Leukemia researchPub Date : 2025-06-02DOI: 10.1016/j.leukres.2025.107724
Muhammad Kashif Amin , Muhammad Atif Khan , Faiza Humayun Khan , Asma Zakir , Muayad Azzam , Reem Mustafa , Talha Badar
{"title":"Impact of FLT3 inhibitors on the outcomes of FLT3-ITD mutated acute myeloid leukemia following allogeneic hematopoietic stem cell transplant: A systematic review and meta-analysis","authors":"Muhammad Kashif Amin , Muhammad Atif Khan , Faiza Humayun Khan , Asma Zakir , Muayad Azzam , Reem Mustafa , Talha Badar","doi":"10.1016/j.leukres.2025.107724","DOIUrl":"10.1016/j.leukres.2025.107724","url":null,"abstract":"<div><h3>Background</h3><div>Acute Myeloid Leukemia (AML) with FLT3-ITD mutations is associated with high post-transplant relapse rates. FLT3 inhibitor (FLT3i) maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HCT) has emerged as a promising strategy to improve outcomes in this high-risk population.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating FLT3i maintenance therapy versus standard of care (SOC) after allo-HCT in patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A comprehensive search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was performed in accordance with PRISMA guidelines. Primary outcomes included relapse-free survival (RFS), overall survival (OS), and FLT3i-related adverse events. Pooled hazard ratios (HRs) and relative risks (RRs) were calculated using the “meta” package in R (version 4.4.0).</div></div><div><h3>Results</h3><div>Four RCTs including 701 patients (ages 18–78) met inclusion criteria. FLT3i maintenance significantly reduced relapse (HR 0.50; 95 % CI: 0.34–0.74) and mortality (HR 0.63; 95 % CI: 0.44–0.91) compared to SOC. Hematologic toxicity (RR 2.12; 95 % CI: 1.67–2.70) and chronic GVHD (RR 1.18; 95 % CI: 1.00–1.41) were more frequent in the FLT3i group. Rates of acute GVHD (RR 1.05; 95 % CI: 0.78–1.41) and hepatotoxicity (RR 1.09; 95 % CI: 0.72–1.66) were comparable. Interestingly, skin toxicity was lower with FLT3i (RR 0.36; 95 % CI: 0.16–0.84).</div></div><div><h3>Conclusion</h3><div>FLT3i maintenance significantly improves RFS and OS in FLT3-ITD-mutated AML post-allo-HCT, though at the cost of increased hematologic toxicity and chronic GVHD. Further studies are needed to define optimal agents, duration, and patient selection to balance efficacy with tolerability.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107724"},"PeriodicalIF":2.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223683","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}
Leukemia researchPub Date : 2025-06-02DOI: 10.1016/j.leukres.2025.107717
Brian A. Jonas , Samantha C. Fisch , Peter T. Curtin , Gary J. Schiller , Deepa Jeyakumar , Dimitrios Tzachanis , Rafael Bejar , Lihong Qi , Matthew J. Wieduwilt , Joseph M. Tuscano , Lloyd Damon , Aaron C. Logan , for the University of California Hematologic Malignancies Consortium
{"title":"A phase 1 trial of ibrutinib and azacitidine for higher risk myelodysplastic syndromes (University of California Hematologic Malignancies Consortium Study 1503)","authors":"Brian A. Jonas , Samantha C. Fisch , Peter T. Curtin , Gary J. Schiller , Deepa Jeyakumar , Dimitrios Tzachanis , Rafael Bejar , Lihong Qi , Matthew J. Wieduwilt , Joseph M. Tuscano , Lloyd Damon , Aaron C. Logan , for the University of California Hematologic Malignancies Consortium","doi":"10.1016/j.leukres.2025.107717","DOIUrl":"10.1016/j.leukres.2025.107717","url":null,"abstract":"<div><div>Despite the use of hypomethylating agents (HMA), outcomes remain poor for patients with higher-risk myelodysplastic syndromes (HR-MDS). Ibrutinib (IBR) is a Bruton’s Tyrosine Kinase (BTK) inhibitor that can exert anti-myeloblast activity through inhibition of NF-kB signaling. IBR also has immunomodulatory activity through binding to interleukin-2-inducible kinase (ITK). We conducted a multicenter Phase 1b trial (NCT02553941) to evaluate the safety, tolerability, and