American Journal of Hematology最新文献

{"title":"Overall Survival in Male Patients With Advanced Hematological Disease (Mostly Acute Leukemia) Is Influenced by CYP1B1 C432G Polymorphism and Donor Sex in Allogeneic Stem Cell Transplantation","authors":"Norbert Stute, Michael Koldehoff","doi":"10.1002/ajh.27538","DOIUrl":"https://doi.org/10.1002/ajh.27538","url":null,"abstract":"<p>Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic key enzyme involved in estrogen metabolism, steroid synthesis, and pro-carcinogen activation. <i>CYP1B1</i> is strongly overexpressed in multiple human malignancies and has been used as a target for cancer chemotherapy and immunotherapy. <i>CYP1B1</i> is also overexpressed in acute lymphocytic leukemia, acute myeloid leukemia, lymphoma, and myeloma [<span>1</span>].</p>\u0000<p>In allogeneic hematopoietic stem cell transplantation (HSCT), disease stage is an established risk factor for overall survival [<span>2</span>]. Our cohort of 118 male patients with advanced disease consisted of advanced forms and stages of AML (<i>n</i> = 47), ALL (<i>n</i> = 17), MDS (<i>n</i> = 12), myeloma (<i>n</i> = 10), CML (<i>n</i> = 9), NHL (<i>n</i> = 8), OMF (<i>n</i> = 6), CLL (<i>n</i> = 6), and CMML (<i>n</i> = 3).</p>\u0000<p>In our recent paper of 382 patients who underwent allogeneic HSCT, we reported a lower overall survival (OS) in male patients with advanced disease (AD) associated with mutant <i>CYP1B1</i> Leu432Val polymorphism (<i>n</i> = 118, <i>p</i> = 0.002): OS 44% ± 8% (CC) vs. 32% ± 6% (CG) vs. 6% ± 6% (GG). Multivariate analysis for OS in male patients with AD revealed <i>CYP1B1</i> polymorphism as the only prognostic factor: RR 1.78, <i>p</i> = 0.001 [<span>1</span>].</p>\u0000<p>We then tested whether donor sex played a role in the outcome of this subgroup of patients and found a surprising result. In our original study we investigated the outcome of male patients with advanced disease (<i>n</i> = 118) and results were stratified by donor sex: male (<i>n</i> = 93) versus female (<i>n</i> = 25). We did not find a major difference in this subgroup of patients by sex mismatch, see supplementary results [<span>1</span>].</p>\u0000<p>An interesting and very different picture emerges when recipient <i>CYP1B1</i> polymorphism (R SNP) data is included in the analysis and the results are stratified by donor sex. In the case of male patients with AD and male donors, the estimated 5-year OS was 47% (wildtype, wt) versus 21% (mutant, mut). Median OS was reached after 4.5 versus 1.2 years (Figure 1A), <i>p</i> = 0.002 (log-rank). For female donors the estimated 5-year OS was 30% (wt) versus 47% (mut) and median OS was reached after 0.6 versus 2.2 years (Figure 1B), not significant. While OS is similar in case of sex mismatch, the difference in OS between wt and mut SNP is biggest if the donor is male. Patients with wt SNP have significantly better results regarding OS with a male donor (<i>n</i> = 93), and worse with a female donor (<i>n</i> = 25). In patients with mut SNP both donor sexes perform poorly. The main finding of our recent analysis (mut R SNP does worse in male patients with advanced disease compared to wt R SNP) is especially true if the donor is male and less so when the donor is female (sex mismatch). There was no difference between mut and wt SNP in male patients with early disease irrespective of th","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"20 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760635","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":"Methotrexate Versus Mycophenolate Mofetil Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Malignancies: A Retrospective Analysis on Behalf of the Chronic Malignancies Working Party of the EBMT","authors":"Thomas Luft,&nbsp;Luuk Gras,&nbsp;Linda Koster,&nbsp;Nicolaus Kröger,&nbsp;Thomas Schröder,&nbsp;Uwe Platzbecker,&nbsp;Katja Sockel,&nbsp;Régis Peffault de Latour,&nbsp;Matthias Stelljes,&nbsp;Henrik Sengeloev,&nbsp;Matthias Eder,&nbsp;Igor Wolfgang Blau,&nbsp;Peter Dreger,&nbsp;Ibrahim Yakoub-Agha,&nbsp;Johan