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> en-US office@haematologica.org (Haematologica) office@haematologica.org (Haematologica) Wed, 01 Jan 2025 10:37:48 +0000 OJS 3.1.2.4 http://blogs.law.harvard.edu/tech/rss 60 The CLL hunters: finally, BTK got arrested https://haematologica.org/article/view/11881 Loic Ysebaert Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/11881 Wed, 01 Jan 2025 00:00:00 +0000 Hematopoietic cell transplantation soon after first relapse in acute myeloid leukemia – the PROS https://haematologica.org/article/view/haematol.2024.286063 Edward Copelan, Robert P. Gale Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286063 Wed, 01 Jan 2025 00:00:00 +0000 Hematopoietic cell transplantation soon after first relapse in acute myeloid leukemia – the CONS https://haematologica.org/article/view/11883 Yishai Ofran, Jacob M. Rowe Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/11883 Wed, 01 Jan 2025 00:00:00 +0000 Pirtobrutinib: the ‘brute’ with a softer side https://haematologica.org/article/view/haematol.2024.286532 Justin Desroches, Diego Villa Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286532 Thu, 17 Oct 2024 00:00:00 +0000 LIPA-frogging blast phase chronic myeloid leukemia: hopping over resistance with lysosomal targeting https://haematologica.org/article/view/haematol.2024.286140 Miguel Quijada-Álamo, Grace Freed, Elvin Wagenblast Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286140 Thu, 22 Aug 2024 00:00:00 +0000 Challenges in defining the immune microenvironment in T-cell lymphoma https://haematologica.org/article/view/haematol.2024.285836 Ahmet Dogan, Mikhail Roshal Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285836 Thu, 10 Oct 2024 00:00:00 +0000 Help or hindrance? Rituximab maintenance and COVID https://haematologica.org/article/view/haematol.2024.286142 Ariela Noy Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286142 Thu, 12 Sep 2024 00:00:00 +0000 The real world of acute lymphoblastic leukemia https://haematologica.org/article/view/haematol.2024.286346 Mark R. Litzow Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286346 Thu, 05 Sep 2024 00:00:00 +0000 Chronic myelomonocytic leukemia: molecular pathogenesis and therapeutic innovations https://haematologica.org/article/view/haematol.2024.286061 <p>Chronic myelomonocytic leukemia (CMML) is an aggressive clonal stem cell disorder categorized among myelodysplastic/ myeloproliferative overlap neoplasms. While sharing features with both myelodysplastic syndromes and myeloproliferative neoplasms, CMML has distinct molecular and clinical profiles. The presence of CMML-specific prognostic models, response criteria, and dedicated clinical trials underscores a unique and complex biology. Age-related changes affecting the bone marrow microenvironment, immune responses, and the intricate balance between epigenetic deregulation and proinflammatory signaling are characteristic of this disease, collectively posing significant scientific and clinical challenges in its management. CMML is an aging-related, clinically heterogeneous neoplasm with limited approved therapeutic options, representing an area of unmet medical need. This review offers a comprehensive analysis of the current understanding of the molecular mechanisms driving CMML evolution and its clinical manifestations within the ever-evolving landscape of precision medicine. In light of the most recent molecular discoveries, we highlight the shortcomings of existing therapies and underscore promising investigational agents. Many of the biological findings discussed are shared across a spectrum of acute and chronic myeloid neoplasms, as well as clonal hematopoiesis, broadening the scope of this review.