American Journal of Hematology最新文献

{"title":"The 2024 Three-Strata Baseline Anemia Definition of the Revised IWG-ELN Criteria Dissects Survival in Ruxolitinib-Treated Myelofibrosis Patients","authors":"Margherita Maffioli, Barbara Mora, Alessandra Iurlo, Elena Maria Elli, Maria Chiara Finazzi, Mirko Farina, Elisa Rumi, Marianna Caramella, Maria Cristina Carraro, Mariella D'Adda, Alfredo Molteni, Elda Mimiola, Francesca Lunghi, Alessandro Vismara, Marta Ubezio, Maria Chiara Di Chio, Michela Anghilieri, Daniele Cattaneo, Matteo Giovanni Della Porta, Lorenza Bertù, Marta Coscia, Francesco Passamonti","doi":"10.1002/ajh.27734","DOIUrl":"10.1002/ajh.27734","url":null,"abstract":"<p>Baseline anemia is a known negative prognostic feature in myelofibrosis (MF), possibly contrary to ruxolitinib (RUX)-induced anemia. On the other hand, transfusion dependence (TD) has a detrimental impact that is irrespective of treatment status. The lack of consistency among definitions of TD and anemia response in MF has, however, partially hampered trial result interpretation and inter-study comparisons. In August 2024, <i>Blood</i> has released the Revised International Working Group-European LeukemiaNet (IWG-ELN) criteria for anemia response in MF, redefining both baseline anemia and its response to treatment. The criteria have been formulated by an international group of experts on the basis of available data in MF, adopting some myelodysplastic syndromes-specific features [<span>1</span>]. Inherent to their nature, not all aspects of the revised criteria, especially with respect to the number of transfusions necessary to define TD anemia (TDA) and the fine-grained characterization of anemia response, have been formally tested for their prognostic value.</p><p>We thus set out to apply the updated criteria within the ambispective observational RUXOREL-MF study (NCT03959371) to establish the impact on survival of the new definition of TDA and non-TDA and, second, to assess early anemia response in RUX-treated MF patients. The RUXOREL-MF study focuses on RUX-treated MF patients within an extensive hematology network, as already described [<span>2</span>]. The study was approved by the Review Board of each institution and conducted in accordance with the Declaration of Helsinki. The study database comprises 288 patients regularly followed at 17 centers. In-depth information regarding the number of transfused units and corresponding dates is available, in order to correctly apply the revised IWG-ELN criteria. Given the prognostic relevance of early modifications of transfusion status under RUX [<span>2</span>], we decided to focus the anemia response part of the analysis on the first 6 months of treatment. Patient selection criteria for enrollment in our analysis were as previously defined [<span>2</span>], resulting in a cohort of 209 patients. Four patients, however, lacked baseline transfusion status and were excluded.</p><p>The revised IWG-ELN criteria proposed three strata for anemia definition, and we applied them to the RUXOREL-MF cohort. A hemoglobin (Hgb) level of < 10 g/dL, irrespective of gender, is considered a suitable key inclusion criterion for clinical trials targeting anemia in MF. TDA is defined as the need for ≥ 3 units of red blood cells/12 weeks. Non-TDA includes anemic subjects who do not qualify for TDA.</p><p>Responses are graded into “major” and “minor” and are separate for TDA and non-TDA. Major responses require the absence of transfusions for 12 weeks and a rolling 12-week average Hgb increase of ≥ 1.5 g/dL from pretreatment baseline. Minor responses comprise a ≥ 50% reduction in transfusions in TDA and a rollin","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 9","pages":"1656-1659"},"PeriodicalIF":9.