Haematologica
https://haematologica.org/
<p><strong>Open access journal of the Ferrata-Storti Foundation, a no profit organization. This journal was funded in 1920.</strong></p>Ferrata Storti Foundation, Pavia, Italyen-USHaematologica0390-6078Alessandro Pileri: an enthusiastic pioneer of modern hematology
https://haematologica.org/article/view/11917
Mario BoccadoroPaolo CorradiniMassimo MassaiaCorrado Tarella
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2025-02-012025-02-01110226726710.3324/haematol.2024.287046The origins of the definition of complete remission in acute myeloid leukemia
https://haematologica.org/article/view/11918
Mark R. Litzow
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2025-02-012025-02-01110226826910.3324/haematol.2024.286629Branching NOTCH1 to DNA damage in T-cell acute lymphoblastic leukemia
https://haematologica.org/article/view/haematol.2024.286450
Tanaya KulkarniDaniel Herranz
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2024-10-242024-10-24110227027210.3324/haematol.2024.286450Arkadia: a new player in hematopoietic stem and progenitor cell development
https://haematologica.org/article/view/11842
Sarada KetharnathanJason N. Berman
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2024-11-212024-11-21110227327510.3324/haematol.2024.286587Succinyl-coenzyme A: a key metabolite and succinyl group donor in erythropoiesis
https://haematologica.org/article/view/11827
Kevin Rouault-Pierre
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2024-11-142024-11-14110227627710.3324/haematol.2024.286672In T-follicular helper lymphomas, ‘one lymphoma can hide another’: beginning to explain
https://haematologica.org/article/view/11821
François LemonnierGaulard Philippe
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2024-11-142024-11-14110227828010.3324/haematol.2024.286173Introduction to the Review Series on Myelodysplasia
https://haematologica.org/article/view/haematol.2023.284948
Moshe Mittelman
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2025-01-272025-01-27110228128210.3324/haematol.2023.284948Pathogenesis and inflammaging in myelodysplastic syndrome
https://haematologica.org/article/view/haematol.2023.284944
<p>Myelodysplastic syndromes (MDS) are a genetically complex and phenotypically diverse set of clonal hematologic neoplasms that occur with increasing frequency with age. MDS has long been associated with systemic inflammatory conditions and disordered inflammatory signaling is implicated in MDS pathogenesis. A rise in sterile inflammation occurs with ageing and the term “inflammaging” has been coined by to describe this phenomenon. This distinct form of sterile inflammation has an unknown role in in the pathogenesis of myeloid malignancies despite shared correlations with age and ageing-related diseases. More recent is a discovery that many cases of MDS arise from clonal hematopoiesis of indeterminate potential (CHIP), an age associated, asymptomatic pre-disease state. The interrelationship between ageing, inflammation and clonal CHIP is complex and likely bidirectional with causality between inflammaging and CHIP potentially instrumental to understanding MDS pathogenesis. Here we review the concept of inflammaging and MDS pathogenesis and explore their causal relationship by introducing a novel framing mechanism of “pre-clonal inflammaging” and “clonal inflammaging”. We aim to harmonize research on ageing, inflammation and MDS pathogenesis by contextualizing the current understanding of inflammaging and the ageing hematopoietic system with what is known about the etiology of MDS via its progression from CHIP.</p>Matthew T. VillaumeMichael R. Savona
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2024-10-242024-10-24110228329910.3324/haematol.2023.284944Diagnosis of myelodysplastic syndromes: the classic and the novel
https://haematologica.org/article/view/haematol.2023.284937