</p> Ludovica Marando, Clifford M. Csizmar, Mrinal M. Patnaik Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286061 Thu, 17 Oct 2024 00:00:00 +0000 T-cell clones of uncertain significance. When is the rogue clone dangerous? https://haematologica.org/article/view/haematol.2024.286023 <p>T-cell large granular lymphocyte clones that persist over time and that exhibit molecular and immunophenotypic features closely resembling those of T-cell large granular lymphocyte leukemia (T-LGLL) may be detectable in individuals who lack any clinical or laboratory features supporting a diagnosis of a T-cell malignancy. This condition represents a potential precursor state termed T-cell clones of uncertain significance (T-CUS). T-CUS represents the even more benign extreme of the wide spectrum of clonal T-large granular lymphocyte proliferations, emphasizing the need for an appropriate multiparametric diagnostic assessment that avoids misdiagnosis of T-cell neoplasia. This approach should overcome numerical cut-offs as the sole criteria to differentiate the benign condition from the related malignancies. In particular, genomic aberrancies might prospectively identify individuals who are at risk of progression to a full-blown T-cell malignancy. We herein discuss the significance of these T-cell clones in both healthy and disease states, suggesting molecular assays for tracking early steps of disease.</p> Gianpietro Semenzato, Antonella Teramo, Giulia Calabretto, Renato Zambello Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286023 Thu, 03 Oct 2024 00:00:00 +0000 Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: results of a multicenter randomized trial https://haematologica.org/article/view/haematol.2024.285428 <p>Infections lead to substantial morbidity during the treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system is severely affected, leading to declining serum immunoglobulin levels. We performed a trial to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL could prevent admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium-risk ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every 3 weeks, starting on day 22 after diagnosis) or well-defined standard of care (control group). Between October 2012 and March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (P=0.011). IVIG prophylaxis was not associated with bacteremia. However, there were significantly fewer admissions for fever with negative blood cultures in the IVIG prophylaxis group than in the control group (113 vs. 200, P&lt;0.001). The difference in number of admissions for fever was observed specifically during maintenance treatment (100 vs. 166, P&lt;0.001) resulting in fewer courses of antibiotic treatment (78 vs. 137, P&lt;0.001) and fewer cases of chemotherapy adaptation (72 vs. 134, P&lt;0.001). In conclusion, in pediatric patients with medium-risk ALL, IVIG prophylaxis was associated with significantly fewer admissions for fever with negative blood cultures during maintenance treatment, resulting in fewer courses of antibiotic treatment and fewer chemotherapy adaptations.</p> Kirsten A. Thus, Hester A. de Groot-Kruseman, Pauline Winkler-Seinstra, Marta Fiocco, Heidi Segers, Cor van den Bos, Inge M. van der Sluis, Wim J.E. Tissing, Margreet A. Veening, Christian Michel Zwaan, Cornelis M. van Tilburg, Rob Pieters, Marc Bierings Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285428 Thu, 08 Aug 2024 00:00:00 +0000 Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study https://haematologica.org/article/view/haematol.2024.285638 <p>The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL) has significantly improved patients’ prognosis. Within the Campus ALL network, we analyzed the outcome of adult Ph- ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial to compare the real-life data with the study results. We included 421 consecutive patients; median age 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94%, and measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high-risk (VHR) and MRD positive cases, transplanted (hematopoietic stem cell transplantation [HSCT]) patients had a significantly better DFS than non-HSCT patients (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs. 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large, real-life cohort of Ph- ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial (CR rate after C1, 94% vs. 85%, P=0.0004; 3-year OS, 67% vs. 67%, P=0.94; 3-year DFS, 57% vs. 63%, P=0.17). HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.