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Chronic Myeloid Leukemia Patients Not in Deep Molecular Response: Results From the GIMEMA LabNet CML Network Database","authors":"Fabio Stagno, Rosalba Cucci, Giovanni Marsili, Fausto Castagnetti, Sara Galimberti, Barbara Izzo, Federica Sorà, Simona Soverini, Monica Messina, Alfonso Piciocchi, Massimiliano Bonifacio, Daniela Cilloni, Alessandra Iurlo, Giovanni Martinelli, Gianantonio Rosti, Paola Fazi, Marco Vignetti, Massimo Breccia, Alessandro Allegra, Fabrizio Pane","doi":"10.1002/ajh.27733","DOIUrl":"10.1002/ajh.27733","url":null,"abstract":"<p>Chronic myeloid leukemia (CML) is currently managed as a chronic disease requiring long-term treatment and a close molecular monitoring in many patients [<span>1</span>]. Evidence suggests that in a substantial number of patients who achieved a stable sustained deep molecular response (DMR) the treatment with tyrosine kinase inhibitors (TKIs) can be safely discontinued [<span>2, 3</span>]. Hence, treatment-free remission (TFR) is a strategy increasingly considered as a feasible treatment goal in about 20%–40% of CML patients [<span>4</span>]. Nevertheless, a proportion of patients with CML in chronic-phase (CP) treated with TKIs still remain in stable major molecular remission (MR3) or less (MR2 only) without achieving a DMR, therefore requiring long-term TKIs therapy [<span>5</span>] as well as a long-term molecular monitoring [<span>6</span>].</p><p>The Italian Group for Adult Hematological Malignancies (GIMEMA) activated in 2008 a project named GIMEMA LabNet CML network with the aim of reassuring a nationwide fast and harmonized molecular diagnostic and monitoring process to all CML patients. The network is now made up of 51 standardized laboratories for clinical and research purposes linked with 144 hematological centers. The connection between the hematology centers and laboratories is managed by a web-based general data protection regulation (GDPR) compliant platform. LabNet digital infrastructure manages the traffic of molecular diagnostic tests between clinical centers and laboratories with the aim of providing a standardized evaluation of minimal residual disease. Therefore, if not all, most of the CML patients living in Italy are monitored for their disease at the same level of accuracy and harmonization.</p><p>The aim of our analysis was to describe, in the pure real-life scenario of the GIMEMA LabNet CML network, the long-term outcome of those CML patients in stable MR3/MR2. The LabNet CML database represented the data source of our analysis. To participate in the network, laboratories fulfilled quality controls and regularly participated in quality control rounds.</p><p>At the time of the current analysis, the LabNet database contained data of 9699 patients affected by CML with evaluable samples for <i>BCR::ABL1</i> transcripts. All patients gave written informed consent. We selected the patient cohort by analyzing all those with CP-CML treated frontline with Imatinib (IM), Dasatinib (DAS), or Nilotinib (NIL) at conventional doses who achieved, within 6 months, an MR3 or less (MR2) and showed evaluable samples for molecular response at least 24 months from the first MR3 or MR2 achievement. We collected only <i>BCR::ABL1</i> kinetic and molecular data according to clinical practice. The LabNet CML Network adopted Subjective Objective Assessment and Plan (SOAP) notes according to the European LeukemiaNet guidelines [<span>6</span>]. The <i>BCR::ABL1</i> transcript levels were measured in each laboratory from peripheral blood samples","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1467-1470"},"PeriodicalIF":10.