<p>The myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by BM dysplasia, macrocytic anemia or cytopenia with a tendency for leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine laboratory findings, but the gold standard for the diagnosis of MDS is still BM examination with the presence of uni-or multi-lineage dysplasia and blast percentage, together with exclusion of other reasons. Cytogenetics is also a part of the diagnostic process. Flow cytometry and genetics are helpful but are not always mandatory for the diagnosis of MDS. This review summarizes the current steps in the diagnostic approach for a patient suspected of having MDS. We also describe new concepts that use non-invasive diagnostic technologies, especially digital methods as well as peripheral blood genetics. The hope is that one day these will mature, be introduced into clinical practice, and perhaps in many cases even replace the invasive BM biopsy.</p>Howard S. OsterArjan A. van de LoosdrechtMoshe Mittelman
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2024-10-242024-10-24110230031110.3324/haematol.2023.284937Genome sequencing in the management of myelodysplastic syndromes and related disorders
https://haematologica.org/article/view/haematol.2023.284947
<p>Myeloid neoplasms originate from the clonal proliferation of hematopoietic stem cells, which is driven by the acquisition of somatic genetic mutations. Within these disorders, myelodysplastic syndromes (MDS) are specifically characterized by morphological abnormalities (dysplasia) and impaired maturation of myeloid precursors (ineffective hematopoiesis), resulting in peripheral blood cytopenia. Several studies have advanced the field of MDS, with a few landmark papers leading to a paradigm shift, opening new avenues of research and enabling a molecular revolution. These seminal papers include the first description of the 5q- syndrome, the identification of somatic mutations of TET2 in myeloid neoplasms, the detection of common pathway mutations in the splicing machinery, and the discovery of clonal hematopoiesis. The somatic genomic landscape of MDS is now well defined. Genes that are recurrently mutated include epigenetic regulators, as well as genes of RNA splicing machinery, transcription regulation, DNA repair control, cohesin complex, and signal transduction. Furthermore, several disorders with a germline genetic predisposition to MDS have been identified, collectively accounting for up to 15% of all MDS cases. Genomic profiling can significantly improve the diagnostic approach to MDS, allowing the identification of distinct nosological entities such as SF3B1-mutant or TP53-mutant MDS. The Molecular International Prognostic Scoring System for MDS has already proven to be a valuable tool for individualized risk assessment and treatment decisions. In addition, the recently developed molecular taxonomy of MDS will likely facilitate the implementation of precision medicine approaches for these disorders. This will necessitate the establishment of specialized infrastructures within public health systems, involving close collaboration between healthcare institutions, academia, and the life-sciences industry.</p>Mario CazzolaLuca Malcovati
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2024-10-242024-10-24110231232910.3324/haematol.2023.284947Treatment of lower-risk myelodysplastic syndromes
https://haematologica.org/article/view/haematol.2023.284945
<p>Myelodysplastic syndromes (MDS) involve clonal hematopoiesis and cellular dysplasia, driven by genetic and epigenetic alterations. Spliceosome mutations and epigenetic dysregulation underscore the intricate pathogenesis of MDS. The bone marrow microenvironment, stromal dysfunction, chronic inflammation, and immune dysregulation contribute to disease progression. This complex pathogenesis underscores the necessity for targeted therapies, offering a personalized medicine approach, particularly in lower-risk patients. The development of risk scores such as the International Prognostic Scoring System (IPSS), its revision (IPSS-R), and the incorporation of molecular genetics into the IPSS-M have refined the diagnostic and prognostic framework of MDS. These scoring systems facilitate tailored treatment strategies and better prognostication, especially for lower-risk MDS patients. The progression from IPSS to IPSS-R and now to IPSS-M epitomizes the shift towards personalized medicine in the management of MDS. In this review we discuss recent developments and positive phase III studies in lower-risk MDS. The review concludes by proposing a treatment algorithm for lower-risk MDS and highlighting ongoing trials in this heterogeneous population of patients.</p>Almuth Maria Anni MerzUwe Platzbecker
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2024-10-242024-10-24110233033810.3324/haematol.2023.284945Treatment of high-risk myelodysplastic syndromes