</p> Davide Lazzarotto, Marco Cerrano, Cristina Papayannidis, Sabina Chiaretti, Federico Mosna, Nicola Fracchiolla, Patrizia Zappasodi, Silvia Imbergamo, Maria Ilaria Del Principe, Monia Lunghi, Federico Lussana, Matteo Piccini, Monica Fumagalli, Michelina Dargenio, Prassede Salutari, Fabio Forghieri, Teresa Giulia Da Molin, Massimiliano Bonifacio, Matteo Olivi, Fabio Giglio, Silvia Trappolini, Matteo Leoncin, Antonino Mule, Mario Delia, Crescenza Pasciolla, Francesco Grimaldi, Benedetta Cambo, Lidia Santoro, Fabio Guolo, Paola Minetto, Marzia Defina, Patrizia Chiusolo, Matteo Fanin, Endri Mauro, Lara Aprile, Carla Mazzone, Fabio Trastulli, Maria Ciccone, Marco De Gobbi, Alessandro Cignetti, Eleonora De Bellis, Valentina Mancini, Alfonso Piciocchi, Marco Vignetti, Giovanni Marsili, Irene Della Starza, Renato Fanin, Mario Luppi, Felicetto Ferrara, Giovanni Pizzolo, Renato Bassan, Robin Foa, Anna Candoni Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285638 Thu, 15 Aug 2024 00:00:00 +0000 Hematopoietic cell transplantation for older acute myeloid leukemia patients in first complete remission: results of a randomized phase III study https://haematologica.org/article/view/haematol.2024.285879 <p>Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/low-dose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to 5 years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (N=83) or non-HCT (N=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95% confidence interval [CI]: 18.9-30.1) in the HCT and 15.6 months (95% CI: 10.4-20.8) in the non-HCT arm (P=0.022) due to a decrease in cumulative relapse incidence from 91.1% (95% CI: 80.7-100.0) after non-HCT to 37.8% (95% CI: 27.2-48.4) after HCT (P&lt;0.0001). The secondary endpoints RM-OS up to 5 years was 27.8 months (95% CI:22.3-33.2) in the HCT as compared to 28.6 months (95% CI: 22.2-35.0) in the non-HCT arm; non-relapse mortality at 5 years was 33.4% (95% CI: 23.0-43.9) with HCT and 0% without. In older patients with AML in CR1 5-year RM-LFS is better with HCT than with non-HCT consolidation treatment. The long-term RM-LFS benefit did not translate into a better RM-OS during the study period.</p> Dietger Niederwieser, Dirk Hasenclever, Wolfgang E. Berdel, Bart J. Biemond, Haifa Al-Ali, Yves Chalandon, Michel van Gelder, Christian Junghanß, Gösta Gahrton, Mathias Hänel, Rüdiger Hehlmann, Thomas Heinicke, Andreas Hochhaus, Simona Iacobelli, Rien van Marwijk Kooy, Nicolaus Kröger, Jeroen Janssen, Madlen Jentzsch, Frank Breywisch, Mohamad Mohty, Stavroula Masouridi-Levrat, Gert Ossenkoppele, Jacob Passweg, Wolfram Pönisch, Johannes Schetelig, Christoph Schliemann, Sebastian Schwind, Matthias Stelljes, Leo F. Verdonck, Vladan Vucinic, Bob Löwenberg, Jan Cornelissen Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285879 Thu, 08 Aug 2024 00:00:00 +0000 LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia https://haematologica.org/article/view/haematol.2023.284353 <p>Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax-naïve and -resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax-responsive and -relapsed CLL.</p> Janani Ravikrishnan, Daisy Y. Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D. Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, KerryA Rogers, Adam S. Kittai, Seema A. Bhat, Mary C. Collins, Matthew S. Davids, Nitin Jain, William G. Wierda, Rosa Lapalombella, John C. Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P. Anthony, Jennifer A. Woyach, Deepa Sampath Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2023.284353 Thu, 08 Aug 2024 00:00:00 +0000 Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial https://haematologica.org/article/view/haematol.2024.285754 <p>Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase I/II BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with relapsed / refractory B-cell malignancies (clinicaltrials.gov 03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (N=40, 31.5%), specifically atrial fibrillation (N=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common reasons for pirtobrutinib discontinuation were progressive disease (26.8%), AE (10.2%) or death (5.5%). The most frequent treatment-emergent AE were fatigue (39.4%) and neutropenia (37.0%). Among patients who discontinued a prior BTKi for a cardiac issue, 75% had no recurrence of their cardiac AE. No patient discontinued pirtobrutinib for the same AE that led to discontinuation of the prior BTKi. In 78 chronic lymphocytic / small lymphocytic lymphoma (CLL/SLL) and 21 mantle cell lymphoma (MCL) patients intolerant to prior BTKi, overall response rate to pirtobrutinib was 76.9% and 81.0%, respectively. Median progression-free survival for CLL/SLL was 28.4 months but was not estimable for MCL. These results suggest that pirtobrutinib was safe, well-tolerated, and an efficacious option in patients with prior BTKi-intolerance.