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Impact of Graft Cryopreservation on Allogeneic Stem Cell Transplantation: An Italian, Registry-Based Study on Behalf of the “Gruppo Italiano Per Il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare” (GITMO)","authors":"Irene Defrancesco,&nbsp;Virginia Valeria Ferretti,&nbsp;Patrizia Chiusolo,&nbsp;Domenico Russo,&nbsp;Chiara Nozzoli,&nbsp;Attilio Olivieri,&nbsp;Massimiliano Gambella,&nbsp;Irene Maria Cavattoni,&nbsp;Stefania Bramanti,&nbsp;Stella Santarone,&nbsp;Renato Fanin,&nbsp;Roberto Cairoli,&nbsp;Simona Piemontese,&nbsp;Matteo Parma,&nbsp;Francesco Onida,&nbsp;Alessandro Busca,&nbsp;Luca Castagna,&nbsp;Angela Cuoghi,&nbsp;Domenico Pastore,&nbsp;Nicola Mordini,&nbsp;Fabio Benedetti,&nbsp;Cristina Skert,&nbsp;Carlo Borghero,&nbsp;Anna Paola Iori,&nbsp;Franca Fagioli,&nbsp;Vincenzo Pavone,&nbsp;Carmine Selleri,&nbsp;Simone Cesaro,&nbsp;Maurizio Musso,&nbsp;Marco Ladetto,&nbsp;Daniele Vallisa,&nbsp;Paola Carluccio,&nbsp;Alessandra Picardi,&nbsp;Monica Tozzi,&nbsp;Alessandra Biffi,&nbsp;Giuseppe Milone,&nbsp;Maura Faraci,&nbsp;Arcangelo Prete,&nbsp;Lucia Prezioso,&nbsp;Antonio Maria Risitano,&nbsp;Francesco Paolo Tambaro,&nbsp;Veronica Tintori,&nbsp;Piero Galieni,&nbsp;Fabrizio Pane,&nbsp;Caterina Zerbi,&nbsp;Antonio Bianchessi,&nbsp;Giulia Losi,&nbsp;Francesco Romano,&nbsp;Alessia Taurino,&nbsp;Elena Oldani,&nbsp;Nicola Polverelli,&nbsp;Francesca Bonifazi,&nbsp;Massimo Martino","doi":"10.1002/ajh.27731","DOIUrl":"10.1002/ajh.27731","url":null,"abstract":"<p>The coronavirus disease 2019 (COVID-19) pandemic created major challenges for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Scientific societies and authorities recommended cryopreserving grafts before starting conditioning regimens, despite limited data on the clinical impact. The Italian Group for Bone Marrow Transplantation (GITMO) conducted a registry-based study involving 3492 patients who underwent allo-HSCT between March 2018 and September 2021. The cryopreserved cohort (<i>n</i> = 976) included patients who received cryopreserved grafts during the pandemic and was compared to the historical cohort (<i>n</i> = 2516). Graft cryopreservation was associated with a lower day 30 incidence of neutrophil and platelet engraftment (adjusted sHR = 0.8 and 0.7, <i>p</i> = 0.031 and <i>p</i> &lt; 0.001, respectively) and delayed hematopoietic recovery. However, primary graft failure rates at day +30 were similar in the cryo and historical cohort (4% vs. 5%, respectively; <i>p</i> = 0.337), also after adjustment (RR = 1.19, <i>p</i> = 0.518). Day 100 incidence of grade II-IV acute GVHD was comparable between the two groups (adjusted sHR = 1.2, <i>p</i> = 0.194). Regarding chronic GVHD incidence, we found that it was higher in patients aged &lt; 18 years in the cryo group (adjusted sHR = 3.9, <i>p</i> = 0.002), but lower in those aged 18–55 years (adjusted sHR = 0.7, <i>p</i> = 0.008). Cumulative incidence of relapse did not differ between historical and cryo cohort (adjusted sHR 1.0. <i>p</i> = 0.943), as well as non-relapse mortality (adjusted sHR 1.1, <i>p</i> = 0.196) and relapse-free survival (adjusted sHR = 1.1, <i>p</i> = 0.197). However, a shorter overall survival was observed in the cryopreserved group (adjusted HR = 1.2, <i>p</i> = 0.038). Transplant centers should carefully balance the benefits and drawbacks of cryopreservation in allo-HSCT.