https://haematologica.org/article/view/11858
<p>Myelodysplastic syndrome (MDS) is considered to be a heterogeneous myeloid malignancy with a common origin in the hematopoietic stem cell compartment and is generally divided into lower- and higher-risk forms. While the treatment goals for lower-risk MDS are to decrease transfusion requirements and transformation into acute leukemia, the major aims for higher-risk MDS are to prolong survival and ultimately cure the patient. Although novel agents such as luspatercept and imetelstat have recently been approved as new treatment options for lower-risk MDS, hypomethylating agents currently remain the only approved non-transplant option for higher-risk MDS and are the standard of care for patients not eligible for allogeneic hematopoietic stem cell transplantation (HSCT). Combinations with other drugs as first-line treatment have to date not proven more efficacious than monotherapy in higher-risk MDS, and outcome after the failure of treatment with hypomethylating agents is poor. The only potential cure and standard of care for eligible patients is HSCT and even though the number of transplanted – especially older – MDS patients has increased over time due to better management and greater donor availability, the majority of MDS patients will not be eligible for this curative approach. Current challenges include decreasing the relapse risk, the main cause of HSCT failure. This review summarizes current knowledge on the options of transplant and non-transplant treatment approaches for these patients and demonstrate the unmet clinical need for more effective therapies.</p>Nicolaus Kröger
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2024-12-052024-12-05110233934910.3324/haematol.2023.284946BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1
https://haematologica.org/article/view/haematol.2024.285552
<p>High levels of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) have been associated with tumor aggressiveness and drug resistance in several cancer types. Nevertheless, the mechanistic role of BCAT1 in T-cell acute lymphoblastic leukemia (T-ALL) remains uncertain. We provide evidence that Bcat1 was over-expressed following NOTCH1-induced transformation of leukemic progenitors and that NOTCH1 directly controlled BCAT1 expression by binding to a BCAT1 promoter. Further, using a NOTCH1 gain-of-function retroviral model of T-ALL, mouse cells genetically deficient for Bcat1 showed defects in developing leukemia. In murine T-ALL cells, Bcat1 depletion or inhibition redirected leucine metabolism towards production of 3-hydroxy butyrate (3-HB), an endogenous histone deacetylase inhibitor. Consistently, BCAT1-depleted cells showed altered protein acetylation levels which correlated with a pronounced sensitivity to DNA damaging agents. In human NOTCH1-dependent leukemias, high expression levels of BCAT1 may predispose to worse prognosis. Therapeutically, BCAT1 inhibition specifically synergized with etoposide to eliminate tumors in patient-derived xenograft models suggesting that BCAT1 inhibitors may have a part to play in salvage protocols for refractory T-ALL.</p>Valeria ToselloLudovica Di MartinoAdonia E. PapathanassiuSilvia Dalla SantaMarco PizziLara MussolinJingjing LiuPieter van VlierbergheErich Piovan
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2024-09-052024-09-05110235036710.3324/haematol.2024.285552Utilization of allogeneic hematopoietic stem cell transplantation among patients with newly diagnosed acute myeloid leukemia in California: a population-based linked dataset study
https://haematologica.org/article/view/haematol.2024.285648
<p>Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic / healthcare factors and use of alloHCT by age group (adolescent / young adult [AYA] 15-39 years, adult 40-64 years, older adult 65-79 years) using a linked dataset merging the Center for Internatonal Blood and Marrow Transplant Research, the California Cancer Registry, and the California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within two years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYA (49%). Factors statistically significantly associated with lower alloHCT utilization were: 1) AYA: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; 2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and 3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.</p>Christa L. MeyerTheresa H.M. KeeganAnn BrunsonJeffery J. AulettaLindsay M. MortonTed WunSara J. SchonfeldBryan ValcarcelRenata AbrahãoRafeek A. YusufLori Muffly