</p> Nirav N. Shah, Michael Wang, Lindsey E. Roeker, Krish Patel, Jennifer A. Woyach, William G. Wierda, Chaitra S. Ujjani, Toby A. Eyre, Pier Luigi Zinzani, Alvaro J. Alencar, Paolo Ghia, Nicole Lamanna, Marc S. Hoffmann, Manish R. Patel, Ian Flinn, James N. Gerson, Shuo Ma, Catherine C. Coombs, Chan Y. Cheah, Ewa Lech-Maranda, Bita Fakhri, Won Seog Kim, Minal A. Barve, Jonathon B. Cohen, Wojciech Jurczak, Talha Munir, Meghan C. Thompson, Donald E. Tsai, Katherine Bao, Nicholas A. Cangemi, Jennifer F. Kherani, Richard A. Walgren, Hongmei Han, Amy S. Ruppert, Jennifer R. Brown Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285754 Thu, 03 Oct 2024 00:00:00 +0000 Lysosomal acid lipase A modulates leukemia stem cell response to venetoclax/tyrosine kinase inhibitor combination therapy in blast phase chronic myeloid leukemia https://haematologica.org/article/view/haematol.2023.284716 <p>The treatment of blast phase chronic myeloid leukemia (bpCML) remains a challenge due, at least in part, to drug resistance of leukemia stem cells (LSC). Recent clinical evidence suggests that the BCL-2 inhibitor venetoclax in combination with ABL-targeting tyrosine kinase inhibitors can eradicate bpCML LSC. In this study, we employed preclinical models of bpCML to investigate the efficacy and underlying mechanism of LSC-targeting with combinations of venetoclax/tyrosine kinase inhibitors. Transcriptional analysis of LSC exposed to venetoclax and dasatinib revealed upregulation of genes involved in lysosomal biology, in particular lysosomal acid lipase A (LIPA), a regulator of free fatty acids. Metabolomic analysis confirmed increased levels of free fatty acids in response to treatment with venetoclax/dasatinib. Pretreatment of leukemia cells with bafilomycin, a specific lysosome inhibitor, or genetic perturbation of LIPA, resulted in increased sensitivity of leukemia cells to venetoclax/dasatinib, implicating LIPA in treatment resistance. Importantly, venetoclax/dasatinib treatment did not affect normal stem cell function, suggesting a leukemia-specific response. These results demonstrate that venetoclax/dasatinib is a LSC-selective regimen in bpCML and that disrupting LIPA and fatty acid transport enhances the response to venetoclax/ dasatinib when targeting LSC, providing a rationale for exploring lysosomal disruption as an adjunctive therapeutic strategy to prolong disease remission.</p> Mohd Minhajuddin, Amanda Winters, Haobin Ye, Shanshan Pei, Brett Stevens, Austin Gillen, Krysta Engel, Stephanie Gipson, Monica Ransom, Maria Amaya, Anagha Inguva, Maura Gasparetto, Mark J. Althoff, Regan Miller, Ian Shelton, Hunter Tolison, Anna Krug, Rachel Culp-Hill, Angelo D’Alessandro, Daniel W Sherbenou, Daniel A. Pollyea, Clayton Smith, Craig T Jordan Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2023.284716 Thu, 27 Jun 2024 00:00:00 +0000 Single-cell proteo-transcriptomic profiling reveals altered characteristics of stem and progenitor cells in patients receiving cytoreductive hydroxyurea in early-phase chronic myeloid leukemia https://haematologica.org/article/view/haematol.2024.285071 <p>Hydroxyurea (HU) is frequently used in the early phase of chronic myeloid leukemia (CML) to achieve cytoreduction prior to tyrosine kinase inhibitor therapy. However, its impact on CML stem and progenitor cells (SPC) remains largely unknown. This study utilized targeted proteo-transcriptomic expression data on 596 genes and 51 surface proteins in 60,000 CD14-CD34+ cells from chronic phase CML patients to determine effects of short-term HU treatment (4-19 days) on CML SPC. Peripheral blood and bone marrow samples were obtained from 17 CML patients eligible for short-term HU treatment (3 patients before and after HU, 7 patients before HU and 7 patients after HU) and subjected to single-cell CITE-sequencing and/or flow cytometry analysis. The analysis revealed enhanced frequencies of hemoglobin-expressing (HBA1, HBA2, HBB) erythroid progenitor cells in blood and bone marrow following HU treatment. In addition, there was an accumulation of cell subsets with S/G2/M phase-related gene and protein expression, likely representing cells arrested in, or progressing slowly through, the cell cycle. The increased frequency of cells in S/G2/M phase after HU was observed already among the most immature leukemic stem cells (LSC), and patients with a large fraction of LSC in the S/G2/M phase showed poor responsiveness to tyrosine kinase inhibitor treatment. We conclude that short-term HU treatment entails differentiation of erythroid progenitor cells and alters the characteristics of LSC in CML. The results imply that studies of LSC and progenitor populations in CML should take effects of initial HU therapy into account.