hydroxyurea (HU; N=102; median 23 months) or hypomethylating agent (HMA; N=78; median 35 months), as the first-line choice of cytotoxic therapy; or iv) cytotoxic drugs other than HU or HMA (N=27; median 18 months) (P=0.2). Blast transformation (BT) was more frequent in patients exposed to cytotoxic (26%) versus non-cytotoxic (11%) drugs (P<0.01), confirmed in multivariable analysis (HR [Hazard Ratio] 2.0; 95% Confidence Interval [CI]: 1.2-3.3) that accounted for other risk factors. Comparison of patients receiving HU or HMA favored HMA for control of leukocytosis (P<0.01), anemia (P=0.02), and thrombocytopenia (P=0.06); however, there was no difference in OS (P=0.3) or BTfree survival (P=0.7) between the two treatment arms. RUNX1 mutation was associated with lower response rates in leukocytosis (P=0.03) and thrombocytopenia (P=0.03) in HU/HMA treated patients. Allogeneic stem cell transplantation was undertaken in 49 patients with median post-transplant survival of 69 months. Our study confirms that current drug therapy in CMML has no impact on OS. Instead, it suggests a significant association between BT and the need for cytotoxic drug therapy. Our observations regarding higher response rates with HMA versus HU are also in line with a previously published controlled study.

Prognostic value of tumor bulk in modern management of common lymphoma subtypes: an Australasian Lymphoma and Related Diseases Registry study

Eliza Chung — 2025-09-25

The presence of a single large site of disease or so-called tumor ‘bulk’ in lymphoma has been variably associated with outcomes and influenced management decisions. However, challenges arise in using bulk as a prognosticator due to varied definitions across different lymphoma subtypes but also within studies of each subtype, increased utility of positron emission tomography in decision-making and recent incorporation of novel therapies. We analyzed data from the Australasian Lymphoma Registry regarding presence and influence of bulk on outcomes and treatment decisions in six key subtypes: diffuse large B-cell, follicular, marginal zone, T-cell, Hodgkin and Burkitt lymphoma. Of the 5,090 eligible patients identified between 2016-2025, 88% had documented information on the presence of bulk (registry definition >5 cm). Patients with bulk were more likely to receive systemic chemotherapy alone, and less likely to have localized treatment alone (radiotherapy and/or surgery), compared to those without bulk. Bulk was associated with inferior overall survival in patients with diffuse large B-cell lymphoma, and superior overall survival in those with Hodgkin lymphoma, in the univariate analyses. Exploratory analyses using disease-specific bulk definitions from clinicians practicing in Australia and New Zealand showed inferior progression-free survival in patients with diffuse large B-cell lymphoma (bulk >7.5 cm) and inferior overall survival in those with Burkitt lymphoma (bulk >10 cm), but not other subtypes. We demonstrated real-world evidence of management heterogeneity for patients with bulk, with potential prognostic implications. International standardization of the definition of bulk is urged for uniform utility in positron emission tomography-based and molecular prognostication across clinical studies. Trial registered with the Australian New Zealand Clinical Trials Registry: ANZCTRN12617000050358.

Hepatitis E virus infections in people with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches

Maximilian Al-Bazaz — 2025-09-25

Hepatitis E virus (HEV) is an under-recognized cause of viral hepatitis, with rising incidence in high-income countries largely driven by zoonotic transmission. Patients with multiple myeloma (MM) are especially vulnerable to HEV, yet there have been no recommendations for antiviral treatment or on its impact on the management of myeloma treatment. Here, we describe 7 patients (5 males, 2 females) with MM who were diagnosed with HEV infection at a tertiary care center in Western Europe within less than one year. All cases were confirmed by positive HEV RNA PCR in peripheral blood. Although no instances of fulminant hepatitis were observed, HEV prompted clinically relevant interruptions: autologous stem cell transplantation was postponed, lymphocyte apheresis for CAR T-cell manufacturing was delayed, and bispecific antibody regimens were suspended for up to five months. Ribavirin was initiated in 4 cases. The 3 patients undergoing T-cell-redirecting therapies, including one with prior ciltacabtagene autoleucel and 2 on bispecific antibodies, progressed to chronic infection despite ribavirin treatment. One patient, despite clearing HEV from peripheral blood, developed persistent vertigo and tested positive for HEV RNA in cerebrospinal fluid, indicating neuroinvasion. As the largest reported cohort of MM patients with HEV infections and the first to document chronic infection during treatment with T-cell-redirecting therapies, this study emphasizes the urgent need to increase awareness of HEV as an emerging threat, refine screening protocols at baseline or during unexplained aminotransferase flares, and to establish standardized therapeutic strategies in the era of novel immunotherapeutic approaches.