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2024-08-292024-08-29110236837710.3324/haematol.2024.285648Outcome of adult acute myeloid leukemia patients with extramedullary disease and treatment with venetoclax/hypomethylating agents
https://haematologica.org/article/view/haematol.2024.285985
<p>We evaluated response to venetoclax/hypomethylating agents (HMA) in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease. The median age of these patients was 65 years (range, 19-81). The patients had a median of two sites of extramedullary disease (range, 1-5) and 35 (76%) had concurrent bone marrow involvement. Twenty (43%) patients had high-risk genetic features according to the European LeukemiaNet 2022 classification. Twenty-nine (63%) had relapsed or were refractory after intensive chemotherapy, including 13 (28%) who had undergone prior allogeneic hematopoietic cell transplantation. Patients received a median of two cycles of venetoclax/HMA (range, 1-31). Twenty (43%) patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after venetoclax/HMA and five (11%) achieved a partial remission (PR). Six patients were subsequently consolidated with allogeneic hematopoietic cell transplantation (CR/CRi, N=4; PR, N=2). The median follow-up was 49.1 months (95% confidence interval [95% CI]: 26.1 months - not reached) and the median overall survival was 6.4 months (95% CI: 5.1-11 months). One-year and 2-year overall survival rates were 29.3% (95% CI: 18.6-46.2%) and 12.3% (95% CI: 5.5-27.6%), respectively. Age, with a cutoff of 60 years, did not have an impact on overall survival (P=0.90). Relapse occurred in 12 of 20 (60%) patients who achieved CR/CRi after venetoclax/ HMA treatment. Of those, all except one succumbed to their disease. Six (30%) patients were in CR/CRi at last follow-up and two (10%) died in CR. In our cohort of patients with AML with extramedullary disease with high-risk features, treatment with venetoclax/HMA resulted in an encouraging overall response rate of 54% with a CR/CRi rate of 43.5%. However, venetoclax/ HMA alone may not be effective in maintaining disease control.</p>Sabine KayserKhaled SanberGiovanni MarconiAgnese MatteiMarlise R. LuskinAmar KelkarMarco CerranoDaniel Tuyet KristensenAnne Stidsholt RougChiara SartorFabio GiglioMarta RivaLorenzo RizzoFrancesco SaraceniSelene GuerzoniFederica LessiErika BorlenghiMark J. LevisRichard F. SchlenkTania JainCristina Papayannidis
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2024-10-032024-10-03110237838410.3324/haematol.2024.285985Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish
https://haematologica.org/article/view/haematol.2024.285438
<p>The ubiquitination or SUMOylation of hematopoietic-related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase, is a newly discovered SUMO-targeted ubiquitin ligase involved in multiple signaling pathways mediated by transforming growth factor (TGF)-β family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impairment of hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111-deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-β signaling and downstream Smad2 phosphorylation, could restore definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and activation of the Gcsfr/NO signaling pathway.</p>Xiaohui LiuJinghan ShaLuxiang WangZixuan WangZhou FangXiao HanShuiyi TanYi ChenHao YuanHugues de TheJun ZhouJun Zhu
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2024-10-032024-10-03110238539610.3324/haematol.2024.285438Lysine succinylation precisely controls normal erythropoiesis
https://haematologica.org/article/view/haematol.2024.285752