Maertens,&nbsp;Urpu Salmenniemi,&nbsp;Wolfgang Bethge,&nbsp;Stephan Mielke,&nbsp;Guido Kobbe,&nbsp;Anastasia Pouli,&nbsp;Liesbeth C. de Wreede,&nbsp;Kavita Raj,&nbsp;Joanna Drozd-Sokolowska,&nbsp;Donal P. McLornan,&nbsp;Marie Robin","doi":"10.1002/ajh.27531","DOIUrl":"10.1002/ajh.27531","url":null,"abstract":"<div>\u0000 \u0000 <p>Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry-based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX- and MMF-based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX- or MMF prophylaxis in combination with a CNI. Endpoints after allo-HCT were overall survival, relapse-free survival (RFS), relapse incidence, non-relapse mortality (NRM), and Grades 2–4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow-up was 42.8 months (IQR 19.8–74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81–0.95, <i>p</i> = 0.001) and NRM (HR 0.86, 95% CI 0.78–0.96, <i>p</i> = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94–1.14, <i>p</i> = 0.53) or RFS (HR 0.95, 95% CI 0.88–1.01, <i>p</i> = 0.12). There was a reduced risk of Grades 2–4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo-HCT. In conclusion, MTX-complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"38-51"},"PeriodicalIF":10.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738065","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":"Autologous and Allogeneic Stem-Cell Transplantation for Transformed Waldenström Macroglobulinemia","authors":"Eric Durot, Lukshe Kanagaratnam, Saurabh Zanwar, Adrienne Kaufman, Shirley D'Sa, Elise Toussaint, Damien Roos-Weil, Miguel Alcoceba, Josephine M. I. Vos, Anne-Sophie Michallet, Dipti Talaulikar, Efstathios Kastritis, Jahanzaib Khwaja, Steven P. Treon, Ramon Garcia-Sanz, Pierre Morel, Javier Munoz, Jorge J. Castillo, Prashant Kapoor, Alain Delmer","doi":"10.1002/ajh.27543","DOIUrl":"https://doi.org/10.1002/ajh.27543","url":null,"abstract":"&lt;p&gt;Waldenström macroglobulinemia (WM) is characterized by a clonal proliferation of plasmacytoid B-cells in the bone marrow and monoclonal IgM gammopathy, that ultimately require treatment in symptomatic patients. Moreover, a small subset of patients undergoes histological transformation (HT) [&lt;span&gt;1&lt;/span&gt;], mainly in the form of diffuse large B-cell lymphoma (DLBCL). They usually present with high-risk features, such as extranodal involvement, advanced stage, and elevated serum lactate dehydrogenase (LDH) [&lt;span&gt;2&lt;/span&gt;]. Immunochemotherapy (ICT) using anti-CD20 antibodies is commonly used for HT-WM patients, in line with the treatment paradigm for DLBCL. However, the response rates remain low for patients with HT-WM, and the median survival after HT is short (1.5–2.7 years). The role of hematopoietic stem-cell transplantation (HSCT) as consolidation therapy in HT-WM for fit patients is unknown. Data regarding the use of auto and allo-HSCT in transformed indolent lymphomas is limited to retrospective studies of small patient series with heterogeneous populations in terms of the antecedent histologies (predominantly transformed follicular lymphoma), the timing of HSCT (upfront or salvage), or the conditioning regimen. No dedicated study has specifically examined the outcome of patients with HT-WM who received HSCT.&lt;/p&gt;\u0000&lt;p&gt;In this context, results of a large, retrospective, multicenter, international study investigating the clinical course of patients with HT-WM who underwent autologous (auto-HSCT) or allogeneic (allo-HSCT) transplantation are reported here.&lt;/p&gt;\u0000&lt;p&gt;The database collected, comprising 283 patients with HT-WM, treated between January 1995 and December 2021, was compiled through a retrospective investigation of relevant cases in 20 French centers and 9 from other countries. The study protocol was conducted according to the Declaration of Helsinki.