American Journal of Hematology最新文献

{"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":"<p>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) [<span>1</span>], 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) [<span>2</span>]. 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.</p>\u0000<p>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.</p>\u0000<p>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.</p>\u0000<p>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.</p>\u0000<p>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":"<h2>1 Introduction</h2>\u0000<p>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 [<span>1</span>]. 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 [<span>2, 3</span>]. 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.</p>\u0000<p>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 <i>SRSF2</i>, <i>SF3B1</i>, <i>U2AF1</i>, <i>ZRSR2</i>, <i>ASXL1</i>, <i>EZH2</i>, <i>BCOR</i>, or <i>STAG2</i> genes is > 95% specific for these “secondary” AMLs [<span>4</span>]. Somatic mutations in <i>RUNX1</i> are commonly associated with mutations in other genes characterizing AML-MR and are included in this category in the ICC. AML with mutated <i>RUNX1</i> is a provisional entity in the WHO 4th edition.</p>\u0000<p>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 [<span>3</span>]. 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 <i>RUNX1</i> mutations among the most common [<span>5</span>].</p>\u0000<p>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":"Blood Plasma Methylated DNA Markers in the Detection of Lymphoma: Discovery, Validation, and Clinical Pilot.","authors":"Thomas E Witzig, William R Taylor, Douglas W Mahoney, William R Bamlet, Patrick H Foote, Kelli N Burger, Karen A Doering, Mary E Devens, Jacquelyn R Arndt, Maria C O'Connell, Calise K Berger, Anne J Novak, James R Cerhan, Jacquelyn Hennek, Slava Katerov, Hatim T Allawi, Dragan Jevremovic, Linda N Dao, Rondell P Graham, John B Kisiel","doi":"10.1002/ajh.27533","DOIUrl":"https://doi.org/10.1002/ajh.27533","url":null,"abstract":"<p><p>Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue-derived MDMs of lymphoma in archival plasma specimens. Reduced representation bisulfite sequencing (RRBS) was performed on a discovery set of frozen tissues. MDMs identified were converted to methylation-specific PCR assays and validated on independent formalin-fixed, paraffin-embedded (FFPE) tissues. Target enrichment long-probe quantitative-amplified signal (TELQAS) assays were developed and assayed in plasma-extracted, bisulfite-converted DNA from independent treatment-naïve lymphoma patients and healthy controls. Prediction of cancer status was modeled using random forest model with in silico cross-validation. After discovery and validation in tissue, 16 TELQAS assays (ZNF503, VWA5B1, HOXA9, GABRG3, ITGA5, MAX.chr17.7190, BNC1, CDK20, MAX.chr4.4069, TPBG, DNAH14, SYT6, CACNG8, FAM110B, ADRA1D, and NRN1) were selected for testing in plasma. These detected 78% (95% CI, 74%-82%) of lymphoma cases at 90% specificity. Excluding marginal zone and T-cell lymphomas, sensitivity increased to 84% (80%-88%). MDMs in plasma show promise to detect lymphoma and are candidates for inclusion in multi-cancer detection studies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674912","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}

{"title":"Prognostic significance of mutation type and chromosome fragility in Fanconi anemia.","authors":"María José Ramírez, Roser Pujol, Jordi Minguillón, Massimo Bogliolo, Ilaria Persico, Debora Cavero, Aurora de la Cal, Paula Río, Susana Navarro, José Antonio Casado, Almudena Bailador, Antonio Sanchez de la Fuente, Miguel López de Heredia, Francisco Almazán, M Luisa Antelo, Bienvenida Argilés, Isabel Badell, Marta Baragaño, Cristina Beléndez, Mar Bermúdez, Marta Bernués, María Isabel Buedo, Estela Carrasco, Albert Català, Dolors Costa, Isabel Cuesta, Rafael Fernandez-Delgado, Ana Fernández-Teijeiro, Ángela Figuera, Marta García, Ainhoa Gondra, Macarena González, Soledad González Muñiz, Ines Hernández-Rodríguez, Fátima Ibañez, Nicholas John Kelleher, Francisco Lendínez, Mónica López, Ricardo López-Almaraz, Inmaculada Marchante, Carmen Mendoza, José Nieto, Emilio Ojeda, Salvador Payán-Pernía, Irene Peláez, Inmaculada Pérez de Soto, Raquel Portugal, María A Ramos-Arroyo, Alexandra Regueiro, Ana Rodríguez, Jordi Rosell, Raquel Saez, José Sánchez, Martha Sánchez, MªLeonor Senent, María Tapia, Juan Pablo Trujillo-Quintero, José Manuel Vagace, Jaime Verdú-Amorós, Victória Verdugo, Isabel Vidales, Jasson Villarreal, Cristina Díaz-de-Heredia, Julián Sevilla, Juan Antonio Bueren, Jordi Surrallés","doi":"10.1002/ajh.27520","DOIUrl":"https://doi.org/10.1002/ajh.27520","url":null,"abstract":"<p><p>Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later-onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG, with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA. Clinical Trial Registration number: NCT06490510.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674485","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}