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1354-1364"},"PeriodicalIF":10.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenging the Adverse Label: Diverse Outcomes of ELN 2022 Adverse Cytogenetic Subgroups in Acute Myeloid Leukemia Patients Allografted in First Remission: From EBMT ALWP","authors":"Ali Bazarbachi,&nbsp;Jacques-Emmanuel Galimard,&nbsp;Iman Abou Dalle,&nbsp;Gérard Socié,&nbsp;Jurjen Versluis,&nbsp;Depei Wu,&nbsp;Matthias Eder,&nbsp;Hélène Labussière-Wallet,&nbsp;Ibrahim Yakoub-Agha,&nbsp;Johan Maertens,&nbsp;Edouard Forcade,&nbsp;Tobias Gedde-Dahl,&nbsp;Goda Choi,&nbsp;Cristina Castilla-Llorente,&nbsp;Frederic Baron,&nbsp;Eolia Brissot,&nbsp;Jordi Esteve,&nbsp;Arnon Nagler,&nbsp;Mohamad Mohty,&nbsp;Fabio Ciceri","doi":"10.1002/ajh.27726","DOIUrl":"10.1002/ajh.27726","url":null,"abstract":"<div>\u0000 \u0000 <p>According to the European LeukemiaNet (ELN) 2022 classification, acute myeloid leukemia (AML) patients with intermediate or adverse risk are offered allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission. In this EBMT study, we included 1735 adult AML patients with ELN-2022 adverse-risk cytogenetics allografted between 2010 and 2022 in first remission (67% de novo AML, median age 56 years). Eleven non-overlapping adverse-risk cytogenetics groups were defined. The five most frequent were: Group 1 [<i>n</i> = 394; monosomy 17 or abn(17p); 2-year leukemia-free survival (LFS) 22%, and overall survival (OS) 25%]; Group 2 [<i>n</i> = 313; complex karyotype (CK) involving monosomy 5, monosomy 7, or del(5q) without monosomy 17 or abn(17p); LFS 27%, OS 37%]; Group 3 [<i>n</i> = 201; monosomy 5, monosomy 7, or del(5q) without CK and without monosomy 17 or abn(17p); LFS: 55%, OS: 63%]; Group 4 [<i>n</i> = 256; CK without monosomal karyotype (MK) or adverse additional cytogenetic abnormalities (ACA); LFS 50%, OS 61%]; Group 5 [<i>n</i> = 213; t(v, 11q23) without adverse ACA; LFS 50%, OS 59%]. In multivariable analysis, compared to CK without adverse ACA, LFS was negatively affected by monosomy 17 or 17p abnormalities, monosomy 5, 7, or del(5q) in the presence of CK, and t(8;16). In conclusion, this study revealed a very poor outcome of allografted AML patients with monosomy 17 or 17p abnormalities or CK involving monosomy 5, monosomy 7, and del5q. Outcomes were relatively favorable for most other ELN 2022 adverse categories, including CK with or without MK other than 5, 7, and 17, indicating that allo-HSCT can overcome their poor outcome.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1374-1386"},"PeriodicalIF":10.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176952","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":"Identification of a CAR-Derived Clone by NGS-Based MRD After Fully Human BCMA CAR T-Cell Therapy in Multiple Myeloma","authors":"Wenqiang Yan,&nbsp;Jiao Chang,&nbsp;Chenxing Du,&nbsp;Yuntong Liu,&nbsp;Rui Lv,&nbsp;Hesong Zou,&nbsp;Tengteng Yu,&nbsp;Shuaishuai Zhang,&nbsp;Tingyu Wang,&nbsp;Weiwei Sui,&nbsp;Shuhui Deng,&nbsp;Yan Xu,&nbsp;Wenyang Huang,&nbsp;Shuhua Yi,&nbsp;Dehui Zou,&nbsp;Jianxiang Wang,&nbsp;Lugui Qiu,&nbsp;Yujiao Jia,&nbsp;Gang An","doi":"10.1002/ajh.27732","DOIUrl":"10.1002/ajh.27732","url":null,"abstract":"&lt;p&gt;B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy has significantly improved survival outcomes in patients with relapsed or refractory multiple myeloma (RRMM), achieving unprecedented depth of response compared to conventional salvage regimens [&lt;span&gt;1-3&lt;/span&gt;]. Minimal residual disease (MRD) negativity has emerged as a strong predictor of favorable prognosis in this setting [&lt;span&gt;4&lt;/span&gt;] and is increasingly recognized as a surrogate endpoint for accelerated drug approvals of novel agents.