preliminary efficacy of the combination of IBR and azacitidine (AZA) in patients with HR-MDS. Patients received standard AZA in combination with IBR at two dose levels (DL), 420 mg (DL1) and 560 mg (DL2). Twenty-one patients were enrolled, including 17 with high- or very high-risk disease and six with prior HMA therapy. No dose-limiting toxicities were observed in the dose escalation cohorts. The most common grade 3 or higher adverse events included thrombocytopenia, neutropenia, anemia, and febrile neutropenia. Bleeding events occurred in 14 patients (67 %), with a grade 3 event in one patient. The overall response rate was 48 %, including 3 (14 %) complete remissions (CR) and 4 (19 %) marrow CR. Responses were seen in patients with <em>TP</em>53 mutations or deletions. CD34 positive bone marrow mononuclear cells (BMMC) BTK and peripheral blood MC (PBMC) ITK occupancy by IBR demonstrated on-target activity in relevant target cells. In patients with HR-MDS, the combination of IBR and AZA is safe, tolerable, and active, including responses in patients with <em>TP</em>53 aberrations and with prior HMA therapy. Further study in a larger, randomized trial is necessary to assess efficacy of this regimen for patients with HR-MDS.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107717"},"PeriodicalIF":2.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223682","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}
{"title":"Treatment strategy for indolent adult T-cell leukemia-lymphoma","authors":"Takeharu Kato , Yoshitaka Imaizumi , Yasushi Miyazaki","doi":"10.1016/j.leukres.2025.107714","DOIUrl":"10.1016/j.leukres.2025.107714","url":null,"abstract":"<div><div>Adult T-cell leukemia-lymphoma (ATL), a distinct peripheral T-lymphocytic malignancy associated with human T-lymphotropic virus type-1, can be classified into four subtypes based on clinical manifestations: acute, lymphoma, chronic, and smoldering types. The smoldering and chronic types without poor prognostic factors are classified as indolent ATL. Watchful waiting until disease progression and skin-directed therapy have been recommended as standard treatment strategies, and combination therapy with interferon-alpha and the antiviral drug zidovudine may be used in some cases. High-risk cases for prognosis, identified based on prognostic scores such as Indolent ATL-Prognostic index (iATL-PI) and various biomarkers, should be carefully monitored. Furthermore, early intervention methods must be developed and validated for these cases.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107714"},"PeriodicalIF":2.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261823","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}
Leukemia researchPub Date : 2025-05-28DOI: 10.1016/j.leukres.2025.107722
Sabrina Haslinger , Dagmar Schinnerl , Margit König, Andrea Inthal, Klaus Fortschegger, Stefan Köhrer, Margarita Maurer-Granofszky, Andishe Attarbaschi, Karin Nebral, Sabine Strehl
{"title":"Identification of a novel amplified PAX5::RBPMS fusion gene in pediatric B-cell acute lymphoblastic leukemia","authors":"Sabrina Haslinger , Dagmar Schinnerl , Margit König, Andrea Inthal, Klaus Fortschegger, Stefan Köhrer, Margarita Maurer-Granofszky, Andishe Attarbaschi, Karin Nebral, Sabine Strehl","doi":"10.1016/j.leukres.2025.107722","DOIUrl":"10.1016/j.leukres.2025.107722","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"154 ","pages":"Article 107722"},"PeriodicalIF":2.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203495","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}
Leukemia researchPub Date : 2025-05-26DOI: 10.1016/j.leukres.2025.107721
Xingying Li , Yu Cai , Jun Yang , Chongmei Huang , Xiaowei Xu , Huiying Qiu , Jiahua Niu , Kun Zhou , Ying Zhang , Xinxin Xia , Yu Wei , Chang Shen , Yin Tong , Baoxia Dong , Liping Wan , Xianmin Song
