HemaSphere最新文献

{"title":"Elevated serum heme oxygenase-1 in pediatric sickle cell disease: Insights from the SickleGenAfrica Network","authors":"Anna M. Sowa,&nbsp;William Kudzi,&nbsp;Vivian Paintsil,&nbsp;Amma A. Benneh-Akwasi Kuma,&nbsp;Catherine I. Segbefia,&nbsp;Edeghonghon Olayemi,&nbsp;David Nana Adjei,&nbsp;Anastasia N. K. Bruce,&nbsp;Jeffrey R. Gruen,&nbsp;Ellis Owusu-Dabo,&nbsp;Solomon Fiifi Ofori-Acquah,&nbsp;The SickleGenAfrica Network","doi":"10.1002/hem3.70209","DOIUrl":"https://doi.org/10.1002/hem3.70209","url":null,"abstract":"<p>Sickle cell disease (SCD) is characterized by chronic hemolysis, resulting in the release of extracellular heme, which contributes to oxidative stress and inflammation. Heme oxygenase-1 (HO-1), an inducible enzyme that degrades heme into cytoprotective by-products, plays a critical role in mitigating heme-induced toxicity. This study analyzed serum HO-1 levels in 2309 individuals with SCD (53% female; median age: 12 years) from the SickleGenAfrica cohort, comprising 57% hemoglobin SS disease (Hb SS), 30% hemoglobin SC disease (Hb SC), 3.1% Hb sickle beta plus thalassemia (Sβ+ thalassemia), and 9.9% Hb S-hereditary persistence of fetal hemoglobin (Hb S-HPFH). Median HO-1 levels were threefold higher in children under 16 years (69.8 ng/mL; interquartile range [IQR]: 29.8–137.6) compared to adults (23.1 ng/mL; IQR: 7.8–62.4; P &lt; 0.001), with peak levels observed in the 6–10-year age group. Across all subgroups, including sex, genotype, and hydroxyurea use, children consistently exhibited higher HO-1 levels than adults, with Hb SS patients showing the highest levels. Haptoglobin and hemopexin, key scavengers of hemoglobin and heme, respectively, were depleted in all patients, particularly in children. Overall, HO-1 levels in SCD patients were markedly elevated compared to healthy populations. These findings highlight the pronounced elevation of HO-1 in pediatric SCD patients, suggesting its potential protective role against heme-induced toxicity, especially during childhood.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients”","authors":"","doi":"10.1002/hem3.70221","DOIUrl":"https://doi.org/10.1002/hem3.70221","url":null,"abstract":"<p>Enblad AP, Krali O, Gezelius H, et al. Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients. <i>HemaSphere</i>. 2025;9(7):e70176. doi:10.1002/hem3.70176</p><p>The supplemental methods mentioned in the subsection titled “DNA methylation and RNA-sequencing data” was not included in the Supporting Information. This file has been added and cited at the applicable instance in the article.</p><p>We apologize for this error.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZRSR2 loss causes aberrant splicing in JAK2V617F-driven myeloproliferative neoplasm but is not sufficient to drive disease progression","authors":"Ranran Zhang,&nbsp;Jasmin Straube,&nbsp;Yashaswini Janardhanan,&nbsp;Rohit Haldar,&nbsp;Leanne Cooper,&nbsp;Noah Hayes,&nbsp;Charles Laurore,&nbsp;Chulwoo J. Kim,&nbsp;Marlise R. Luskin,&nbsp;Robert C. Lindsley,&nbsp;Maximilian Stahl,&nbsp;Ann Mullally,&nbsp;Anna E. Marneth,&nbsp;Megan Bywater,&nbsp;Steven W. Lane","doi":"10.1002/hem3.70225","DOIUrl":"10.1002/hem3.70225","url":null,"abstract":"&lt;p&gt;Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal disorders driven by mutations in hematopoietic stem cells (HSCs).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; &lt;i&gt;JAK2&lt;/i&gt;&lt;sup&gt;V617F&lt;/sup&gt; is the most recurrent driver mutation in MPN and results in the constitutive activation of the JAK-STAT pathway.