</p> Hana Komic, Malin S. Nilsson, Lovisa Wennström, Tagore Sanketh Bandaru, Pekka Jaako, Kristoffer Hellstrand, Fredrik B. Thorén, Anna Martner Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285071 Thu, 15 Aug 2024 00:00:00 +0000 Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets https://haematologica.org/article/view/haematol.2023.284448 <p>Whereas immunotherapies have revolutionized the treatment of different solid and hematologic cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCL) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCL, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analysis on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCL, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor.</p> Pierre Stephan, Jimmy Perrot, Allison Voisin, Maud Barbery, Thibault Andrieu, Maxime Grimont, Julie Caramel, Mathilde Bardou, Garance Tondeur, Edoardo Missiaglia, Philippe Gaulard, François Lemmonier, Laurence de Leval, Emmanuel Bachy, Pierre Sujobert, Laurent Genestier, Alexandra Traverse-Glehen, Yenkel Grinberg-Bleyer Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2023.284448 Thu, 30 May 2024 00:00:00 +0000 Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma https://haematologica.org/article/view/haematol.2024.285185 <p>Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) transformed from indolent B-cell lymphomas, including Richter transformation, have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates in B-cell non-Hodgkin lymphoma as monotherapy but may synergize with immunogenic chemotherapies such as gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including Richter transformation. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to four cycles of R-GemOx+Atezo. Patients in complete remission could then proceed to R-Atezo maintenance until progression. A safety lead-in with evaluation of dose-limiting toxicity was performed to confirm the recommended phase II dose; subsequently the treatment was administered to two expansion cohorts: one with transformed follicular lymphoma (FL) and the other with non-FL transformed DLBCL, including Richter transformation. Twenty-seven patients were enrolled. One of the six patients in the safety lead-in had a dose-limiting toxicity attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome. The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates were 59% and 33%, respectively. The overall and complete response rates in transformed FL were 79% and 43%, respectively, and 38% and 23% in transformed non-FL, respectively. The median progression-free survival and overall survival of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with relapsed/refractory transformed DLBCL.</p> Tamer Othman, Paul Frankel, Pamela Allen, Leslie L. Popplewell, Geoffrey Shouse, Tanya Siddiqi, Alexey V. Danilov, Nora Ruel, Shari Daniels, Lacolle Peters, Stella Khoo, Steven T. Rosen, Elad Sharon, Miguel Villalona-Calero, Christopher Ruel, Joseph Tuscano, Alex F. Herrera Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285185 Thu, 18 Jul 2024 00:00:00 +0000 Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth https://haematologica.org/article/view/haematol.2024.285491 <p>Multiple myeloma (MM) is a plasma cell malignancy that is considered incurable despite the recent therapeutic advances. Effective targeted therapies are, therefore, needed. Our previous studies proved that inhibiting CDK7 impairs the cell cycle and metabolic programs by disrupting E2F1 and MYC transcriptional activities, making it an appealing therapeutic target for MM. Given that CDK7 and BRD4 operate in two distinct regulatory axes in MM, we hypothesized that targeting these two complementary pathways simultaneously would lead to a deeper and more durable response. Indeed, combination therapy had superior activity against MM cell growth and viability, and induced apoptosis to a greater extent than did single-agent therapy in both cell lines and patients’ cells. This synergistic activity was also observed in Waldenström macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for the potential of combination therapy as a therapeutic strategy in MM and WM.