Brentuximab vedotin plus nivolumab as bridging therapy to CAR T-cells in relapsed/refractory primary mediastinal B-cell lymphoma

Armando Santoro — 2025-09-18

A founder heterozygous mutation in methyl-CpG binding domain protein 4 (MBD4) prevalent among Israeli Christian Arabs predisposes to increased mutagenesis

Gal Dadi — 2025-09-04

Blinatumomab restores asparaginase activity in pediatric B-cell acute lymphoblastic leukemia patients with PEGasparaginase hypersensitivity

Xue Tang — 2025-09-11

Ovarian tissue autotransplantation in acute leukemia: balancing the risk of relapse and the hope of parenthood

Florian Chevillon — 2025-07-10

Intravenous immunoglobulins in the management of acute chest syndrome in two Jehovah’s Witnesses with sickle cell disease

Francesca Begali — 2025-10-02

Wild-type p53 overexpression in NPM1-mutated acute myeloid leukemia: potential implications for disease biology and therapy response

Paul D. Barone — 2025-09-11

Safety and efficacy of romiplostim in children with acquired aplastic anemia who are naïve to immunosuppressive therapy

Mohammadreza Bordbar — 2025-07-24

Impact of demographic factors on clinical outcomes of patients with acute myeloid leukemia

Cassandra Duarte — 2025-09-11

Alterations in calreticulin and CD47 expression dynamics in myeloid malignancies: therapeutic and prognostic implications in myelodysplastic syndromes and myeloproliferative neoplasms

Kristian Boasman — 2025-09-25

Venetoclax plus hypomethylating agents as a bridge to transplant or donor lymphocyte infusion in relapsed/ refractory acute myeloid leukemia

Kathelijn Verdeyen — 2025-09-18

Impact of letermovir on cytomegalovirus-specific T-cell reconstitution after allogeneic hematopoietic stem cell transplantation in the post-transplant cyclophosphamide era

Elena Tassi — 2025-09-04

The co-inheritance of two ITGB3 variants with additive detrimental effects on platelets leads to variant Glanzmann thrombasthenia

Nina Arndt — 2025-09-25

Rapid and durable recovery of immune effector cells in myelofibrosis patients treated with momelotinib

Jasmine Makker — 2025-09-25

Real-world safety and efficacy of rADAMTS13 prophylaxis in congenital thrombotic thrombocytopenic purpura: experience from Polish patients previously treated with fresh frozen plasma

Jerzy Windyga — 2025-10-02

The added value of Bayesian interim analysis in randomized phase II and phase III clinical trials in hemato-oncology

Anna J.T. Smit — 2025-10-02

Utility of the Central Nervous System International Prognostic Index in patients with primary mediastinal large B-cell lymphoma treated with rituximab-containing chemoimmunotherapy

Jiayu Yang — 2025-10-02

Real-world safety and tolerability of rapid infusion obinutuzumab in chronic lymphocytic leukemia, small lymphocytic lymphoma and non-Hodgkin lymphoma: a provincial review

Harshal Senthil — 2025-10-09

Complete remission of bronchus-associated lymphoid tissue lymphoma after antibiotic treatment for Tropheryma whipplei

Teresa Antonia Kiener — 2025-11-27

Granuloma annulare-like pseudohistiocytosis: a specific manifestation of ETV6::SYK-rearranged myeloid neoplasm with eosinophilia

Giorgio Alberto Croci — 2025-11-20

Acute myeloid leukemia with t(10;17)(p15;q21)/ ZMYND11::MBTD1: a subtype with minimal differentiation, CD7/CD56 expression, and generally poor outcomes in adults

Qing Wei — 2025-11-20

Erratum to: “Lower incidence of chronic graft-versus-host disease after ruxolitinib plus extracorporeal photopheresis versus ruxolitinib alone in steroid-refractory acute graft-versus-host disease following allogeneic stem cell transplantation”

Iryna Lastovytska — 2026-03-01