&lt;/p&gt;&lt;p&gt;Next-generation flow cytometry (NGF) and next-generation sequencing (NGS)-based MRD assessments are the most widely adopted approaches, offering sensitivities of approximately 10&lt;sup&gt;−5&lt;/sup&gt; and 10&lt;sup&gt;−6&lt;/sup&gt;, respectively. In addition to their high sensitivity, NGS-MRD enables longitudinal tracking of clonal dynamics and the identification of potential subclonal evolution. However, the interpretation of NGS-MRD in the context of genetically engineered T cell products remains limited and poorly characterized.&lt;/p&gt;&lt;p&gt;In our center, most patients attained NGS-MRD negativity following BCMA CAR-T infusion in real-world clinical settings. Unexpectedly, in a subset of these patients, we identified a persistent novel clone sequence that was not related to the original tumor clone post-infusion. This novel clone gradually declined over time but remained detectable in serial MRD assessments. Whether this uncommon finding reflects clonal evolution, tumor relapse, secondary neoplasm, or a previously unrecognized signal derived from the CAR-T product itself remains to be determined. To investigate this phenomenon, we conducted a retrospective study utilizing a multi-modal approach to characterize the origin and clinical relevance of this novel clone.&lt;/p&gt;&lt;p&gt;We retrospectively analyzed 55 myeloma patients who received BCMA CAR-T cell therapy at our center and had at least one NGS-MRD assessment post-infusion, as part of real-world observational studies or investigator-initiated trials (IIT). Written informed consent was obtained from all patients, and the study was approved by the Ethics Committee of the Blood Diseases Hospital.&lt;/p&gt;&lt;p&gt;Fluorescence in situ hybridization (FISH) and NGF-based MRD were performed as previously described [&lt;span&gt;5&lt;/span&gt;]. NGS-MRD analysis was conducted using the Neo-MRD assay (Neoimmune, Shenzhen, China), targeting V(D)J rearrangements in IGH, IGK, and IGL genes. A two-step PCR was applied: a 28-cycle multiplex PCR to amplify V and J segments, followed by a 12-cycle universal PCR to add Illumina adaptors. Libraries were sequenced on the NovaSeq 6000 platform (paired-end, 150 bp). CDR3 sequences with fewer than three reads per million were excluded. Dominant clones were defined based on &gt; 3% clonal frequency and &gt; 0.2% nucleated cell content and were tracked across timepoints.&lt;/p&gt;&lt;p&gt;Lentiviral vector copy number (VCN) was quantified using digital droplet PCR (ddPCR) in 27 bone marrow (BM) DNA sampl","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 9","pages":"1660-1664"},"PeriodicalIF":9.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Benefit of Early Daratumumab Use in Multiple Myeloma is Undefined","authors":"Ruben Van Dijck,&nbsp;Zoran Erjavec,&nbsp;John-John B. Schnog","doi":"10.1002/ajh.27728","DOIUrl":"10.1002/ajh.27728","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1277-1282"},"PeriodicalIF":10.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172198","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":"CPX-351 (Vyxeos) in Acute Myeloid Leukemia: Time to Move on?","authors":"Naseema Gangat,&nbsp;Ayalew Tefferi","doi":"10.1002/ajh.27730","DOIUrl":"10.1002/ajh.27730","url":null,"abstract":"<p>CPX-351 has similar efficacy but more toxicity compared to venetoclax+hypomethylating agent therapy.