Leukemia research最新文献_第10页

Phase 1 study of azacitidine in combination with quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN 阿扎胞苷联合奎沙替尼治疗 FLT3 或 CBL 突变 MDS 和 MDS/MPN 患者的 1 期研究

IF 2.7 4区医学

Leukemia research Pub Date : 2024-05-11 DOI: 10.1016/j.leukres.2024.107518

Guillermo Montalban-Bravo , Elias Jabbour , Kelly Chien , Danielle Hammond , Nicholas Short , Farhad Ravandi , Marina Konopleva , Gautam Borthakur , Naval Daver , Rashmi Kanagal-Shammana , Sanam Loghavi , Wei Qiao , Xuelin Huang , Heather Schneider , Meghan Meyer , Hagop Kantarjian , Guillermo Garcia-Manero

{"title":"Phase 1 study of azacitidine in combination with quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN","authors":"Guillermo Montalban-Bravo , Elias Jabbour , Kelly Chien , Danielle Hammond , Nicholas Short , Farhad Ravandi , Marina Konopleva , Gautam Borthakur , Naval Daver , Rashmi Kanagal-Shammana , Sanam Loghavi , Wei Qiao , Xuelin Huang , Heather Schneider , Meghan Meyer , Hagop Kantarjian , Guillermo Garcia-Manero","doi":"10.1016/j.leukres.2024.107518","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107518","url":null,"abstract":"<div><p>We conducted a phase 1 study evaluating 3 dose levels of quizartinib (30 mg, 40 mg or 60 mg) in combination with azacitidine for HMA-naïve or relapsed/refractory MDS or MDS/MPN with <em>FLT3</em> or <em>CBL</em> mutations. Overall, 12 patients (HMA naïve: n=9, HMA failure: n=3) were enrolled; 7 (58 %) patients had <em>FLT3</em> mutations and 5 (42 %) had <em>CBL</em> mutations. The maximum tolerated dose was not reached. Most common grade 3–4 treatment-emergent adverse events were thrombocytopenia (n=5, 42 %), anemia (n=4, 33 %), lung infection (n=2, 17 %), skin infection (n=2, 17 %), hyponatremia (n=2, 17 %) and sepsis (n=2, 17 %). The overall response rate was 83 % with median relapse-free and overall survivals of 15.1 months (95 % CI 0.0–38.4 months) and 17.5 months (95 % CI NC-NC), respectively. <em>FLT3</em> mutation clearance was observed in 57 % (n=4) patients. These data suggest quizartinib is safe and shows encouraging activity in <em>FLT3</em>-mutated MDS and MDS/MPN. This study is registered at Clinicaltrials.gov as NCT04493138.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"142 ","pages":"Article 107518"},"PeriodicalIF":2.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma 复发/难治性滤泡性淋巴瘤遗传学和免疫生物学的转化研究。

IF 2.7 4区医学

Leukemia research Pub Date : 2024-05-11 DOI: 10.1016/j.leukres.2024.107519

Benyamin Yaniv , Benjamin Tanenbaum , Vera Kazakova , Shyam A. Patel

{"title":"Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma","authors":"Benyamin Yaniv , Benjamin Tanenbaum , Vera Kazakova , Shyam A. Patel","doi":"10.1016/j.leukres.2024.107519","DOIUrl":"10.1016/j.leukres.2024.107519","url":null,"abstract":"<div><p>Although follicular lymphoma (FL) is traditionally classified as an indolent subtype of B cell non-Hodgkin lymphoma, clinical trajectories are often diverse based on unique disease biology, and many patients will eventually experience relapse of their disease. Furthermore, progression of disease within 24 months is associated with increased mortality rates for FL. In the last five years, we have witnessed an upsurge in the commercial availability of targeted therapies for relapsed/refractory (R/R) FL, including chimeric antigen receptor-T (CAR-T) products, bispecific T cell engagers (BiTEs), epigenetic modifier therapies, and next-generation Bruton tyrosine kinase (BTK) inhibitors. Furthermore, clinical trial options have increased tremendously and now include combinatorial strategies that exert synergy against malignant germinal center B cells. Here, we provide a 2024 update of novel therapeutic agents whose development has been informed by recent advances in the genetics and immunobiology of R/R FL. Specifically, we emphasize high-value targeted therapeutics, including anti-CD3 x anti-CD20 BiTEs and adoptive T cell therapies. We discuss prospects on selection and sequencing of BiTEs and CAR-T therapies for patients with R/R FL. We underscore the principles of FL pathobiology that are paving way for future drug discovery and shed insight into therapeutic targeting within nodal basins based on our increasing understanding of the FL microenvironment. Finally, we summarize how a greater knowledge of FL immunobiology can inform risk stratification and therapy selection on a personalized basis for R/R FL in 2025.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"142 ","pages":"Article 107519"},"PeriodicalIF":2.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation 氟马替尼治疗新诊断的慢性髓性白血病慢性期的疗效和安全性：以过早停药为重点的真实世界单中心回顾性研究

