HaematologicaPub Date : 2026-04-23DOI: 10.3324/haematol.2025.289111
Corinna Lutterbeck,Derrick Kaufman,Christopher R Bolen,Maria Shin,Vahid Akbari,Hamid Mirebrahim,Andrew Davies,Andrea Knapp,Tina Nielsen,Oliver Weigert,Elicia Penuel,Patrick E Bogard,Alessia Bottos
{"title":"Circulating tumor DNA at baseline as a prognostic marker in untreated follicular lymphoma.","authors":"Corinna Lutterbeck,Derrick Kaufman,Christopher R Bolen,Maria Shin,Vahid Akbari,Hamid Mirebrahim,Andrew Davies,Andrea Knapp,Tina Nielsen,Oliver Weigert,Elicia Penuel,Patrick E Bogard,Alessia Bottos","doi":"10.3324/haematol.2025.289111","DOIUrl":"https://doi.org/10.3324/haematol.2025.289111","url":null,"abstract":"Follicular lymphoma (FL) is an indolent disease with favorable outcome in patients with symptomatic disease treated with anti-CD20 based immunochemotherapy. However, a subset of patients experiencing progression within 24 months (POD24) have poor prognosis and shown shorter overall survival at 5 years. Identification of patients at high-risk that would benefit for alternative treatment is an unmet medical need, but available clinicogenetic scores show suboptimal performance for predicting early progression. We report a ctDNA analysis in baseline plasma from a large cohort of the global Phase-3 GALLIUM trial, which evaluated the efficacy of obinutuzumab plus chemotherapy versus rituximab plus chemotherapy in patients with untreated FL. We showed that ctDNA measured at baseline is prognostic for the identification of high-risk versus low-risk patients. In this large dataset, mutant molecules per milliliter (MMPM) adds prognostic value beyond known factors to predict POD24 (AUROC 0.69) compared to FLIPI (AUROC 0.57), FLIPI-2 (AUROC 0.59), and SPD (AUROC 0.58) in a univariate analysis, and consistently increased the AUROC of these scores in multivariate models. Using a cross-validated cutoff of 168.57 MMPM high baseline ctDNA was significantly associated with shorter progression free survival (HR = 2.2 [95% CI 1.8-2.6]). This prognostic value was maintained across CHOP or CVP and bendamustine regimens. These results provided a robust assessment of baseline ctDNA as stratification tool in clinical trials for patients treated with standard of care chemoimmunotherapy, and corroborates the growing scientific evidence proposing ctDNA as a novel prognostic biomarker for untreated FL.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"35 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brentuximab-vedotin and bendamustine for relapsed or refractory Hodgkin lymphoma: the LYSA real-world experience.","authors":"Gaetan Basile,Arnaud Neuville,Delphine Martineau,Baptiste Delapierre,Sydney Dubois,Robin Noel,Eric Durot,Adrien Caillet,Gaelle Labouré,Kamel Laribi,François-Xavier Gros,Sophie Bernard,Ariane Mineur,Cecile Borel,Loïc Chartier,Ghandi Damaj,Krimo Bouabdallah,Jean Galtier","doi":"10.3324/haematol.2025.300289","DOIUrl":"https://doi.org/10.3324/haematol.2025.300289","url":null,"abstract":"Classical Hodgkin lymphoma (HL) is often cured after modern first line regimen but relapsed or refractory (R/R) diseases remain a therapeutical challenge that has been addressed by little randomized clinical trials. Several combinations of brentuximab-vedotin (Bv) with chemotherapy have been reported in R/R HL so far, yet neither randomized clinical trials nor large scale real world evidence exist that comprehensively picture efficacy and toxicity of these distinct Bv-based regimen. By leveraging real-world data from 222 patients with R/R HL treated in France during 10 years, we showed that brentuximab-vedotin plus bendamustine (B2 regimen) was associated with an overall response rate (ORR), complete response (CR) rate and 2-year progression-free survival (2y-PFS) of 82%, 69.8% and 54.8%, respectively. The 2y-PFS of the 150 patients eligible for transplantation at B2 initiation was 64.2%, and reached 79.9% for the 102 patients in which transplantation was successfully performed, despite an infrequent use of Bv maintenance. Conversely