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1271-1276"},"PeriodicalIF":10.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165663","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":"Impact of Conditioning Intensity on Clinical Outcomes of Second Allogeneic Hematopoietic Cell Transplantation for Relapse After First Transplantation","authors":"Kazuki Yoshimura,&nbsp;Hideki Nakasone,&nbsp;Masaharu Tamaki,&nbsp;Hiroki Hosoi,&nbsp;Kazuaki Kameda,&nbsp;Naoyuki Uchida,&nbsp;Noriko Doki,&nbsp;Takahiro Fukuda,&nbsp;Satoshi Yoshihara,&nbsp;Yasuo Mori,&nbsp;Hirohisa Nakamae,&nbsp;Masatsugu Tanaka,&nbsp;Yuta Katayama,&nbsp;Tetsuya Eto,&nbsp;Yuta Hasegawa,&nbsp;Shuichi Ota,&nbsp;Satoshi Takahashi,&nbsp;Makoto Yoshimitsu,&nbsp;Fumihiko Ishimaru,&nbsp;Junya Kanda,&nbsp;Yoshiko Atsuta,&nbsp;Kimikazu Yakushijin","doi":"10.1002/ajh.27709","DOIUrl":"10.1002/ajh.27709","url":null,"abstract":"<div>\u0000 \u0000 <p>Although second allogeneic hematopoietic cell transplantation HCT (HCT2) is a potentially curative treatment for patients relapsing after their first HCT (HCT1), it is associated with higher non-relapse mortality (NRM) compared with HCT1. Furthermore, while reduced-intensity conditioning (RIC) in HCT2 might decrease NRM, there is no consensus on which patients may benefit from RIC. We retrospectively analyzed 2478 patients who underwent HCT2 for relapse of hematologic malignancies after HCT1. In a multivariate analysis, older recipient age, short duration between HCT1 and HCT2, RIC in HCT1, HCT-CI ≥ 2, and ECOG PS ≥ 2 were associated with an increased risk of NRM. RIC in HCT2 was associated with better NRM compared to myeloablative conditioning (MAC) (hazard ratio [HR] 0.83, 95% confidence interval [CI]: 0.72–0.97; <i>p</i> = 0.018), but was not significantly associated with overall survival (OS) (HR 0.91, 95% CI: 0.82–1.01; <i>p</i> = 0.075). We observed a significant interaction for NRM between extensive cGVHD in HCT1 and the conditioning intensity of HCT2 (interaction <i>p</i> &lt; 0.001), meaning that the benefit of RIC in HCT2 was seen in patients with extensive cGVHD in HCT1, but not in those without cGVHD. RIC in HCT2 was also associated with superior OS in patients with extensive cGVHD in HCT1 (HR 0.68, 95% CI: 0.49–0.93; <i>p</i> = 0.02), with significant interaction between the conditioning intensity and the prior history of extensive cGVHD (interaction <i>p</i> = 0.01). This study suggests that RIC in HCT2 reduces NRM for HCT2 and improves OS, especially in patients with a history of extensive cGVHD.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1185-1195"},"PeriodicalIF":10.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122226","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":"A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia","authors":"Tapan M. Kadia,&nbsp;Wei-Ying Jen,&nbsp;Alex Bataller,&nbsp;Alexandre Bazinet,&nbsp;Gautam Borthakur,&nbsp;Elias Jabbour,&nbsp;Wei Qiao,&nbsp;Nicholas J. Short,&nbsp;Koichi Takahashi,&nbsp;Ghayas C. Issa,&nbsp;Courtney D. DiNardo,&nbsp;Guillermo Montalban-Bravo,&nbsp;Naveen Pemmaraju,&nbsp;Andrew Tran,&nbsp;Vanthana Bharathi,&nbsp;Sanam Loghavi,&nbsp;Amin M. Alousi,&nbsp;Uday Popat,&nbsp;Naval G. Daver,&nbsp;Farhad Ravandi,&nbsp;Hagop M. Kantarjian","doi":"10.1002/ajh.27723","DOIUrl":"10.1002/ajh.27723","url":null,"abstract":"<div>\u0000 \u0000 <p>Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 (CPX-351 dosed at daunorubicin 44 mg/m² on days 1,3, and 5 and venetoclax 300 