{"title":"Parous female donor is not inferior to the young male donor under the low-dose ATG/PTCy combination-based regimen for GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation","authors":"Xingying Li , Yu Cai , Jun Yang , Chongmei Huang , Xiaowei Xu , Huiying Qiu , Jiahua Niu , Kun Zhou , Ying Zhang , Xinxin Xia , Yu Wei , Chang Shen , Yin Tong , Baoxia Dong , Liping Wan , Xianmin Song","doi":"10.1016/j.leukres.2025.107721","DOIUrl":"10.1016/j.leukres.2025.107721","url":null,"abstract":"<div><h3>Background</h3><div>An optimal donor is critical for patient survival undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The impacts of different donors on outcomes under the combination regimens of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis had limited data. Methods: Therefore, a single-center retrospective study was performed for patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with ATG/PTCy combination-based regimen. Results: The donors were divided into young male (age <30 years, n = 74), non-parous female (age <30 years, n = 22), older male (age ≥30 years, n = 117), and parous female (age ≥30 years, n = 42) donor groups. The cumulative incidences (CIs) of acute and chronic GVHD, and survival outcomes were similar between the 4 groups (P > 0.050), while the parous female donor could significantly reduce the cumulative incidence of relapse (CIR). Conclusions: The results showed that the parous female donor could significantly reduce CIR and might improve survival under the ATG and PTCy combination-based GVHD prophylaxis regimen after haplo-PBSCT.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"154 ","pages":"Article 107721"},"PeriodicalIF":2.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168242","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}
{"title":"Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: Real-life study from the French CML group Fi-LMC","authors":"Hyacinthe Johnson-Ansah , Aude Charbonnier , Gabriel Etienne , Lydia Roy , Laurence Legros , Gabrielle Roth-Guépin , Corentin Orvain , Anne Bouvier , Emilie Cayssials , Valérie Coiteux , Philippe Rousselot , Dina Naguib , Gandhi Damaj , Delphine Lebon , François-Xavier Mahon , Pascale Flandrin-Gresta , Stéphanie Dulucq , Sandrine Hayette , Jean-Michel Cayuela , Franck-Emmanuel Nicolini , Delphine Rea","doi":"10.1016/j.leukres.2025.107716","DOIUrl":"10.1016/j.leukres.2025.107716","url":null,"abstract":"<div><div>Tyrosine kinase inhibitors of the BCR::ABL1 oncoprotein can be stopped without subsequent molecular relapse or major safety concerns in 40–80 % of adult patients with P210<sup>BCR::ABL1</sup> positive chronic myeloid leukemia with sustained deep molecular responses. In contrast, ending treatment in patients with rare rearrangements located outside the major <em>BCR</em> region or within the exon 3 of <em>ABL1</em> remains to be explored. Twenty-four patients with chronic phase disease and diverse uncommon <em>BCR::ABL1</em> transcripts who obtained sustained molecular residual disease negativity and stopped therapy in a real-life setting for various reasons were retrospectively evaluated for treatment-free remission determinants. Six patients relapsed after a median time of 6 months (range; 3–49), relapse being defined as a rise in molecular residual disease above the 3-log threshold. Treatment-free remission probabilities at 12 and 60 months were 83.3 % (95 % CI: 68.4–98.2 %) and 70.6 % (95 % CI: 49.5–91.6), respectively. The type of <em>BCR::ABL1</em> transcript was the only relevant baseline factor associated with durable treatment-free remission and patients with fusions lacking exon a2 sequences had the best outcome. To conclude, treatment-free remission is a reasonably achievable goal in patients with rare <em>ABL1</em> fusion transcripts. Our results pave the way for recommendations in clinical practice. Nevertheless, further research is needed to determine which patients have highest chances to reach deep molecular response levels and become free from therapy and to decipher the biological impact of the different molecular rearrangements of <em>BCR::ABL1</em> on treatment-free remission.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"154 ","pages":"Article 107716"},"PeriodicalIF":2.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106831","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}