&lt;/p&gt;\u0000&lt;p&gt;Response rates were based on positron emission tomography (PET)-scan, according to the Lugano 2014 classification, as addressed by the treating physician (or computed tomography if a PET-scan was not performed). The primary endpoint was overall survival (OS), calculated from the date of HSCT until death from any cause or last follow-up (FU). Progression-free survival (PFS) was calculated from the date of HSCT to relapse, progression, death, or last FU. Other secondary endpoints were the rates of relapse/progression and non-relapse mortality (NRM). PFS and OS probabilities were calculated using Kaplan–Meier estimates and compared using log-rank test. Univariate and multivariate analyses were performed for the cohort of patients who received auto-HSCT fitting Cox proportional-hazard regression models for OS and PFS.&lt;/p&gt;\u0000&lt;p&gt;To study the added utility of auto-HSCT after a complete response (CR) to initial ICT, a cohort of 34 patients younger than 70 years, in CR after first-line therapy for HT-WM without HSCT was used. In this comparison, PFS and OS were calculated from the date of HT-","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"183 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713083","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":"Acute Leukemias of Ambiguous Lineage With MDS-Associated Mutations Show Similar Prognosis Compared to Acute Myeloid Leukemia With MDS-Associated Mutations: A Study From the Bone Marrow Pathology Group","authors":"Timothy J. Kirtek, Weina Chen, Jaryse C. Harris, Adam Bagg, Kathryn Foucar, Wayne Tam, Attilio Orazi, Eric D. Hsi, Robert P. Hasserjian, Sa A. Wang, David P. Ng, Tracy I. George, Min Shi, Kaaren K. Reichard, Emily Symes, Xinmin Zhang, Daniel A. Arber, Olga K. Weinberg","doi":"10.1002/ajh.27537","DOIUrl":"https://doi.org/10.1002/ajh.27537","url":null,"abstract":"&lt;h2&gt;1 Introduction&lt;/h2&gt;\u0000&lt;p&gt;To the Editor: Acute myeloid leukemia (AML) and acute leukemia of ambiguous lineage (ALAL) comprise a diverse variety of acute leukemias that are defined by their morphologic, immunophenotypic, and genetic features. AML is characterized by clonal expansion of immature hematopoietic precursors of myeloid lineage in the peripheral blood and bone marrow. AML may arise de novo, evolve from prior myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), or after exposure to cytotoxic or radiation therapy, called therapy-related AML [&lt;span&gt;1&lt;/span&gt;]. The recent classifications of the World Health Organization (WHO), the 5th Edition Classification of Haematolymphoid Tumours, and the International Consensus Classification of Myeloid and Lymphoid Neoplasms (ICC) both allow for classification of AMLs that arose from, or are otherwise related to, MDS as distinct entities, if diagnostic and exclusionary criteria are met [&lt;span&gt;2, 3&lt;/span&gt;]. These subcategories include AML, myelodysplasia-related in the WHO and AML with myelodysplasia-related gene mutations, or AML with myelodysplasia-related cytogenetic abnormalities in the ICC.&lt;/p&gt;\u0000&lt;p&gt;Both classifications have moved more toward genetically defined classifications of acute leukemias. Both now recognize MDS-associated mutations as defining of MDS-related AML (AML-MR), a disease with poor prognosis. Among the features that define AML-MR are mutations known as secondary-type or MDS-associated mutations, so named because, in the context of AML, they are highly specific for AML arising from preceding MDS, MPNs, or therapy-related clonal aberrations. The presence of mutations in &lt;i&gt;SRSF2&lt;/i&gt;, &lt;i&gt;SF3B1&lt;/i&gt;, &lt;i&gt;U2AF1&lt;/i&gt;, &lt;i&gt;ZRSR2&lt;/i&gt;, &lt;i&gt;ASXL1&lt;/i&gt;, &lt;i&gt;EZH2&lt;/i&gt;, &lt;i&gt;BCOR&lt;/i&gt;, or &lt;i&gt;STAG2&lt;/i&gt; genes is &gt; 95% specific for these “secondary” AMLs [&lt;span&gt;4&lt;/span&gt;]. Somatic mutations in &lt;i&gt;RUNX1&lt;/i&gt; are commonly associated with mutations in other genes characterizing AML-MR and are included in this category in the ICC. AML with mutated &lt;i&gt;RUNX1&lt;/i&gt; is a provisional entity in the WHO 4th edition.