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-26 DOI: 10.1016/j.leukres.2024.107507

Mingshan Sun, Shijie Li, Zhenyi Liu, Sai Ma, Xiaohan Liu, Qing Meng, Yueyue Zheng, Chunyan Chen

{"title":"Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation","authors":"Mingshan Sun, Shijie Li, Zhenyi Liu, Sai Ma, Xiaohan Liu, Qing Meng, Yueyue Zheng, Chunyan Chen","doi":"10.1016/j.leukres.2024.107507","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107507","url":null,"abstract":"<div><h3>Purpose</h3><p>To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP).</p></div><div><h3>Results</h3><p>Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3–4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival.</p></div><div><h3>Conclusions</h3><p>Flumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"142 ","pages":"Article 107507"},"PeriodicalIF":2.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC) monitoring 急性髓性白血病（AML）和高级别骨髓增生异常综合征（MDS）异基因干细胞移植（allo-SCT）后的供者淋巴细胞输注（DLI）。使用外周血（PB）CD34+和CD3+供体嵌合体（DC）监测的纵向回顾性研究

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-24 DOI: 10.1016/j.leukres.2024.107504

Tishya Indran , Tongted Das , Jenny Muirhead , Maureen O’Brien , Michael I. Swain , Bianca Cirone , Jaqueline Widjaja , Sushrut Patil , David J. Curtis

{"title":"Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC) monitoring","authors":"Tishya Indran , Tongted Das , Jenny Muirhead , Maureen O’Brien , Michael I. Swain , Bianca Cirone , Jaqueline Widjaja , Sushrut Patil , David J. Curtis","doi":"10.1016/j.leukres.2024.107504","DOIUrl":"10.1016/j.leukres.2024.107504","url":null,"abstract":"<div><h3>Introduction</h3><p>This longitudinal study was based on the outcomes of Donor Lymphocyte Infusion (DLI) for falling peripheral blood (PB) CD34<sup>+</sup> and CD3<sup>+</sup> donor chimerism (DC).</p></div><div><h3>Methods</h3><p>From 2012 to 2018, data was collected from the BMT database and electronic medical records (EMR). The primary objective was to compare the indication for DLI based on falling PB CD34<sup>+</sup> or CD3<sup>+</sup> DC in patients post allo-SCT for AML and MDS and their overall survival (OS).</p></div><div><h3>Results</h3><p>18/70 patients met the inclusion criteria. Indications for DLI were i) falling PB CD34<sup>+</sup> DC ≤ 80 % with morphological relapse, ii) falling PB CD34<sup>+</sup> DC ≤ 80 % without morphological relapse and iii) falling PB CD3<sup>+</sup> DC ≤ 80 % without falling PB CD34<sup>+</sup> DC. Log rank analysis showed falling PB CD34<sup>+</sup> DC and morphological relapse had significantly lower OS. Linear regression demonstrated better OS post DLI if there was PB CD34<sup>+</sup> and CD3<sup>+</sup> chimerism response at 30 days (p = 0.029), GVHD (p = 0.032) and tapering immunosuppression at the time of falling DC (p = 0.042).</p></div><div><h3>Conclusion</h3><p>DLI for PB CD34<sup>+</sup> DC values ≤ 80 % and morphological relapse had the lowest OS. In this study, full DC was achieved after DLI even with a PB CD3<sup>+</sup>DC value as low as 13 %, provided the PB CD34<sup>+</sup> DC remained > 80 %. Further research is vital in CD34<sup>+</sup> DC as a biomarker for disease relapse and loss of engraftment.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"142 ","pages":"Article 107504"},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140778602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes 青少年和成人中接受强化治疗的 t (1; 19) (q23; p13)/TCF3::PBX1 B ALL 的实际疗效

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-18 DOI: 10.1016/j.leukres.2024.107506

Tribikram Panda, Sujay Rainchwar, Reema Singh, Aakanksha Singh, Mayank Soni, Disha Kakkar, KR Jegan, Reshmi Harikumar Pillai, Roy J. Palatty, Karuna Jha, Rayaz Ahmed, Rohan Halder, Narender Tejwani, Devasis Panda, Dinesh Bhurani, Narendra Agrawal