&lt;span&gt;&lt;sup&gt;3-6&lt;/sup&gt;&lt;/span&gt; Mutations in &lt;i&gt;ZRSR2&lt;/i&gt; have been found in &lt;i&gt;JAK2&lt;/i&gt;&lt;sup&gt;V617F&lt;/sup&gt;-driven MPNs and are associated with disease progression and poor prognosis. However, the functional consequences of mutations in &lt;i&gt;ZRSR2&lt;/i&gt; in terms of disease progression in &lt;i&gt;JAK2&lt;/i&gt;&lt;sup&gt;V617F&lt;/sup&gt;-driven MPN have not been determined. In MPN, somatic mutations in &lt;i&gt;ZRSR2&lt;/i&gt; occur across the entire coding transcript, are predicted to confer a loss-of-function, and are primarily observed in male patients (Supporting Information: Figure S1).&lt;span&gt;&lt;sup&gt;7-9&lt;/sup&gt;&lt;/span&gt; Herein, using CRISPR-Cas9, we generated concomitant ZRSR2 loss in JAK2-mutated human megakaryoblastic cell lines (SET2, CHRF-288-11) and a mouse model of MPN to investigate its role in promoting disease progression. We confirmed ZRSR2 loss in both human cell lines and this mouse model by sequencing and immunoblotting (Supporting Information: Figures S2 and S3).&lt;/p&gt;&lt;p&gt;&lt;i&gt;ZRSR2&lt;/i&gt; is mainly involved in minor spliceosome assembly, with &lt;i&gt;ZRSR2&lt;/i&gt; loss previously shown to result in the mis-splicing of U12-type introns in myelodysplastic syndromes (MDSs).&lt;span&gt;&lt;sup&gt;10, 11&lt;/sup&gt;&lt;/span&gt; We therefore performed replicate multivariate analysis of transcript splicing (rMATS)&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; to detect differential intron retention between &lt;i&gt;ZRSR2&lt;/i&gt; knockout (KO) megakaryoblastic cells and controls, and identified significantly increased retained intron (RI) events false discovery rate [FDR] &lt; .05) in SET-2 &lt;i&gt;ZRSR2&lt;/i&gt; KO cell lines, but not in CHRF-288-11. However, in both megakaryoblastic cell lines, RI events tended to be more prominent in genes containing U12-type introns in the context of &lt;i&gt;ZRSR2&lt;/i&gt; loss (Figure 1A). Differential gene expression analysis was performed to assess how &lt;i&gt;ZRSR2&lt;/i&gt; loss impacts transcription. Gene set enrichment analysis (GSEA) showed enrichment for genes containing U12-type introns in both ZRSR2 KO megakaryoblastic cell lines versus control cells (Supporting Information: Figure S4A). We observed significant enrichment for megakaryocyte progenitors (MkPs) and E2F target gene sets, which are involved in MkPs and myeloid differentiation, in CHRF-288-11 &lt;i&gt;ZRSR2&lt;/i&gt; KO cells, but not in SET-2 &lt;i&gt;ZRSR2&lt;/i&gt; KO cells (Supporting Information: Figure S4B). Taken together, we conclude that &lt;i&gt;ZRSR2&lt;/i&gt; loss causes U12-type intron retention and transcriptional changes in genes containing U12-type introns in human &lt;i&gt;JAK2&lt;/i&gt;-mutant megakaryoblastic cell lines.&lt;/p&gt;&lt;p&gt;&lt;i&gt;Zrsr2&lt;/i&gt; loss in &lt;i&gt;Jak2&lt;/i&gt;&lt;sup&gt;V617F&lt;/sup&gt;-driven murine MPN was achieved by isolating bone marro","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow lymphocyte dynamics during chemotherapy in pediatric acute myeloid leukemia","authors":"Joost B. Koedijk,&nbsp;Farnaz Barneh,&nbsp;Joyce E. Meesters-Ensing,&nbsp;Marc van Tuil,&nbsp;Edwin Sonneveld,&nbsp;Sander Lambo,&nbsp;Alicia Perzolli,&nbsp;Elizabeth K. Schweighart,&nbsp;Mauricio N. Ferrao Blanco,&nbsp;Merel van der Meulen,&nbsp;Anna Deli,&nbsp;Elize Haasjes,&nbsp;Kristina Bang Christensen,&nbsp;Hester A. de Groot-Kruseman,&nbsp;Soheil Meshinchi,&nbsp;Henrik Hasle,&nbsp;Mirjam E. Belderbos,&nbsp;Maaike Luesink,&nbsp;Bianca F. Goemans,&nbsp;Stefan Nierkens,&nbsp;Jayne Hehir-Kwa,&nbsp;C. Michel Zwaan,&nbsp;Olaf Heidenreich","doi":"10.1002/hem3.70212","DOIUrl":"https://doi.org/10.1002/hem3.70212","url":null,"abstract":"<p>T-cell-directed immunotherapy, which aims to boost or induce T-cell-mediated anti-tumor immunity, has shown remarkable success in various cancers, including B-cell precursor acute lymphoblastic leukemia (BCP-ALL), making it a compelling avenue for investigation in acute myeloid leukemia (AML).