<p>Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemic, precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation. To explore the functional significance of succinylation, we inhibited succinylation by either knocking down key succinyltransferases or overexpressing desuccinylases. Succinylation inhibition led to suppressed cell proliferation, increased apoptosis, and disrupted erythroid differentiation. In vivo overexpression of the desuccinylase SIRT5 delayed erythroid differentiation. Furthermore, integrative proteome and succinylome analysis identified 939 succinylated proteins with 3,562 Ksu sites, distributed across various cellular compartments and involved in multiple cellular processes. Significantly, inconsistencies were observed between protein expression levels and succinylation levels, indicating that the succinylation of certain proteins may function independently of expression. Mechanistically, we implicated KAT2A-mediated succinylation of histone H3 K79, leading to chromatin remodeling and, subsequently, regulation of erythropoiesis. Specifically, we identified CYCS as a key regulator of erythropoiesis, a function that depends on its succinylation sites K28/K40. Taken together, our comprehensive investigation of the succinylation landscape during erythropoiesis provides valuable insights into its regulatory role and offers potential implications for erythroid-related diseases.</p>Bin HuHan GongLing NieJi ZhangYanan LiDandan LiuHuifang ZhangHaihang ZhangLu HanChaoying YangMaohua LiWenwen XuYukio NakamuraLihong ShiMao YeChristopher D. HillyerNarla MohandasLong LiangYue ShengJing Liu
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2024-10-172024-10-17110239741310.3324/haematol.2024.285752Impact of soluble thrombomodulin and activated protein C on dynamic hemostatic function in trauma: a focus on thrombin generation and clot lysis
https://haematologica.org/article/view/haematol.2024.285951
<p>Trauma-induced coagulopathy describes a complex set of coagulation changes affecting severely injured patients. The thrombomodulin-protein C axis is believed to be central to the evolution of trauma-induced coagulopathy. Soluble thrombomodulin (sTM) levels are elevated after injury. Our objectives were to explore whether sTM (at concentrations found in patients after injury) plays an important role in trauma-induced coagulopathy, and specifically to evaluate the effects of sTM and activated protein C (APC) on thrombin generation (TG) and clot lysis time (CLT). Plasma from healthy volunteers was spiked with rising concentrations of sTM and APC and the effects on TG and CLT were analyzed. Plasma samples from a cohort of trauma patients were evaluated using TG and CLT, and results correlated to clinical parameters and factor VIII, factor V, APC, sTM and fibrinolytic measures. Increasing sTM concentrations in volunteer plasma led to reductions in endogenous thrombin potential and prolongation of 50% CLT, in a dose-dependent manner. No effect on TG or CLT was seen with rising APC concentrations. In 91 trauma patients, higher sTM values were associated with greater, rather than reduced, endogenous thrombin potential (median 1,483 vs. 1,681 nM/min) and longer 50% CLT (41.9 vs. 54.0 mins). In conclusion, sTM concentrations, across ranges found after trauma, affect both TG and 50% CLT, unlike APC. Despite increased circulating sTM levels, the overriding dynamic coagulation effects seen after injury are: (i) accelerated TG and (ii) increased rates of fibrinolysis. We found no evidence for sTM as the major determinant of the coagulation changes seen in early trauma-induced coagulopathy.</p>Nicola S. CurryJeries Abu-HannaGael B. MorrowRobin ChoudhuryMichael Laffan
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2024-09-052024-09-05110241442410.3324/haematol.2024.285951Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment
https://haematologica.org/article/view/haematol.2024.285304
<p>The activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell-like subtype (GCB-DLBCL). Currently, targeting the tumor microenvironment (TME) is the most promising approach to cure DLBCL with profound molecular heterogeneity; however, the factors affecting the tumor-promoting TME of ABC-DLBCL remain elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABC-DLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response, but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME, enhancing angiogenesis and the expression of cytokine IL-6 and IL-10, as well as decreasing T-cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in co-ordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumor-promoting effects of IL-16, providing new insights into treatment strategy in ABC-DLBCL.</p>Xuwen GuanYi WangTeng FangJingya WangRu LiMu HaoLugui Qiu