{"title":"Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes","authors":"Tribikram Panda, Sujay Rainchwar, Reema Singh, Aakanksha Singh, Mayank Soni, Disha Kakkar, KR Jegan, Reshmi Harikumar Pillai, Roy J. Palatty, Karuna Jha, Rayaz Ahmed, Rohan Halder, Narender Tejwani, Devasis Panda, Dinesh Bhurani, Narendra Agrawal","doi":"10.1016/j.leukres.2024.107506","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107506","url":null,"abstract":"<div><p>Significant heterogeneity has been reported in outcome of Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3::PBX1 in adolescents and adults leading to a lack of consensus on precise risk stratification. We evaluated clinical outcome of 17 adult ALL cases (≥15 years) with this genotype treated on intensive regimes.13/17 received COG0232 and 4/17 cases received UK-ALL protocol. All achieved CR (100%) with above treatment. End of induction MRD was evaluated in 14/17 cases of which 11 (78.5%) achieved MRD negativity. Total nine patients relapsed (7 marrows, 2 CNS). Overall survival at 2 years was 53.3%. The 2 year estimated PFS was 42.9%. The 2 years CIR was 54.2%. Adults with this genotype perform poorly despite early favorable response. Incorporation of novel immunotherapies and prompt HSCT should be strongly considered with this genotype. Targeted NGS panels for additional genetic aberrations can further help in risk stratifying and guiding therapy for this genotype.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107506"},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed/refractory acute myeloid leukemia 治疗复发/难治性急性髓性白血病患者的第二代FLT3抑制剂系统综述

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-17 DOI: 10.1016/j.leukres.2024.107505

Alireza Mohebbi , Fahimeh Shahriyary , Vida Farrokhi , Bita Bandar , Najmaldin Saki

{"title":"A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed/refractory acute myeloid leukemia","authors":"Alireza Mohebbi , Fahimeh Shahriyary , Vida Farrokhi , Bita Bandar , Najmaldin Saki","doi":"10.1016/j.leukres.2024.107505","DOIUrl":"10.1016/j.leukres.2024.107505","url":null,"abstract":"<div><h3>Background</h3><p>Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML.</p></div><div><h3>Methods</h3><p>A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA.</p></div><div><h3>Results</h3><p>The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients.</p></div><div><h3>Conclusion</h3><p>These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107505"},"PeriodicalIF":2.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction of deep molecular response in chronic myeloid leukemia using supervised machine learning models 利用监督机器学习模型预测慢性髓性白血病的深度分子反应

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-15 DOI: 10.1016/j.leukres.2024.107502

Zahra Zad , Simone Bonecker , Taiyao Wang , Ilana Zalcberg , Gustavo T. Stelzer , Bruna Sabioni , Luciana Mayumi Gutiyama , Julia L. Fleck , Ioannis Ch. Paschalidis

引用次数: 0

Racial and ethnic disparities in Acute Myeloid Leukemia: 15-year experience at a safety net hospital system 急性髓性白血病的种族和民族差异：一家安全网医院系统 15 年的经验

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-15 DOI: 10.1016/j.leukres.2024.107503

Sharlene Dong , Naveen Premnath , Navid Sadeghi , Radhika Kainthla , Stephen S. Chung , Robert H. Collins , Hsiao C. Li , Yazan F. Madanat

{"title":"Racial and ethnic disparities in Acute Myeloid Leukemia: 15-year experience at a safety net hospital system","authors":"Sharlene Dong , Naveen Premnath , Navid Sadeghi , Radhika Kainthla , Stephen S. Chung , Robert H. Collins , Hsiao C. Li , Yazan F. Madanat","doi":"10.1016/j.leukres.2024.107503","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107503","url":null,"abstract":"<div><p>Despite recent therapeutic advances, ethnic minorities in the U.S. continue to have disproportionately poor outcomes in many hematologic malignancies including AML. We identified 162 adult AML patients treated at a non-transplant safety net hospital from 2007 to 2022 and evaluated differences in disease characteristics, treatment and clinical outcomes based on race and ethnicity. Our cohort consisted of 82 (50.6%) Hispanic, 36 (22.2%) non-Hispanic black and 44 (27.2%) non-Hispanic white and Asian patients. Median age at diagnosis was 42.5, 49.0 and 52.5 years respectively (p=0.025). Hispanics had higher rates of intermediate and high-risk disease (p=0.699) and received high intensity induction and consolidation chemotherapy at lower rates (p=0.962), although differences did not reach statistical significance. Despite this, similar remission rates were achieved. Hispanics with high-risk disease had longer overall survival (OS) than the combined non-Hispanic cohort (mOS 14 m vs 7 m, p=0.030). Multivariate regression analysis showed that OS was negatively associated with age (HR 1.023, p=0.006), intermediate (HR 3.431, p=0.0003) and high-risk disease (HR 4.689, p<0.0001) and positively associated with Hispanic ethnicity (HR 0.614, p=0.026). This report suggests that contrary to other studies, Hispanics, particularly those with high-risk AML, may have improved OS compared to other ethnic groups. These results are unique to our safety net hospital setting where common barriers to medical care and healthcare disparities are largely mitigated.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107503"},"PeriodicalIF":2.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia 接受 VEN-AZA 治疗的新诊断急性髓性白血病患者 SRSF2 基因突变预后不佳