<span>^{1, 2}</span> Bispecific T-cell-engagers (TCEs) are a promising form of T-cell-directed immunotherapy that redirect CD3⁺ T-cells to tumor cells, thereby inducing T-cell activation and subsequent tumor cell lysis.<span>³</span> However, bispecific TCEs, mainly targeting CD33 or CD123, have shown limited efficacy and/or high toxicity in relapsed/refractory AML.<span>^4-7</span> A proposed strategy to enhance TCE therapy in AML is their administration during periods of measurable residual disease, for example, in between chemotherapy courses, as demonstrated in BCP-ALL.<span>^{2, 8-10}</span> Chemotherapy may, however, significantly alter the immune landscape<span>¹¹</span>: anthracyclines, for example, can promote anti-tumor immunity via immunogenic cell death,<span>¹²</span> but chemotherapy may also deplete lymphocytes and induce T-cell dysfunction.<span>^{13, 14}</span> Since pre-treatment T-cell infiltration and dysfunction in the tumor microenvironment are key predictors of bispecific TCE efficacy,<span>^15-18</span> understanding how chemotherapy alters the immune landscape in the leukemic bone marrow (BM) is crucial for assessing the potential of TCEs in between chemotherapy courses in AML. Given differences in disease biology, immune system maturity, and treatment regimens between pediatric and adult AML,<span>^{19, 20}</span> pediatric-specific studies are necessary. Here, we examined the impact of chemotherapy-based regimens on the BM lymphocyte compartment in newly diagnosed pediatric AML (pAML).</p><p>We first characterized the treatment-naïve pAML BM lymphocyte compartment using diagnostic bulk RNA-sequencing (RNA-seq) data (Figure 1A). To reliably infer the lymphocyte composition from bulk RNA-seq data, we acquired a publicly-available single cell (sc) RNA-seq dataset<span>²¹</span> to generate a healthy BM cell type signature matrix for use with CIBERSORTx.<span>²²</span> To validate its performance, we retrieved BM scRNA-seq data from 27 pAML cases at diagnosis, remission, and/or relapse,<span>²³</span> and generated pseudo-bulk profiles (<i>n</i> = 62). Applying CIBERSORTx with the healthy BM reference to these pseudo-bulk profiles and comparing the deconvoluted estimates with the original scRNA-seq annotations (Figure S1A), we observed strong correlations for T-, B-, and NK-cells (T-cells: <i>r</i> = 0.72, <i>P</i> &lt; 0.001; B-cells: <i>r</i> = 0.87, <i>P</i> &lt; 0.001; NK-cells: <i>r</i> = 0.68, <i>P</i> &lt; 0.001; Figure 1B). Similarly, CD4⁺ naïve, CD8⁺ effector, and CD8<sup>+</","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of the academic anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel for the treatment of relapsed/refractory follicular lymphoma","authors":"Núria Martínez-Cibrián,&nbsp;Valentín Ortiz-Maldonado,&nbsp;Marta Español-Rego,&nbsp;Leticia Alserawan,&nbsp;Sergio Navarro,&nbsp;Nil Albiol,&nbsp;Miquel Lozano,&nbsp;Paola Charry,&nbsp;Laura Magnano,&nbsp;Andrea Rivero,&nbsp;Juan G. Correa,&nbsp;Pablo Mozas,&nbsp;Albert Cortés-Bullich,&nbsp;Carlos Jiménez-Vicente,&nbsp;Eva Giné,&nbsp;Mercedes Montoro-Lorite,&nbsp;Carla Ramos,&nbsp;Pilar Ayora,&nbsp;Hugo Calderón,&nbsp;María Sánchez-Castañón,&nbsp;Daniel Benítez-Ribas,&nbsp;Juan J. Mata-Molanes,&nbsp;Kelly Rojas,&nbsp;Xavier Setoaín,&nbsp;Sonia Rodríguez,&nbsp;Adrià Murias,&nbsp;Pau Alcubilla,&nbsp;Sara Varea,&nbsp;Eulalia Olesti,&nbsp;Mireia Bachiller,&nbsp;María Calvo-Orteu,&nbsp;Carla Sans-Pola,&nbsp;Joaquín Sáez-Peñataro,&nbsp;Carlos Fernández de Larrea,&nbsp;Armando López-Guillermo,&nbsp;E. Azucena González-Navarro,&nbsp;Manel Juan,&nbsp;Julio Delgado","doi":"10.1002/hem3.70166","DOIUrl":"https://doi.org/10.1002/hem3.70166","url":null,"abstract":"<p>We report the outcome of patients with relapsed/refractory (R/R) follicular lymphoma (FL) treated with varnimcabtagene autoleucel (var-cel), an academic anti-CD19 chimeric antigen receptor (CAR) T-cell product. Patients were included in the