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2024-09-262024-09-26110242543810.3324/haematol.2024.285304Rituximab and lenalidomide for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma: real-life experience
https://haematologica.org/article/view/haematol.2024.285600
<p>The combination of rituximab and lenalidomide (R-len) stands as an established treatment for relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, the reproducibility of clinical trial results in routine clinical practice is unknown. To address this gap in knowledge, we reviewed our experience with patients diagnosed with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) treated with this combination. Eighty-four patients underwent treatment with R-len, 69 (82%) affected by FL and 15 (18%) by MZL. The median age at the time of treatment initiation was 65 years (range, 39-94), 38 patients (45%) had a pretreatment FLIPI score of 3-5, 19 (23%) had a bulky disease, 29 (37%) had a lymphoma refractory to the last treatment line, while in 20 (24%) cases the disease was refractory to rituximab. The best overall response rate was 82%, and 52% achieved a complete response (CR). The best CR rates for FL and MZL patients were 55% and 40%, respectively. With a median follow-up of 22 months, the median progression- free survival was 22 months (95% confidence interval [CI]: 19-36) and the 2-year overall survival was 83% (95% CI: 74-93). The median duration of CR was 46 months (95% CI: 22-not reached). Factors associated with shorter progression-free survival in multivariate analysis were bulky disease and rituximab refractoriness. The most common adverse events included hematologic toxicity, fatigue and gastrointestinal disorders, such as diarrhea and constipation. Neutropenia and thrombocytopenia were the most common severe toxicities (grade ≥3 in 25% and 4%, respectively). No new safety signals were reported. Real-life results of R-len in patients with R/R iNHL appear consistent with those reported in prospective studies, and further support its use as comparator arm in controlled clinical trials.</p>Giulio CassanelloEsther DrillAlfredo Rivas-DelgadoMichelle OkwaliIrem IsgorPhilip C. CaronZachary Epstein-PetersonPaola GhionePaul HamlinJennifer LueSteven M. HorwitzAndrew M. IntlekoferWilliam JohnsonAnita KumarAlison MoskowitzAriela NoyColette OwensLia M. PalombaPallawi TorkaPallavi GaleraAndrew D. ZelenetzGilles SallesLorenzo Falchi
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2024-09-052024-09-05110243944710.3324/haematol.2024.285600CODOX-M/IVAC-R <i>versus</i> DA-EPOCH-R in double-hit/triple-hit lymphoma patients aged 60 years or under
https://haematologica.org/article/view/haematol.2024.286168
<p>Intensified chemoimmunotherapy regimens are often used in young patients with double-hit and triple-hit lymphoma (DHL/ THL) despite no survival benefit compared to R-CHOP. Favorable retrospective reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate this treatment. We conducted a retrospective analysis to investigate outcome differences between CODOX-M/IVAC-R and DA-EPOCH-R in DHL/THL patients aged 60 years or younger. One hundred and thirteen patients were identified; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Eighty percent (39/49) achieved complete (CR) after completing CODOX-M/IVAC-R compared to 58% (37/64) with DA-EPOCH-R. The median follow-up was 5.3 years and 3.3 years for the CODOX-M/IVAC-R and DA-EPOCH-R group respectively. CODOX-M/IVAC-R demonstrated superior event-free survival (EFS) on univariate (hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.31-0.97) and multivariable analysis adjusted for age, BCL translocation (BCL2 vs. BCL6 vs. both), International Prognostic Index score and receipt of autologous stem cell transplant (adjusted HR [aHR]=0.52, 95% CI: 0.29-0.93); however there was no significant influence on OS (aHR=0.92, 95% CI: 0.46-1.84). The 1, 2 and 5 years EFS in the CODOX-M/IVAC-R group was 68.3%, 64.1% and 61.5%, respectively compared to 52.4%, 48.9% and 39.5%, respectively in the DA-EPOCH-R group. Primary refractory disease or relapse (R/R) occurred in 33% (16/49) of CODOX-M/IVAC-R and 54% (35/64) of DA-EPOCH-R recipients, and produced median OS of 10.3 months and 33.7 months, respectively, indicating poor outcomes in the CODOX-M/IVAC-R subgroup with R/R disease. More patients were able to receive subsequent salvage therapies in the DA-EPOCH-R group. No patients died of regimen toxicity and the rates of central nervous system relapse and therapy related hematologic neoplasms were similar in both groups.</p>Suheil Albert Atallah-YunesMatthew J. ReesThomas E. WitzigThomas M. HabermannJavier MunozMadiha IqbalEllen D. McPhailGrzegorz S. Nowakowski