and despite a CR rate of 69.6%, patients ineligible for transplantation faced poor outcomes with a 2y-PFS of 35%. B2 regimen was associated with low hematological toxicities and of neuropathy rates, and was administered as an outpatient treatment in 80% of cases. Considering the fact that Bv combinations might remain important therapy options for R/R diseases, notably after frontline regimen containing checkpoint inhibitors, these results support B2 regimen as a valid combination for patients eligible for transplantation while highlighting ineligible patients as a persistent unmet medical need.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"80 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2026-04-23DOI: 10.3324/haematol.2026.300560
Sudhir Tauro,Ayalew Tefferi
{"title":"Recovering from a therapeutic stall in higher-risk myelodysplastic syndromes: re-examining biology, backbones and study designs.","authors":"Sudhir Tauro,Ayalew Tefferi","doi":"10.3324/haematol.2026.300560","DOIUrl":"https://doi.org/10.3324/haematol.2026.300560","url":null,"abstract":"Therapeutic progress in higher-risk myelodysplastic syndromes (HR-MDS) has stalled. Despite repeated attempts to improve outcomes through incremental refinements to classification systems and hypomethylating agent (HMA)-based backbones, no phase 3 study since AZA-001 has replicated even the modest survival benefit observed with azacitidine. We propose that this stagnation results from a fundamental mismatch between the biological realities of HR-MDS and the assumptions underpinning contemporary drug development. HR-MDS encompasses biologically diverse ecosystems characterised by distinct clonal architectures, evolutionary trajectories and marrow microenvironmental dysfunction, despite overlapping phenotypic and genotypic features. Treating this heterogeneity as a single entity anchored to a hypomethylating agent backbone, risks obscuring therapeutic signals and misinterpreting responses. Here, we examine the potential biological, microenvironmental, and methodological drivers of therapeutic insufficiency in HR-MDS, to advocate for biologically coherent adaptive platform trials using biomarker-enriched patient selection, and propose shifting away from default HMA backbones. Only by redesigning strategy around biology, rather than prioritising ease of recruitment, or historical precedent, can we restore momentum and lift in HR-MDS drug development.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"144 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SQSTM1::RARA fusion in acute promyelocytic leukemia: the first case report and literature review.","authors":"Xiaomei Yin,Na Li,Zhanrui Cheng,Jia Ai,Hong Liang,Shu Sun,Hong-Hu Zhu","doi":"10.3324/haematol.2025.300329","DOIUrl":"https://doi.org/10.3324/haematol.2025.300329","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"1 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2026-04-23DOI: 10.3324/haematol.2025.289215
Guido Lancman, Dahniel Sastow, Minira Aslanova, Erin Moshier, Hearn Jay Cho, Sundar Jagannath, Samir Parekh, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa Sanchez, Santiago Thibaud, Ajai Chari
{"title":"Effect of intravenous immunoglobulin on infections in multiple myeloma patients receiving daratumumab.","authors":"Guido Lancman, Dahniel Sastow, Minira Aslanova, Erin Moshier, Hearn Jay Cho, Sundar Jagannath, Samir Parekh, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa Sanchez, Santiago Thibaud, Ajai Chari","doi":"10.3324/haematol.2025.289215","DOIUrl":"https://doi.org/10.3324/haematol.2025.289215","url":null,"abstract":"<p><p>Daratumumab is an anti-CD38 monoclonal antibody that has shown clinical benefit in both relapsed/refractory as well as newly diagnosed multiple myeloma (MM). Although daratumumab is very well-tolerated, randomized clinical trial data have consistently demonstrated an increased risk of infection, particularly along the respiratory tract, in patients receiving daratumumab. CD38 is present on healthy plasma cells, and