CART19-BE-01 clinical trial and a compassionate use program. Twenty-seven patients with FL were treated. Cytokine release syndrome (any grade) occurred in 55% of patients (4% Grade ≥3). Only 1 case (4%) of Grade 1 neurotoxicity was documented. The objective response rate was 100% at Day +100 (93% complete response rate), and the 3-year duration of response was 78%. The 3-year progression-free survival and overall survival were 78% and 81%, respectively. All patients developed B-cell aplasia, and the 3-year incidence of B-cell recovery was 17%. In conclusion, patients with R/R FL treated with var-cel obtained excellent disease control, with prolonged CAR T-cell survival and manageable toxicity. This trial was registered as NCT03144583.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of central nervous system versus systemic relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP: What should we focus on?","authors":"Magdalena Klanova,&nbsp;Samuel Hricko,&nbsp;Michal Masar,&nbsp;Prokop Vodicka,&nbsp;David Salek,&nbsp;Natasa Kopalova,&nbsp;Petra Blahovcova,&nbsp;Daniela Kuruczova,&nbsp;Katerina Benesova,&nbsp;Jozef Michalka,&nbsp;Jan Koren,&nbsp;Pavel Klener,&nbsp;Andrea Janikova,&nbsp;Marek Trneny","doi":"10.1002/hem3.70201","DOIUrl":"https://doi.org/10.1002/hem3.70201","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy in adults. Although clinical outcomes of patients with DLBCL have improved over the past two decades, a significant proportion of DLBCL patients remain at risk of lymphoma relapse/progression or death due to relapse.<span>^{1, 2}</span> Patients with high international prognostic index (IPI) or central nervous system IPI (CNS-IPI) scores face the greatest risks of systemic and CNS relapse.<span>^3-5</span> The CNS-IPI model has been validated in numerous studies and is widely used in clinical practice to guide decisions regarding CNS prophylaxis.<span>^6-8</span> However, the effectiveness of CNS prophylaxis has been repeatedly questioned in the recent retrospective studies focusing on both intrathecal (IT) and intravenous high-dose methotrexate (HD MTX).<span>^9-14</span> There is a lack of robust, prospective clinical trials evaluating the impact of CNS prophylaxis on the incidence of CNS relapse. As such, CNS prophylaxis may still be considered for high-risk patients, in accordance with international guidelines (NCCN v5.2025). However, patients classified as high-risk by IPI or CNS-IPI are at risk of not only CNS relapses but also systemic relapses. The risk proportion of these two types of relapse in the same patient population has not been formally studied to date. To address this, we analyzed the competing risks of systemic versus CNS relapse in a real-world cohort of patients with DLBCL.</p><p>Using data from the prospective observational NiHiL project (NCT03199066), we identified consecutively diagnosed adult patients with histologically confirmed DLBCL not otherwise specified or DLBCL/high-grade B-cell lymphoma (HGBL) with BCL2/MYC or BCL6 rearrangements, HGBL NOS, or T-cell/histiocyte-rich large B-cell lymphoma. Patients were diagnosed between January 2010 and December 2021 at two academic centers in the Czech Republic and were treated with anti-CD20 monoclonal antibody plus CHOP chemotherapy as first-line therapy. Patients with biopsy-proven, treatment-naïve transformed indolent lymphoma (excluding Richter's transformation) were included. Patients with CNS involvement at diagnosis were excluded. Causes of death were uniformly categorized as CNS (±systemic) relapse-related, systemic relapse-related, first-line treatment toxicity-related, other, or unknown. Deaths were considered first-line treatment toxicity-related if they occurred during first-line therapy or shortly thereafter (up to Day +60 after the last treatment administration) and were attributed to treatment toxicity