&lt;/p&gt;\u0000&lt;p&gt;ALALs have blast populations that either do not show any clear lineage, acute undifferentiated leukemia (AUL), or those that show multi-lineage differentiation, mixed phenotype acute leukemias (MPAL). ALALs are rare, comprising ~4% of acute leukemias, the majority of those being MPAL [&lt;span&gt;3&lt;/span&gt;]. However, leukemias that meet the criteria for other defined categories, such as AMLs with defining genetic abnormalities, are excluded from MPAL. Investigations into the genetic basis of ALAL are limited and have shown great heterogeneity in associated genetic mutations, with some associated with ALL, others with AML, and others with neither. Mutations in MDS-associated genes may be present in a significant proportion of ALAL cases with &lt;i&gt;RUNX1&lt;/i&gt; mutations among the most common [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;The current classifications are unclear on how ALALs should be","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"235 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690765","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":"Basophilia Predicts Poorer Outcomes in Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis, and Myeloproliferative Neoplasm, Unclassifiable","authors":"Lisa Yuen, Tasos Gogakos, Leonardo Boiocchi, Gabriela Hobbs, Robert Hasserjian","doi":"10.1002/ajh.27530","DOIUrl":"https://doi.org/10.1002/ajh.27530","url":null,"abstract":"<p>Basophils are hematopoietic cells derived from myeloid progenitor cells and are found in increased numbers in some myeloid neoplasms, particularly chronic myeloid leukemia (CML). Marked basophilia is a poor prognostic indicator in CML and defines accelerated phase according to the revised 4th edition World Health Organization (WHO4R) classification and the International Consensus Classification (ICC).</p>\u0000<p>Basophilia is less well-documented in the classic <i>BCR::ABL1</i>-negative myeloproliferative neoplasms (MPNs) essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). The clinical behavior of these <i>BCR::ABL1-</i>negative MPNs is heterogeneous, with varying propensity to progress to fibrotic or blast phase. Prior studies have reported that patients with primary or secondary myelofibrosis (MF) with high basophil counts have increased risk of progression to blast phase, shortened survival, and more frequent <i>CALR</i> mutations [<span>1</span>].</p>\u0000<p>The significance of basophilia across ET, PV, and PMF, as well as its association with driver mutations other than the classic <i>JAK2</i> V617F, <i>CALR</i>, and <i>MPL</i>, have not been previously characterized. In the current study, we examined a broad cohort of MPNs to determine associations of basophilia with clinical and molecular features and patient outcome.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"4 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690642","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":"Venetoclax and Hypomethylating Agent in Previously Untreated Higher-Risk Myelodysplastic Syndromes and Genotype Signatures for Response and Prognosis: A Real-World Study","authors":"Jing Wang, Zhijian Fang, Siyi Yang, Kexin Yan, Jingjing Zhang, Yanfang Yu, Yaoliang Ren, Hao Jiang, Jinsong Jia, Jianlin Chen, Botao Li, Yingjun Chang, Xiaosu Zhao, Xiaojun Huang","doi":"10.1002/ajh.27532","DOIUrl":"https://doi.org/10.1002/ajh.27532","url":null,"abstract":"&lt;p&gt;Higher-risk myelodysplastic syndrome (MDS), as defined by the revised international prognostic scoring system (IPSS-R), requires more aggressive treatment. Despite the use of hypomethylating agents (HMAs), response rates remain low, underscoring the need for more effective therapies. Venetoclax is a potent, orally bioavailable inhibitor of the B-cell lymphoma 2 (BCL-2) protein, which acts synergistically with HMAs to target malignant myeloid cells. The combination of venetoclax and HMAs has been approved for the treatment of newly diagnosed acute myeloid leukemia (AML) [&lt;span&gt;1&lt;/span&gt;]. Clinical trials have shown that venetoclax combined with HMAs exhibits efficacy not only in newly diagnosed patients but also in those with relapsed or refractory MDS [&lt;span&gt;2, 3&lt;/span&gt;]. However, real-world data on this combination remain limited, particularly in previously untreated high-risk MDS populations, where genotype signatures for response and prognosis are not yet fully elucidated. Our study aims to address this gap by providing real-world evidence on the efficacy, safety, and genotype-based outcomes of venetoclax plus HMA therapy in this patient population.