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2024-10-102024-10-10110244845610.3324/haematol.2024.286168T-cell receptor architecture and clonal tiding provide insight into the transformation trajectory of peripheral T-cell lymphomas
https://haematologica.org/article/view/haematol.2024.285395
<p>While T-cell lymphomas are classified as mature neoplasms, emerging evidence indicates that malignant transformation may occur at an earlier stage of T-cell maturation. In this study, we determined clonal architecture in a broad range of T-cell lymphomas. Our multidimensional profiling indicates that many of these lymphomas do in fact emerge from an immature lymphoid T-cell precursor at a maturation stage prior to V(D)J rearrangement that undergoes branching evolution. Consequently, at single-cell resolution we observed considerable clonal tiding under selective therapeutic pressure. T-cell receptor next-generation sequencing suggested a highly biased usage of TRBV20-1 gene segments as part of multiple antigen receptor rearrangements per patient. The predominance of TRBV20-1 was found across all major T-cell lymphoma subtypes analyzed. This suggested that this particular V gene – independently of complementarity-determining region 3 configuration – may represent a driver of malignant transformation. Together, our data indicate that T-cell lymphomas are derived from immature lymphoid precursors and display considerable intratumoral heterogeneity that may provide the basis for relapse and resistance in these hard-to-treat cancers.</p>Edith WillscherChristoph SchultheißLisa PascholdFranziska Lea SchümannPaul Schmidt-BarboBenjamin ThieleMarcus BauerClaudia WickenhauserThomas WeberMascha Binder
Copyright (c) 2025 Ferrata Storti Foundation
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2024-08-292024-08-29110245746910.3324/haematol.2024.285395Safety and efficacy of human amniotic epithelial stem cell eye drops in ocular chronic graft-<i>versus</i>-host disease
https://haematologica.org/article/view/haematol.2023.284571
Xianjing ChengWei FanRuihao HuangYuancheng ZhaoYonghong TangShiqin HuangGuanghui ZhangXi ZhangRongdi YuanXiaoqi Wang
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-262024-09-26110247047410.3324/haematol.2023.284571Polytypic B cells, monotypic/monoclonal B-cell proliferations, and neoplastic T cells diverge from <i>TET2</i>-/<i>DNMT3A</i>-mutant clonal hematopoiesis in follicular helper T-cell lymphomas
https://haematologica.org/article/view/haematol.2024.285183
Natasha E. LewisKseniya Petrova-DrusRohan SardanaSarah HuetQi GaoShenon SethiChad VanderbiltWenbin XiaoMikhail RoshalJeeyeon BaikHimanshu BhurtelAlison J. MoskowitzSteven M. HorwitzAhmet Dogan
Copyright (c) 2025 Ferrata Storti Foundation
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2024-07-182024-07-18110247548010.3324/haematol.2024.285183Epigenetic age acceleration in hematopoietic stem cell transplantation
https://haematologica.org/article/view/haematol.2024.285291
Margherita UrsiKatarzyna Malgorzata KwiatkowskaChiara PirazziniGianluca StorciDaria MesselodiSalvatore Nicola BertuccioSerena De MatteisFrancesco IannottaEnrica TomassiniMarcello RobertoMaria NaddeoNoemi LaproviteraIrene SalamonBarbara SinigagliaElisa DanFrancesco De FeliceFrancesco BarbatoEnrico MaffiniSadia FalcioniMario ArpinatiManuela FerracinMassimiliano BonafèPaolo GaragnaniFrancesca Bonifazi
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-032024-10-03110248148410.3324/haematol.2024.285291Unraveling the germline inheritance of the <i>JAK2</i>F556V gene mutation in familial thrombocythemia: a comprehensive analysis of 11 family members and potential implications for surveillance
https://haematologica.org/article/view/haematol.2024.285329
Manja MeggendorferTorsten HaferlachMaria K. BeykirchPetro E. Petrides
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-262024-09-26110248548710.3324/haematol.2024.285329Tagraxofusp in combination with pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma shows encouraging preliminary efficacy with a manageable safety profile