in the absence of progressive or refractory disease. Deaths occurring after second or subsequent lines of therapy were considered relapse-related (CNS ± systemic or systemic), unless there was clear documentation of a non-lymphoma-related cause unrelated to active disease or its treatment (e.g., unrelated comorbidity). In such cases, the cause ","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome of patients with accelerated and blast-phase myeloproliferative neoplasms not eligible for intensive chemotherapy or allogeneic hematopoietic cell transplantation treated by azacitidine alone or in combination—A FIM study","authors":"Corentin Orvain,&nbsp;Suzanne Tavitian,&nbsp;Clémence Mediavilla,&nbsp;Françoise Boyer,&nbsp;Alberto Santagostino,&nbsp;Geoffroy Venton,&nbsp;Samia Madene,&nbsp;Tony Marchand,&nbsp;Pascal Turlure,&nbsp;Diane Lara,&nbsp;Lenaig Le Clech,&nbsp;Katell Le Du,&nbsp;Jean-Baptiste Robin,&nbsp;Lise Willems,&nbsp;Anaïse Blouet,&nbsp;Thomas Systchenko,&nbsp;Mathieu Wemeau,&nbsp;Hélène Pasquer,&nbsp;Mélanie Mercier,&nbsp;Christophe Nicol,&nbsp;Laurence Legros,&nbsp;Antoine Machet,&nbsp;Franck-Emmanuel Nicolini,&nbsp;Lydia Roy,&nbsp;Clémentine Salvado,&nbsp;Guillaume Denis,&nbsp;Elsa Lestang,&nbsp;Kamel Laribi,&nbsp;Damien Luque Paz,&nbsp;Jean-Jacques Kiladjian,&nbsp;Eric Lippert,&nbsp;Lina Benajiba,&nbsp;Jean-Christophe Ianotto","doi":"10.1002/hem3.70202","DOIUrl":"https://doi.org/10.1002/hem3.70202","url":null,"abstract":"<p>Accelerated-phase (AP) or blast-phase (BP) myeloproliferative neoplasms (MPNs) are associated with dismal prognosis, with non-curative therapies such as hypomethylating agents (HMAs) considered in patients not eligible for intensive therapy, while some studies advocate for combination therapy with either ruxolitinib (RUXO) or venetoclax (VEN). To assess the relationship between treatment modalities and outcome, herein, we report a multicentric cohort of 149 patients (median age, 75 years) with AP/BP MPN not eligible for intensive therapy and/or allogeneic hematopoietic cell transplantation who received azacitidine (AZA) alone (<i>n</i> = 60) or in combination (<i>n</i> = 89; VEN [<i>n</i> = 51], RUXO [<i>n</i> = 27], or both [<i>n</i> = 9], isocitrate dehydrogenase inhibitors [<i>n</i> = 2]) between January 2019 and October 2023. With a median follow-up of 15 months, the median overall survival of the full cohort was 8.04 months, with a 3-year overall survival (OS) of 13%. Among disease characteristics, OS was lower in patients with BP (6.24 vs. 18.00 months in patients with AP disease, P = 0.03), complex karyotype (6.00 vs. 13.08 months, P = 0.005), and <i>TP53</i> mutations (8.04 vs. 11.04 months, P = 0.009). OS was nonsignificantly higher in patients receiving AZA combinations (10.08 vs. 6.96 months in patients receiving AZA monotherapy, P = 0.12). When analyzing AZA combinations separately, patients who were treated with AZA–RUXO had higher OS (18.00 vs. 9.00 vs. 10.08 months in patients receiving AZA–VEN and AZA–VEN–RUXO, P = 0.015). The improved survival with AZA–RUXO in the absence of complex karyotype and/or <i>TP53</i> mutations warrants further prospective validation. New therapeutic options are urgently needed, especially in patients with complex karyotype and/or <i>TP53</i> mutations.