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-15 DOI: 10.1016/j.leukres.2024.107500

Guillaume Berton , Bochra Sedaki , Erwann Collomb , Sami Benachour , Michael Loschi , Bilal Mohty , Colombe Saillard , Yosr Hicheri , Camille Rouzaud , Valerio Maisano , Ferdinand Villetard , Evelyne D.'Incan Corda , Aude Charbonnier , Jerome Rey , Marie-Anne Hospital , Antoine Ittel , Norman Abbou , Raphaelle Fanciullino , Bérengère Dadone-Montaudié , Norbert Vey , Sylvain Garciaz

{"title":"Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia","authors":"Guillaume Berton , Bochra Sedaki , Erwann Collomb , Sami Benachour , Michael Loschi , Bilal Mohty , Colombe Saillard , Yosr Hicheri , Camille Rouzaud , Valerio Maisano , Ferdinand Villetard , Evelyne D.'Incan Corda , Aude Charbonnier , Jerome Rey , Marie-Anne Hospital , Antoine Ittel , Norman Abbou , Raphaelle Fanciullino , Bérengère Dadone-Montaudié , Norbert Vey , Sylvain Garciaz","doi":"10.1016/j.leukres.2024.107500","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107500","url":null,"abstract":"<div><p>Mutations in spliceosome genes (<em>SRSF2</em>, <em>SF3B1</em>, <em>U2AF1</em>, <em>ZRSR2)</em> correlate with inferior outcomes in patients treated with intensive chemotherapy for Acute Myeloid Leukemia. However, their prognostic impact in patients treated with less intensive protocols is not well known. This study aimed to evaluate the impact of Spliceosome mutations in patients treated with Venetoclax and Azacitidine for newly diagnosed AML. 117 patients treated in 3 different hospitals were included in the analysis. 34 harbored a mutation in at least one of the spliceosome genes (splice-mut cohort). K/NRAS mutations were more frequent in the splice-mut cohort (47% vs 19%, p=0.0022). Response rates did not differ between splice-mut and splice-wt cohorts. With a median follow-up of 15 months, splice mutations were associated with a lower 18-month LFS (p=0.0045). When analyzing splice mutations separately, we found SRSF2 mutations to be associated with poorer outcomes (p=0.034 and p=0.037 for OS and LFS respectively). This negative prognostic impact remained true in our multivariate analysis. We believe this finding should warrant further studies aimed at overcoming this negative impact.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107500"},"PeriodicalIF":2.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624000663/pdfft?md5=4d4e114f1e8bcfb3607ca62b5c9babbc&pid=1-s2.0-S0145212624000663-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study 捐献者很重要：捐献者选择对西班牙裔B细胞急性淋巴细胞白血病患者造血干细胞移植结果的影响：一项髓鞘脱落造血干细胞移植研究的启示

IF 2.7 4区医学

Leukemia research Pub Date : 2024-04-12 DOI: 10.1016/j.leukres.2024.107501

Karam Ashouri , Anush A. Ginosyan , Mollee Chu , Brian Hom , Jennifer Hwang , Karen Resnick , Yekta Rahimi , Preet Chaudhary , Karrune Woan , Imran Siddiqi , Abdullah Ladha , Amir Ali , Eric Leon Tam , George Yaghmour

{"title":"Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study","authors":"Karam Ashouri , Anush A. Ginosyan , Mollee Chu , Brian Hom , Jennifer Hwang , Karen Resnick , Yekta Rahimi , Preet Chaudhary , Karrune Woan , Imran Siddiqi , Abdullah Ladha , Amir Ali , Eric Leon Tam , George Yaghmour","doi":"10.1016/j.leukres.2024.107501","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107501","url":null,"abstract":"<div><h3>Background</h3><p>Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients.</p></div><div><h3>Methodology</h3><p>This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023.</p></div><div><h3>Results</h3><p>Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036).</p></div><div><h3>Conclusion</h3><p>Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107501"},"PeriodicalIF":2.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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