&lt;/p&gt;\u0000&lt;p&gt;This retrospective, real-world study was conducted at Peking University People's Hospital and Beijing Qinghe Hospital, analyzing the data from a cohort of previously untreated patients with higher-risk MDS who were administered venetoclax in combination with a HMA between January 2020 and February 2024. Eligible participants were adults aged 18 years or older, with a morphological diagnosis of MDS as per the 2016 World Health Organization (WHO) classification, and were stratified as higher-risk according to the IPSS-R (score &gt; 3.5), with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients were excluded if they had incomplete treatment response data, a diagnosis of chronic myelomonocytic leukemia (CMML), or therapy-related MDS. Additionally, patients who were eligible for transplantation were typically not considered for venetoclax and HMA treatment at our center, but those scheduled for transplantation more than 2 months later could receive venetoclax and HMAs while waiting for transplantation if marrow blasts were ≥ 5%. Approval was obtained from the institutional ethics review committee.&lt;/p&gt;\u0000&lt;p&gt;Baseline data, including demographics, disease characteristics, and treatment patterns, were extracted from medical records. Venetoclax was given at 400 mg daily on Days 1–14 of a 28-day cycle, while decitabine (20 mg/m&lt;sup&gt;2&lt;/sup&gt;, d1-5) or azacitidine (75 mg/m&lt;sup&gt;2&lt;/sup&gt;, d1-7) were administered as per standard protocols. Effectiveness outcomes included the objective response rate (ORR), complete response (CR), and event-free survival (EFS), with responses assessed after each treatment cycle according to the International Working Group (IWG) 2006 criteria. EFS was defined as the time to relapse, AML progression, or death, and overall survival (OS) was time to dea","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"27 5 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684535","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":"Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease","authors":"Kadère Konté,&nbsp;Liza Afzali-Hashemi,&nbsp;Koen P. A. Baas,&nbsp;Anouk Schrantee,&nbsp;John C. Wood,&nbsp;Erfan Nur,&nbsp;Aart J. Nederveen,&nbsp;Bart J. Biemond","doi":"10.1002/ajh.27522","DOIUrl":"10.1002/ajh.27522","url":null,"abstract":"<p>Sickle cell disease (SCD) is complicated by silent cerebral infarcts (SCIs), for which anemia is an important risk factor. Despite normal oxygen delivery (OD), cerebral vascular reserve (CVR), and cerebral metabolic rate of oxygen (CMRO₂) are diminished in SCD, possibly causing the formation of SCIs. Voxelotor inhibits polymerization by increasing the hemoglobin oxygen binding, ameliorating hemolytic anemia. Furthermore, anemia is related to cardiac complications. Our aims were to assess the effect of voxelotor on markers of cerebral perfusion, cerebral oxygen metabolism, and markers of cardiac stress in SCD patients. Cerebral hemodynamics and oxygen metabolism were measured with MRI before and after 3 months of voxelotor treatment (1500 mg/day) in 18 adults with SCD (HbSS/HbSβ⁰-thalassemia). Hemoglobin levels significantly increased (<i>p</i> = .001) and markers of hemolysis decreased (<i>p</i> &lt; .05). OD increased from 6.5 (IQR, 6.0–7.1) mL O₂/100 g/min to 8.1 (IQR, 7.2–8.7) mL O₂/100 g/min (<i>p</i> = .001). CBF and CVR did not change. CMRO₂ decreased from 2.0 (IQR, 1.9–2.1) mL O₂/100 g/min to 1.9 (IQR, 1.6–2.1) mL O₂/100 g/min (<i>p</i> = .03). N-terminal pro-B type natriuretic peptide (NT-proBNP) levels decreased (<i>p</i> = .048) and maximum tricuspid regurgitation flow velocity (TRV_max) normalized in all but one patient with increased TRV_max. Voxelotor treatment in patients with severe SCD did not decrease CBF despite increased Hb levels. Cerebral oxygen metabolism slightly decreased, despite raised OD, most likely due to drug-induced increase in oxygen binding. Nonetheless, voxelotor improved clinically validated markers of cardiac stress.