mg days 2–8) being chosen as the RP2D. Thirty three patients with a median age of 58 years (range, 26–72) were treated. Patients were heavily pretreated, with 58% with prior venetoclax exposure, 44% in the second salvage or later, and 30% with prior stem cell transplant (SCT). Adverse cytogenetics were present in 51% of patients, with myelodysplasia-related mutations in 64%, and <i>TP53</i>^mut in 21%. The overall response rate (ORR) was 46% (95% CI, 30–62), with a composite CR rate (CRc) of 39% (95% CI, 25–56). Patients in first salvage with wildtype <i>TP53</i> had a CRc rate of 70% (95% CI, 40–89), with undetectable MRD in 71% (95% CI, 36–92) and a 2-year OS of 49% (95% CI, 23–100). Eleven (73%) responding patients underwent SCT. The 30-day mortality was 9%, with a 60-day mortality of 21%. The most common adverse events were related to myelosuppression. CPX + VEN has activity in RR AML, particularly when used in first salvage and in patients who do not harbor <i>TP53</i> mutations.</p>\u0000 <p>ClinicalTrials.gov Identifier: NCT03629171</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1365-1373"},"PeriodicalIF":10.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114185","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":"PET/CT in the Staging and Treatment Response Assessment of Patients With Extranodal Marginal Zone Lymphoma","authors":"Juan Pablo Alderuccio,&nbsp;Russ A. Kuker,&nbsp;Eduardo Edelman Saul,&nbsp;Michele D. Stanchina,&nbsp;Mark K. Polar,&nbsp;Jennifer Chapman,&nbsp;Wei Zhao,&nbsp;Rafael Hennemann Sassi,&nbsp;Craig H. Moskowitz,&nbsp;Isildinha M. Reis,&nbsp;Izidore S. Lossos","doi":"10.1002/ajh.27712","DOIUrl":"10.1002/ajh.27712","url":null,"abstract":"<p>¹⁸Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality in lymphoma. The 2014 Lugano classification considers extranodal marginal zone lymphoma (EMZL) a non-FDG-avid disease, recommending contrast-enhanced CT. We reassessed the utility of PET/CT for staging workup and response assessment of EMZL. We reviewed staging and response PET/CT of 190 EMZL sites from 152 patients. Each location was counted independently for patients with &gt; 1 extranodal site. Although not standard, we considered FDG-avid disease if SUVmax was ≥ 2, and calculated ratios between lymphoma SUVmax and mediastinal blood pool (BP index) and liver background (liver index). FDG avidity was detected in 151 (79.5%) out of 190 extranodal sites (in 117 [76.7%] out of 152 patients), with a median SUVmax of 4.5 (IQR 2.5–6.9, range 0–26.8). Locations showing FDG avidity in &gt; 90% of extranodal sites included salivary gland, bone, lung, soft tissue, ocular adnexa, and airways. Skin was commonly non-FDG avid (93.8%). Among 22 patients with &gt; 1 extranodal location, there was concordant FDG avidity in all sites in 18 (81.8%) patients. Considering measurable extranodal disease size &gt; 0.5 cm, we observed significant Pearson correlation coefficients (<i>r</i>) between lymphoma size and SUVmax (<i>r</i> = 0.20, <i>p</i> = 0.019, <i>n</i> = 142), BP index (<i>r</i> = 0.34, <i>p</i> &lt; 0.001, <i>n</i> = 124), and liver index (<i>r</i> = 0.36, <i>p</i> &lt; 0.001, <i>n</i> = 124). We also observed improved precision in response to treatment assessment in FDG-avid EMZL tumors. This study demonstrates that EMZL is commonly an FDG-avid disease, suggesting that PET/CT should be routinely used in the staging and response assessment workup of patients with EMZL.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1295-1304"},"PeriodicalIF":10.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}