</p> Yao Yao, Shuhui Deng, Jessica Fong Ng, Mei Yuan, Chandraditya Chakraborty, Vera JoyWeiler, Nikhil Munshi, Mariateresa Fulciniti Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285491 Thu, 25 Jul 2024 00:00:00 +0000 Risk of infections in multiple myeloma. A populationbased study on 8,672 multiple myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry https://haematologica.org/article/view/haematol.2024.285645 <p>In multiple myeloma (MM), advancements in treatments and toxicity management have enhanced survival rates. This, coupled with shifting age demographics in MM, necessitates an updated assessment of infection risks in MM patients compared to the general population. Using Swedish population-based registries, we investigated the incidence of infections in 8,672 Swedish symptomatic MM patients diagnosed 2008-2021 and 34,561 matched controls. Overall, MM patients had a 5-fold risk (hazard ratio [HR] =5.30; 95% confidence interval [CI]: 5.14-5.47) of developing a clinically significant infection compared to matched controls. Bacterial infections represented a 5-fold (HR=4.88; 95% CI: 4.70-5.07) increased risk, viral and fungal infections 7-fold compared to controls. The first year after MM diagnosis the risk of infections compared to controls was 7-fold (HR=6.95; 95% CI: 6.61-7.30) and remained elevated up to 5 years after the myeloma diagnosis. The risk of infection compared to controls remained 5-fold in MM patients with follow-up till 2022. Preceding MM diagnosis, the risk compared to matched controls was significantly increased up to 4 years before MM diagnosis (HR=1.16; 95% CI: 1.05-1.28). Among MM patients, 8% had died within 2 months of diagnosis and infection contributed to 32% of all deaths. After 1 year, 20% MM patients had died, and infection-related mortality was 27%. Our data constitute the largest population-based study to date on the risk of infections compared to the normal population in the era of modern MM therapies and confirms that infections still represent a major threat to patients and underscores importance of preventive strategies.</p> Cecilie Hveding Blimark, Kristina Carlson, Christopher Day, Sigrun Einarsdottir, Gunnar Juliusson, Moshtak Karma, Dorota Knut-Bojanowska, Gunnar Larfors, Ingemar Turesson, Mariana Villegas-Scivetti, Ingigerdur Sverrisdóttir Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285645 Thu, 18 Jul 2024 00:00:00 +0000 Rituximab maintenance after bendamustine-based treatment for follicular lymphoma and mantle cell lymphoma may exert a negative influence on SARS-CoV-2 infection outcomes https://haematologica.org/article/view/haematol.2024.285219 Ángel Serna, Víctor Navarro, Gloria Iacoboni, Laia López, Juan-Manuel Sancho, Eva González-Barca, Alberto López-García, Raúl Córdoba, Adolfo Sáez, Ana Jiménez Ubieto, Ainara Ferrero, Tomás García, Ángela Sánchez, Cristina García, Marc Bosch, Alba Cabirta, Moraima Jiménez, Ana Marín-Niebla, Francesc Bosch, Pau Abrisqueta Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285219 Thu, 11 Jul 2024 00:00:00 +0000 Respiratory syncytial virus and other vaccine-preventable infections in multiple myeloma. A population-based study on 8,672 myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry https://haematologica.org/article/view/haematol.2024.285161 Sigrun Einarsdottir, Ingigerdur Sverrisdottir, Mariana Villegas-Scivetti, Chris Day, Ingemar Turesson, Gunnar Juliusson, Markus Hansson, Gunnar Larfors, Cecilie Hveding Blimark Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285161 Thu, 27 Jun 2024 00:00:00 +0000 Safety and efficacy of human apotransferrin infusion in patients with β-thalassemia intermedia: the AIM study https://haematologica.org/article/view/haematol.2024.285045 Kadère Konté, Dorine W. Swinkels, Ilona Kleine Budde, Erfan Nur, Bart J. Biemond Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285045 Thu, 22 Aug 2024 00:00:00 +0000 Increased frequency of clonal hematopoiesis of indeterminate potential in Bloom syndrome probands and carriers