https://haematologica.org/article/view/haematol.2024.285380
Paul RichardsonMyo HtutEmma ScottClaudia Paba PradaIra Gupta
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-032024-10-03110248849210.3324/haematol.2024.285380Evaluating serum free light chain ratio as a biomarker in multiple myeloma
https://haematologica.org/article/view/haematol.2024.285531
Theresia AkhlaghiKylee MaclachlanNeha KordeSham MailankodyAlexander LesokhinHani HassounSydney X. LuDhwani PatelUrvi ShahCarlyn TanAndriy DerkachOscar LahoudHeather J. LandauGunjan L. ShahMichael ScordoDavid J. ChungSergio A. GiraltSaad Z. UsmaniOla LandgrenMalin Hultcrantz
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-032024-10-03110249349710.3324/haematol.2024.285531Co-expression of CD69, CD49d, CD279 and CD20 in chronic lymphocytic leukemia cells is a new biomarker of active disease before or under therapy
https://haematologica.org/article/view/haematol.2024.285595
Sarah CadotLoïc YsebaertSébastien LamyCamille LaurentAnne Quillet-Mary
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-262024-09-26110249850310.3324/haematol.2024.285595Adverse clinical outcomes associated with sickle cell trait at high altitude
https://haematologica.org/article/view/haematol.2024.285832
Katherine A. StaffordSoravis OsataphanRushad PatellNigel S. Key
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-032024-10-03110250450610.3324/haematol.2024.285832Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myelomareactive CD8<sup>+</sup> T cells are shared between blood and marrow
https://haematologica.org/article/view/haematol.2024.285952
James FavaloroChristian E. BryantEdward AbadirSamuel GardinerShihong YangTracy KingNajah NassifBronwyn A. O’BrienLisa M. SedgerRichard BoyleDouglas E. JoshuaP. Joy Ho
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-032024-10-03110250751310.3324/haematol.2024.285952BET inhibitors downregulate the expression of the essential lncRNA <i>SMILO</i> in multiple myeloma through regulation of the transcription factor FLI1
https://haematologica.org/article/view/haematol.2024.285966
Nahia Gómez-EcharteEdurne San José-EnérizArantxa Carrasco-LeónNaroa BarrenaEstibaliz MirandaLeire GarateBeatriz García-TorreSandra Alonso-MorenoNaroa Gimenez-CaminoEstibaliz Urizar-CompainsDanel Olaverri-MendizabalPaula Aguirre-RuizBeñat AricetaLuis-Esteban Tamariz-AmadorPaula Rodriguez-OteroFrancisco J. PlanesLaura BelverJosé Ignacio Martín-SuberoFelipe ProsperXabier Agirre
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-262024-09-26110251451910.3324/haematol.2024.285966Intra-marrow delivery of human interleukin-6-loaded biodegradable microspheres promotes growth of patientderived multiple myeloma cells in mice
https://haematologica.org/article/view/haematol.2024.285980
Manpreet BarianaWeiwei WangZhuozhuo YinJingyu SunShabnam SamimiShaina A. AnuncioElena CassellaNuo XuWei HuAriel AptekmannDavid S. SiegelKar F. ChowHongjun WangJohannes L. Zakrzewski
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-122024-09-12110252052610.3324/haematol.2024.285980Susceptibility to BK polyomavirus-associated hemorrhagic cystitis in children undergoing allogeneic transplant
https://haematologica.org/article/view/haematol.2024.286163
Sheyar AbdullahAnthony SabulskiZahra HuddaAssem ZiadyNathan LuebberingLucy GiordulloElizabeth OdegardJason T. BlackardSteve KleiboekerMichelle AltrichSonata JodeleAlix E. SeifStella M. DaviesBenjamin L. Laskin
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-192024-09-19110252753110.3324/haematol.2024.286163Adopting the new iStopMM-based criteria for light-chain monoclonal gammopathy of undetermined significance: an ongoing debate
https://haematologica.org/article/view/haematol.2024.286239
Dor ShpitzerYael C. CohenTamir ShragaiGuy MelamedAnat Reiner-BenaimIrit Avivi
Copyright (c) 2025 Ferrata Storti Foundation
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2024-09-122024-09-12110253253510.3324/haematol.2024.286239Artificial intelligence-based Myelodysplastic Syndromes Score, 2022 classifications, and the Molecular International Prognostic Scoring System: a perfect match
https://haematologica.org/article/view/haematol.2024.286340
Valentin ClichetThomas Boyer
Copyright (c) 2025 Ferrata Storti Foundation
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2024-10-102024-10-10110253653910.3324/haematol.2024.286340