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"78-84"},"PeriodicalIF":10.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674479","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":"Treatment-Free Remissions in Children With Chronic Myeloid Leukemia (CML): A Prospective Study From the Tata Memorial Hospital (TMH) Pediatric CML (pCML) Cohort","authors":"Nirmalya Roy Moulik, Swaminathan Keerthivasagam, Gaurav Chatterjee, Jayesh Agiwale, Pallavi Rane, Chetan Dhamne, Akanksha Chichra, Shyam Srinivasan, Purvi Mohanty, Hemani Jain, Dhanlaxmi Shetty, Sweta Rajpal, Prashant Tembhare, Nikhil Patkar, Gaurav Narula, Papagudi G. Subramanian, Shripad Banavali","doi":"10.1002/ajh.27528","DOIUrl":"https://doi.org/10.1002/ajh.27528","url":null,"abstract":"Pediatric chronic myeloid leukemia (pCML) is a rare childhood malignancy, representing 2%–3% of all childhood leukemia. Tyrosine kinase inhibitors (TKIs) have greatly improved survival but pose challenges due to their long-term effects on growth and bone health in children. We prospectively studied treatment-free remission (TFR) in 45 children with pCML in chronic phase on imatinib. Eligibility criteria were as per current NCCN guidelines, with a less stringent qPCR monitoring scheduled every 3 months. TFR was successful in 71.1% (32 out of 45) of patients after a median follow-up of 25 (range: 6–42) months. The TFR rates at 12 and 24 months were 70% and 66%, respectively. Children under 5 years had a TFR rate of 88.9%, compared to 61.8% in those over 5 years (<i>p</i> = 0.18). Eleven of the 13 patients who lost MMR did so within 6 months of discontinuation. The cumulative incidence of loss in MMR at 6, 12, and 24 months was 26.4%, 27%, and 33%, respectively. Ten out of 13 (76.9%) patients with discontinuation failure (DF) regained MMR within 3 (2–20) months of restarting imatinib. A significant correlation was found between higher T-regulatory cell levels at baseline and DF (<i>p</i> = 0.005). More than half patients showed improved bone mineral density after 2 years of TFR. Our findings suggest that high TFR rates can be attained in pCML, with added benefits for bone health. Less frequent molecular monitoring was not associated with adverse outcomes and there seems to be a role of the immune system in sustaining TFR. The study is registered in the Clinical Trials Registry-India (CTRI/2020/11/029199).","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678562","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":"Different impacts of granulocyte colony-stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type","authors":"Takaaki Konuma,&nbsp;Kazuaki Kameda,&nbsp;Kaoru Morita,&nbsp;Tadakazu Kondo,&nbsp;Fumihiko Kimura,&nbsp;Hideki Nakasone,&nbsp;Fumihiko Ouchi,&nbsp;Naoyuki Uchida,&nbsp;Masatsugu Tanaka,&nbsp;Tetsuya Nishida,&nbsp;Takahiro Fukuda,&nbsp;Yuta Hasegawa,&nbsp;Mamiko Sakata-Yanagimoto,&nbsp;Makoto Onizuka,&nbsp;Masashi Sawa,&nbsp;Shuichi Ota,&nbsp;Noboru Asada,&nbsp;Shin-Ichiro Fujiwara,&nbsp;Satoshi Yoshihara,&nbsp;Fumihiko Ishimaru,&nbsp;Makoto Yoshimitsu,&nbsp;Yoshinobu Kanda,&nbsp;Marie Ohbiki,&nbsp;Yoshiko Atsuta,&nbsp;Masamitsu Yanada","doi":"10.1002/ajh.27521","DOIUrl":"10.1002/ajh.27521","url":null,"abstract":"<p>We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II–IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5–10), early initiation (Days 0–4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II–IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II–IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"66-77"},"PeriodicalIF":10.