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Results in pediatric T-ALL patients treated in trial AIEOP-BFM ALL 2009: Prognostic factors in the context of modern risk-adapted therapy","authors":"Gunnar Cario,&nbsp;Maria Grazia Valsecchi,&nbsp;Valentino Conter,&nbsp;Giacomo Gotti,&nbsp;Anja Möricke,&nbsp;Martin Stanulla,&nbsp;Michaela Vossen-Gajcy,&nbsp;Lennart Lenk,&nbsp;Jan Stary,&nbsp;Ondrej Hrusak,&nbsp;Michael Dworzak,&nbsp;Andishe Attarbaschi,&nbsp;Draga Barbaric,&nbsp;Franco Locatelli,&nbsp;Nicole Bodmer,&nbsp;Sarah Elitzur,&nbsp;Daniela Silvestri,&nbsp;Luciano Dalla-Pozza,&nbsp;Franca Fagioli,&nbsp;Andreas E. Kulozik,&nbsp;Shai Izraeli,&nbsp;Carmelo Rizzari,&nbsp;Annika Rademacher,&nbsp;Barbara Buldini,&nbsp;Jean-Pierre Bourquin,&nbsp;Martin Zimmermann,&nbsp;Martin Schrappe,&nbsp;Andrea Biondi","doi":"10.1002/hem3.70206","DOIUrl":"https://doi.org/10.1002/hem3.70206","url":null,"abstract":"<p>To improve the outcome of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients, the AIEOP-BFM ALL 2009 trial modified T-ALL stratification and treatment based on AIEOP-BFM ALL 2000 and other pediatric ALL groups' results. This report aims to describe the outcome of T-ALL patients in trial AIEOP-BFM ALL 2009 and evaluate prognostic features defined within the end of induction (EOI) therapy, for future protocols stratification and interventions. From 06/2010 to 02/2017, 872 T-ALL patients, aged 1–17, were enrolled. High risk (HR) criteria were prednisone poor response (PPR), Day 15 flow cytometry minimal residual disease (MRD) ≥ 10%, no complete remission at EOI, or polymerase chain reaction (PCR)-MRD ≥ 5 × 10⁻⁴ at end of consolidation (EOC). Three Cox regression models on event-free survival (EFS) evaluated prognostic factors. Overall, 5-year EFS and survival were 79.9% ± 1.4% and 84.9% ± 1.2% with cumulative incidence of relapse (CIR) and death of 13.0% ± 1.2% and 5.9% ± 0.8%. Five-year EFS and CIR were 86.8% ± 1.6% and 8.7% ± 1.3% in non-HR patients (<i>n</i> = 470); 71.9% ± 2.3% and 18.0% ± 1.9% in HR patients (<i>n</i> = 402). High PCR-MRD levels at EOI and EOC were prognostic in all models, with EOC-MRD ≥ 5 × 10⁻³ related to a hazard ratio of 6.22 (P &lt; 0.001). When a model considered factors identified at EOI only, central nervous system (CNS)3 (hazard ratio = 2.3, P &lt; 0.001), PPR (hazard ratio = 1.74, P = 0.02), and high EOI-MRD (hazard ratio 4.71 for ≥5 × 10⁻² vs. negative, P &lt; 0.001) significantly impacted EFS. Results of T-ALL patients in AIEOP-BFM ALL 2009 were favorable. While EOC-MRD remained the strongest prognostic predictor, PPR, CNS3 disease, and EOI-MRD showed relevant prognostic value, with CNS3 and EOI-MRD ≥ 5 × 10⁻² being candidate criteria for early stratification and intervention modifications.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 9","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention and treatment of venous thromboembolism in patients with multiple myeloma: Clinical practice guidelines on behalf of the European Myeloma Network","authors":"Grigoris Gerotziafas,&nbsp;Despina Fotiou,&nbsp;Inger Nijhof,&nbsp;Cihan Ay,&nbsp;Ramon Lecumberri,&nbsp;Alessandra Laroca,&nbsp;Gordon Cook,&nbsp;Monika Engelhardt,&nbsp;Sonja Zweegman,&nbsp;Michel Delforge,&nbsp;Anthony Maraveyas,&nbsp;Eleftheria Lefkou,&nbsp;Marina Marchetti,&nbsp;Niels W. C. J. Van de Donk,&nbsp;Francesca Gay,&nbsp;Heinz Ludwig,&nbsp;Hermann Einsele,&nbsp;Jesus F. San Miguel,&nbsp;Meletios A. Dimopoulos,&nbsp;Mario Boccadoro,&nbsp;Pieter Sonneveld,&nbsp;Anna Falanga,&nbsp;Evangelos Terpos","doi":"10.1002/hem3.70177","DOIUrl":"https://doi.org/10.1002/hem3.70177","url":null,"abstract":"<p>Venous thromboembolism (VTE) is a frequent complication in patients with multiple myeloma (MM) that leads to increased morbidity, mortality, treatment interruptions, and reduced quality of life. Αn Expert Panel Consensus Guideline on behalf of the European Myeloma Network provides evidence-based recommendations for VTE prevention and treatment in patients with MM. Key recommendations include the following:\u0000\u0000 </p><p>By implementing these guidelines, healthcare providers can improve the prevention and treatment of VTE in patients with MM, leading to better clinical outcomes and quality of life.