https://haematologica.org/article/view/haematol.2024.285239 Isabella Lin, Angela Wei, Tsumugi A. Gebo, Paul C. Boutros, Maeve Flanagan, Nicole Kucine, Christopher Cunniff, Valerie A. Arboleda, Vivian Y. Chang Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285239 Thu, 25 Jul 2024 00:00:00 +0000 Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein https://haematologica.org/article/view/haematol.2024.285319 Navta Masand, Tracey A. Perry, Matthew Pugh, Eanna Fennell, Aoife Hennessy, Wenbin Wei, Katerina Bouchalova, David Burns, Pamela Kearns, Graham Taylor, Katerina Vrzalikova, Paul G. Murray Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285319 Thu, 22 Aug 2024 00:00:00 +0000 A novel prognostic nomogram based on imaging and molecular parameters for newly diagnosed extranodal natural killer/T-cell lymphoma patients https://haematologica.org/article/view/haematol.2024.285362 Dezhi Huang, Fu Li, Shijia Lin, Jing Xia, Bangdong Liu, Xinlei Li, Naya Ma, Yishuo Duan, Yunjing Zeng, Sha Zhou, Shuhan Tang, Wenqiu Huang, Lingyi Rao, Li Gao, Qiong Li, Xi Zhang, Jun Rao Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285362 Thu, 15 Aug 2024 00:00:00 +0000 Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials https://haematologica.org/article/view/haematol.2024.285416 Celia Gonzalez-Gil, Mireia Morgades, Thaysa Lopes, Francisco Fuster-Tormo, Pau Montesinos, Pere Barba, Marina Diaz-Beya, Lourdes Hermosin, Clara Maluquer, Jose Gonzalez-Campos, Teresa Bernal, Marta Sitges Arriaga, Lurdes Zamora, Marta Pratcorona, Rodrigo Martino, Maria Jose Larrayoz, Teresa Artola, Anna Torrent, Ferran Vall-llovera, Mar Tormo, Cristina Gil, Andres Novo, Pilar Martinez-Sanchez, Jordi Ribera, Maria-Paz Queipo, Teresa Gonzalez-Martinez, Monica Cabrero, Antonia Cladera, Jose Cervera, Alberto Orfao, Josep Maria Ribera, Eulalia Genesca Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285416 Thu, 08 Aug 2024 00:00:00 +0000 Cd39 and P2rx7-Wnt signaling enhance blast pathogenicity in an experimental model of acute myeloid leukemia https://haematologica.org/article/view/haematol.2024.285547 Lili Feng, Haohai Zhang, Changchuin Mao, Paola de Andrade Mello, Dina Stroopinsky, Eva Csizmadia, Jialin Zhou, David Avigan, Jinming Yu, Wenda Gao, Simon C. Robson Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285547 Thu, 15 Aug 2024 00:00:00 +0000 Outcomes of patients with primary central nervous system lymphoma following CD19-targeted chimeric antigen receptor T-cell therapy https://haematologica.org/article/view/haematol.2024.285613 Santiago Mercadal, Kwang Woo Ahn, Mariam Allbee-Johnson, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Sanghee Hong, Adriana Malone, Hemant Murthy, Attaphol Pawarode, Alejandro R. Sica, Melhem Solh, Celalettin Ustun, Mazyar Shadman, Craig S. Sauter, Mehdi Hamadani, Alex F. Herrera, Catherine J. Lee Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285613 Thu, 05 Sep 2024 00:00:00 +0000 Characteristics and outcomes associated with CD2 and CD25 expression on bone marrow mast cells in patients with systemic mastocytosis https://haematologica.org/article/view/haematol.2024.285740 Julien Rossignol, Sophie Georgin-Lavialle, Danielle Canioni, Omer Beganovic, Chantal Brouzes, Olivier Fain, Maël Heiblig, Clément Gourguechon, Philippe Guilpain, Cristina Bulai-Livideanu, Stéphane Barete, Julie Agopian, Fabienne Brenet, Patrice Dubreuil, Richard Lemal, Olivier Tournilhac, Louis Terriou, David Launay, Laurence Bouillet, Catharina Chatain, Ghandi Damaj, Thomas Ballul, Celine Greco, Laura Polivka, Laurent Frenzel, Cécile Meni, Hassiba Bouktit, Dina Benabou, Clotilde Devin, Caroline Gaudy-Marqueste, Marie Gousseff, Edwige Le Mouel, Antoine Neel, Dana Ranta, Roland Jaussaud, Thierry Jo Molina, Julie Bruneau, Rose-Marie Javier, Fabien Pelletier, Florence Castelain, Frederique Retornaz, Quentin Cabrera, Patricia Zunic, Marie Pierre Gourin, Ewa Wierzbicka-Hainaut, Jean François Viallard, Christian Lavigne, Cyrille Hoarau, Isabelle Durieu, Sophie Dimicoli-Salazar, Jose Miguel Torregrosa-Diaz, Audrey Duval, Nicolas Garcelon, Jeremie Lespinasse, Angèle Soria, Yannick Chantran, Michel Arock, Christine Bodemer, Olivier Lortholary, Vahid Asnafi, Olivier Hermine, Ludovic Lhermitte Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285740 Thu, 29 Aug 2024 00:00:00 +0000 Comparing the clinical trial efficacy <i>versus</i> real-world effectiveness of treatments for multiple myeloma: a population-based study https://haematologica.org/article/view/haematol.2024.285768 Alissa Visram, Kelvin Kar-Wing Chan, Hsien Seow, Gregory Pond, Anastasia Gayowsky, Ghulam Rehman Mohyuddin, Arleigh McCurdy, Irwindeep Sandhu, Christopher Venner, Guido Lancman, Amaris Balitsky, Tom Kouroukis, Robert Bruins, Shaji Kumar, Rafael Fonseca, Hira Mian Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285768 Thu, 22 Aug 2024 00:00:00 +0000 Blinatumomab is associated with better post-transplant outcome than chemotherapy in children with high-risk, first-relapse B-cell acute lymphoblastic leukemia irrespective of the conditioning regimen https://haematologica.org/article/view/haematol.2024.285837 Christina Peters, Angela Bruno, Carmelo Rizzari, Alessandra Brescianini, Arend von Stackelberg, Christin Linderkamp, Yi Zeng, Gerhard Zugmaier, Franco Locatelli Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285837 Thu, 05 Sep 2024 00:00:00 +0000 Prognostic stratification in venetoclax-based acute myeloid leukemia treatments: the molecular prognostic risk signature tested in a real-world setting https://haematologica.org/article/view/haematol.2024.285934 Gaia Ciolli, Matteo Piccini, Francesco Mannelli, Giacomo Gianfaldoni, Barbara Scappini, Laura Fasano, Francesca Crupi, Elisa Quinti, Andrea Pasquini, Jessica Caroprese, Giada Rotunno, Fabiana Pancani, Leonardo Signori, Chiara Maccari, Fiorenza I. Vanderwert, Paola Guglielmelli, Alessandro M. Vannucchi Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.285934 Thu, 05 Sep 2024 00:00:00 +0000 A phase I study of MAGE-A1-targeted T1367 T-cell receptorbased cell therapy in patients with advanced multiple myeloma https://haematologica.org/article/view/haematol.2024.286124 Josefine Krüger, Matthias Obenaus, Igor Wolfgang Blau, Dana Hoser, Martin Vaegler, Hana Rauschenbach, Ioannis Anagnostopoulos, Korinna Jöhrens, Vivian Scheuplein, Elisa Kieback, Judith Böhme, Ann-Christin von Brünneck, Jan Krönke, Antonia Busse, Gerald Willimsky, Thomas Blankenstein, Antonio Pezzutto, Ulrich Keller, Axel Nogai Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286124 Thu, 12 Sep 2024 00:00:00 +0000 Adverse prognostic impact of <i>KIT</i> exon 17 mutations despite negative flow cytometric measurable residual disease in pediatric acute myeloid leukemia with <i>RUNX1::RUNX1T1</i> https://haematologica.org/article/view/haematol.2024.286243 Shota Kato, Shin-Ichi Tsujimoto, Jun Matsubayashi, Shotaro Iwamoto, Hidefumi Hiramatsu, Yusuke Okuno, Tatsuya Kamitori, Kentaro Ohki, Takao Deguchi, Nobutaka Kiyokawa, Motohiro Kato, Junko Takita, Shiro Tanaka, Souichi Adachi, Daisuke Tomizawa, Norio Shiba Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286243 Thu, 05 Sep 2024 00:00:00 +0000 Does hemoglobin affect measures of mitochondrial respiration in red blood cells? Comment to “Increased retention of functional mitochondria in mature sickle red blood cells is associated with increased sickling tendency, hemolysis and oxidative stress” https://haematologica.org/article/view/haematol.2024.286135 Wayne T. Willis, Alexander C. Berry, L. Bruce Gladden Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286135 Thu, 01 Aug 2024 00:00:00 +0000 Oxygen release from hemoglobin has limited effects on mitochondrial respiration measured from red blood cells. Reply to the Comment on “Increased retention of functional mitochondria in mature sickle red blood cells is associated with increased sickling tendency, hemolysis and oxidative stress” https://haematologica.org/article/view/haematol.2024.286361 Antoine Stier, Sofia Esperti, Elie Nader, Damien Roussel, Philippe Connes Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/haematol.2024.286361 Thu, 15 Aug 2024 00:00:00 +0000 <i>Erratum to</i>: Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population https://haematologica.org/article/view/11884 Orna Steinberg-Shemer, Tracie A. Goldberg, Joanne Yacobovich, Carina Levin, Ariel Koren, Shoshana Revel-Vilk, Tal Ben-Ami, Amir A. Kuperman, Vered Shkalim Zemer, Amos Toren, Joseph Kapelushnik, Ayelet Ben-Barak, Hagit Miskin, Tanya Krasnov, Sharon Noy-Lotan, Orly Dgany, Hannah Tamary Copyright (c) 2025 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ https://haematologica.org/article/view/11884 Wed, 01 Jan 2025 00:00:00 +0000