their destruction can lead to hypogammaglobulinemia (HGG). In this study, we retrospectively reviewed all patients with MM treated with daratumumab and intravenous immunoglobulin (IVIG) at our institution from 2015-2019. The primary endpoints were the incidence rate ratios (IRR) of all-grade infections and grade 3-4 infections per patient-year during IVIG versus observation. In addition, a separate reference group of MM patients who were treated with daratumumab but never received IVIG was identified to establish baseline infection rates and to identify differences in baseline characteristics among patients who were selected to receive IVIG. A total of 43 patients received daratumumab and IVIG, primarily in the relapsed/refractory setting. All patients had HGG during treatment with daratumumab, with most (81%) experiencing moderate HGG (IgG.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HaematologicaPub Date : 2026-04-23DOI: 10.3324/haematol.2025.288819
Joanna Drozd-Sokolowska,Luuk Gras,Laurien G A Baaij,Linda Koster,Emma Nicholson,Peter Dreger,Tobias Gedde-Dahl,Stephan Mielke,Urpu Salmenniemi,Grzegorz Basak,Patrice Chevallier,Gerald G Wulf,Johannes Schetelig,Jan-Erik Johansson,Arnon Nagler,Stephanie Nguyen Quoc,Victoria Potter,Elisa Sala,Anna Bergendahl Sandstedt,Yener Koc,Robert Zeiser,Michel Van Gelder,Wieslaw Wiktor Jedrzejczak,Kavita Raj,Donal P McLornan,Olivier Tournilhac
{"title":"Long-term outcome of allogeneic hematopoietic cell transplantation for T-cell prolymphocytic leukemia - a study on behalf of the Chronic Malignancies Working Party of the EBMT.","authors":"Joanna Drozd-Sokolowska,Luuk Gras,Laurien G A Baaij,Linda Koster,Emma Nicholson,Peter Dreger,Tobias Gedde-Dahl,Stephan Mielke,Urpu Salmenniemi,Grzegorz Basak,Patrice Chevallier,Gerald G Wulf,Johannes Schetelig,Jan-Erik Johansson,Arnon Nagler,Stephanie Nguyen Quoc,Victoria Potter,Elisa Sala,Anna Bergendahl Sandstedt,Yener Koc,Robert Zeiser,Michel Van Gelder,Wieslaw Wiktor Jedrzejczak,Kavita Raj,Donal P McLornan,Olivier Tournilhac","doi":"10.3324/haematol.2025.288819","DOIUrl":"https://doi.org/10.3324/haematol.2025.288819","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"12 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune evasion in primary central nervous system lymphoma: macrophage and T cell roles in response to immunotherapy.","authors":"Carlota Pagès-Geli,Daniel Medina-Gil,Patricia Fernández-Guzmán,Cristina Hernández,Júlia Caràbia,Gemma Pujadas,Kipp Weiskopf,Francesc Bosch,Marta Crespo","doi":"10.3324/haematol.2025.300015","DOIUrl":"https://doi.org/10.3324/haematol.2025.300015","url":null,"abstract":"Primary central nervous system lymphoma is an aggressive extranodal lymphoma with poor prognosis, largely due to its capacity for immune evasion within the unique microenvironment of the CNS. Here, we investigated the interactions between macrophages and T cells in a syngeneic mouse model of PCNSL, manipulating macrophage/microglia populations and MHC class I expression on tumor cells to mimic patient-associated immune escape. We found that macrophages and microglia are indispensable for anti-tumor immunity and significantly enhance the efficacy of PD1 checkpoint blockade, particularly when tumor cells retain MHCI expression. In contrast, depletion of these myeloid cells led to accelerated disease progression and diminished response to immunotherapy, highlighting the importance of both innate and adaptive immunity in PCNSL. Interestingly, MHC-I-deficient PCNSL did not respond to T cell-based therapies and was controlled exclusively by macrophages, rendering prognosis largely dependent on this alteration. Our findings support the need for therapeutic strategies that target both T cell and myeloid compartments and suggest that profiling MHC-I expression may help guide personalized immunotherapy approaches in this challenging disease.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"25 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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