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 8","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary evidence of CAR T-cell therapy activity in vitreoretinal lymphomas: An LOC network study","authors":"Cécile Pivert,&nbsp;Adélaïde Toutée,&nbsp;Christophe Parizot,&nbsp;Denis Malaise,&nbsp;Alexandre Matet,&nbsp;Valérie Touitou,&nbsp;Magali Le Garff-Tavernier,&nbsp;Damien Roos-Weil,&nbsp;Sarah Touhami,&nbsp;Nabih Azar,&nbsp;Ines Boussen,&nbsp;Véronique Morel,&nbsp;Madalina Uzunov,&nbsp;Clotilde Bravetti,&nbsp;Carole Metz,&nbsp;Eve Todesco,&nbsp;Delphine Sterlin,&nbsp;Carole Soussain,&nbsp;Kahina Ouis Tarhi,&nbsp;Anne Besançon,&nbsp;Khê Hoang-Xuan,&nbsp;Sylvain Choquet,&nbsp;Caroline Houillier,&nbsp;Marine Baron","doi":"10.1002/hem3.70208","DOIUrl":"https://doi.org/10.1002/hem3.70208","url":null,"abstract":"&lt;p&gt;Vitreoretinal lymphoma (VRL) is a rare subtype of large B-cell lymphoma (LBCL) that may present as an isolated condition or with central nervous system (CNS) or systemic involvement. Like the brain, the eye is an immune-privileged site, posing unique therapeutic challenges according to the blood–eye barrier. Despite its typically indolent course, VRL is difficult to eradicate, and the long-term prognosis is poor because of the high risk of CNS involvement.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The median overall survival (OS) is 36–75 months for primary VRL and approximately 57 months for isolated vitreoretinal relapses of primary CNS lymphomas.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Therefore, new therapeutic strategies are urgently needed.&lt;/p&gt;&lt;p&gt;Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advancement in managing systemic LBCL.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; Studies show that CAR T-cells can cross the blood–brain barrier and demonstrate high efficacy in CNS lymphomas,&lt;span&gt;&lt;sup&gt;5-8&lt;/sup&gt;&lt;/span&gt; but their potential in VRL treatment is not fully understood, and their efficiency has never been described from an ophthalmologic point of view with the newest validated exams.&lt;/p&gt;&lt;p&gt;Since 2020, CAR T-cell therapy has been considered within the French oculocerebral lymphoma network (LOC network) for relapsed or refractory VRL. This study retrospectively analyzed patients with primary or secondary VRL treated with CAR T-cells.&lt;/p&gt;&lt;p&gt;We retrospectively identified all VRL patients treated with commercial anti-CD19 CAR T-cells at Pitié-Salpêtrière Hospital (Paris) via the LOC network database until November 2023. Eligible patients had active vitreoretinal involvement, either isolated or with CNS involvement. VRL could be primary or secondary to systemic or CNS lymphoma. Data were retrospectively collected from medical records between April and October 2024. The LOC database was approved by the Institutional Ethical Committee of the coordinating center and the French “Commission Nationale de l'Informatique et des Libertés” (CNIL). All patients provided written informed consent. Responses were evaluated using International Primary CNS Lymphoma Collaborative Group (IPCG) criteria,&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; and all ophthalmologic examinations of the patient performed immediately before and after the CAR T-cells were systematically reviewed by a single ophthalmologist from the Pitié-Salpétrière Hospital, based on the photographs taken at each consultation (Supplementary Methods). Progression-free survival (PFS), ophthalmic-free survival (OFS), and OS were defined as the time from CAR T-cell infusion: “to CNS, ophthalmic or systemic disease progression or relapse/to ophthalmic progression or relapse/and to death respectively.” Survival rates were calculated using the Kaplan–Meier method. Statistical analyses were conducted using GraphPad Prism v10.0. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per 2019 Ameri","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 8","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}