Leukemia researchPub Date : 2025-05-13DOI: 10.1016/j.leukres.2025.107718
Laurenz Steiner , Navkirandeep Kaur , Johann-Christoph Jann , Alice Fabarius , Georgia Metzgeroth , Manja Meggendorfer , Wolf-Karsten Hofmann , Mohamad Jawhar , Daniel Nowak , Alexander Streuer
{"title":"Inter-modality variance of blast quantification in patients with myelodysplastic neoplasms (MDS) and its impact on risk stratification and overall survival","authors":"Laurenz Steiner , Navkirandeep Kaur , Johann-Christoph Jann , Alice Fabarius , Georgia Metzgeroth , Manja Meggendorfer , Wolf-Karsten Hofmann , Mohamad Jawhar , Daniel Nowak , Alexander Streuer","doi":"10.1016/j.leukres.2025.107718","DOIUrl":"10.1016/j.leukres.2025.107718","url":null,"abstract":"<div><div>In the revised International Prognostic Scoring System (IPSS-R), blast enumeration by bone marrow cytology (BM-c) is crucial for risk stratification in myelodysplastic neoplasms (MDS), in the IPSS-Molecular (IPSS-M) however, incorporation of molecular data gained more prognostic impact. Blast count differences in the commonly used methods BM-c, flow cytometry (BM-f) and histology (BM-h) could possibly impact categorisation and overall survival (OS). In n = 145 investigated cases treated since 2012 in our institution, discordance in IPSS-R blast categories was found in 62/145 (43 %) of cases with evaluable blast counts in ≥ 2 methods. Discordant cases scored by BM-c showed either no change (24 %), a downgrade (48 %) or an upgrade (28 %) of their IPSS-R category when applying BM-f or BM-h. Discordant LR-MDS patients had significantly worse OS than concordant (72 vs 35 months, p = 0.031). In contrast, stratification by IPSS-M revealed no OS difference for discordant LR-MDS patients (p = 0.46). We could demonstrate that discordance occurred in almost half of patients, leading to re-stratification in a substantial amount of cases. Furthermore, OS was worse for discordant patients, but differences were ameliorated by inclusion of molecular data. This highlights the growing importance of molecular data over blast quantification in MDS.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"154 ","pages":"Article 107718"},"PeriodicalIF":2.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068045","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}
Leukemia researchPub Date : 2025-05-13DOI: 10.1016/j.leukres.2025.107715
Sabrina Mariani , Luca Maurillo , Monica Piedimonte, Chiara Sarlo, Luana Fianchi, Francesco Buccisano, Maria Teresa Voso, Susanna Fenu, Anna Lina Piccioni, Tommaso Caravita di Toritto, Ida Carmosino, Laura Cicconi, Alessandro Pulsoni, Michelina Santopietro, Roberto Latagliata, Ambra Di Veroli, Emiliano Fabiani, Martina Quattrone, Flavia Mallegni, Francesca Romana Iovene, Agostino Tafuri
{"title":"Luspatercept in lower-myelodysplastic syndromes (MDS): Real-world data from the Gruppo Romano-Laziale Mielodisplasie (GROM-L) and review of literature","authors":"Sabrina Mariani , Luca Maurillo , Monica Piedimonte, Chiara Sarlo, Luana Fianchi, Francesco Buccisano, Maria Teresa Voso, Susanna Fenu, Anna Lina Piccioni, Tommaso Caravita di Toritto, Ida Carmosino, Laura Cicconi, Alessandro Pulsoni, Michelina Santopietro, Roberto Latagliata, Ambra Di Veroli, Emiliano Fabiani, Martina Quattrone, Flavia Mallegni, Francesca Romana Iovene, Agostino Tafuri","doi":"10.1016/j.leukres.2025.107715","DOIUrl":"10.1016/j.leukres.2025.107715","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"154 ","pages":"Article 107715"},"PeriodicalIF":2.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069757","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