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674913","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":"First-line treatment of Waldenström's macroglobulinemia in Italy: A multicenter real-life study on 547 patients to evaluate the long-term efficacy and tolerability of different chemoimmunotherapy strategies","authors":"Francesco Autore,&nbsp;A. Tedeschi,&nbsp;G. Benevolo,&nbsp;V. Mattiello,&nbsp;E. Galli,&nbsp;N. Danesin,&nbsp;R. Rizzi,&nbsp;J. Olivieri,&nbsp;E. Cencini,&nbsp;B. Puccini,&nbsp;I. Ferrarini,&nbsp;D. Marino,&nbsp;M. Bullo,&nbsp;B. Rossini,&nbsp;M. Motta,&nbsp;I. Innocenti,&nbsp;A. Fresa,&nbsp;L. Stirparo,&nbsp;D. Petrilli,&nbsp;R. Pasquale,&nbsp;P. Musto,&nbsp;G. Scapinello,&nbsp;A. Noto,&nbsp;V. Peri,&nbsp;G. Zamprogna,&nbsp;S. Hohaus,&nbsp;A. M. Frustaci,&nbsp;F. Piazza,&nbsp;S. Ferrero,&nbsp;L. Laurenti","doi":"10.1002/ajh.27524","DOIUrl":"10.1002/ajh.27524","url":null,"abstract":"&lt;p&gt;Treatment is indicated in Waldenström macroglobulinemia (WM) when clinical manifestations arise due to the IgM paraprotein or lymphoplasmacytic infiltrate.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The main classes of drugs used for WM treatment include monoclonal antibodies, chemotherapeutic agents, proteasome inhibitors, and Bruton Tyrosine Kinase inhibitors (BTKi). The most frequently used chemotherapeutic agent is bendamustine, which is largely administered for its efficacy and relatively favorable toxicity profile with low rates of non-hematological adverse events.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Bendamustine plus rituximab (BR) is considered to be especially useful in fit patients in need of rapid disease control.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Rituximab has been evaluated in combination not only with bendamustine (BR), but also with dexamethasone and cyclophosphamide (DRC).&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; A retrospective comparison between BR and DRC was performed at Mayo Clinic, reporting a significantly greater two-year progression free survival (PFS) for BR (88% vs. 61%, respectively) but without a significant difference in overall response rate (ORR) at 18 months (93% vs. 96%, respectively).&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; In contrast, both a superior ORR (98% vs. 85%, respectively) and major response rate (96% vs. 60%, respectively) were reported for BR in the study of Abeykoon et al.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;To further evaluate the efficacy and safety of the different chemoimmunotherapy regimens used for the treatment of WM patients, we conducted a retrospective multicenter study involving 14 different Italian centers of the Fondazione Italiana Linfomi (FIL). The study group included unselected, consecutive WM patients who received frontline treatment with a chemoimmunotherapy regimen between January 2008 and December 2022. Primary outcome measures included ORR, PFS, and OS, as defined by the International Workshop on Waldenström's macroglobulinemia.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Primary outcomes were also assessed based on the total received bendamustine dose, which was categorized using the percentage of the relative dose intensity (RDI). The RDI was calculated for each patient as the percentage of drug actually administered compared to that estimated at the beginning of treatment. The starting dose was 90 mg/m&lt;sup&gt;2&lt;/sup&gt;/day, administered on days 1 and 2 of each of the six planned cycles.&lt;/p&gt;&lt;p&gt;The statistical analyses were conducted on four different treatment groups which included BR, DRC, and two other groups that were named “other R-chemo” and “chemo alone.” The “other R-chemo” group included patients treated with a Rituximab-containing regimen other than BR, such as Chl-R (chlorambucil-rituximab), FCR (fludarabine-cyclophosphamide-rituximab), or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), whereas the “chemo alone” group included patients treated with chemotherapeutic agents such as chlorambucil or cyclophosphamide as singl","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"189-191"},"PeriodicalIF":10.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666905","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}