Leukemia researchPub Date : 2025-09-13DOI: 10.1016/j.leukres.2025.108099
Doudou Chang , Linhua Yang , Ruijuan Zhang
{"title":"Pathogenic mechanisms and targeted therapies for anemia in myelodysplastic syndromes","authors":"Doudou Chang , Linhua Yang , Ruijuan Zhang","doi":"10.1016/j.leukres.2025.108099","DOIUrl":"10.1016/j.leukres.2025.108099","url":null,"abstract":"<div><div>Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS(including low-risk MDS and high-risk MDS), covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108099"},"PeriodicalIF":2.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145098913","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 : 2025-09-05DOI: 10.1016/j.leukres.2025.108089
Ehab L. Atallah , Islam Sadek , David Wei , Dominick Latremouille-Viau , Carmine Rossi , Andrea Damon , Daisy Yang , Remi Bellefleur , Annie Guérin , Kejal Jadhav
{"title":"Treatment with asciminib after a prior tyrosine kinase inhibitor in patients with chronic-phase chronic myeloid leukemia","authors":"Ehab L. Atallah , Islam Sadek , David Wei , Dominick Latremouille-Viau , Carmine Rossi , Andrea Damon , Daisy Yang , Remi Bellefleur , Annie Guérin , Kejal Jadhav","doi":"10.1016/j.leukres.2025.108089","DOIUrl":"10.1016/j.leukres.2025.108089","url":null,"abstract":"<div><h3>Background</h3><div>In chronic-phase chronic myeloid leukemia (CML-CP), switching tyrosine kinase inhibitor (TKI) therapy due to intolerance or resistance is common. While asciminib, an ABL/BCR::ABL1 TKI targeting the ABL myristoyl pocket, offers improved tolerability and efficacy, there is limited real-world effectiveness data, particularly among patients with treatment with one prior TKI.</div></div><div><h3>Patients and methods</h3><div>A retrospective, US physician panel-based chart review study was conducted on adult patients with CML-CP without T315I treated with asciminib after one prior TKI. Time-on-treatment, and time-to achieving or maintaining MR2 (BCR::ABL1 ≤ 1 %), MMR (BCR::ABL1 ≤ 0.1 %) and DMR (BCR::ABL1 ≤ 0.01 %) were assessed using Kaplan-Meier analyses. Subgroup analyses were performed among patients with first TKI discontinuation due to intolerance or resistance, and by first- or second-generation TKI as first TKI.</div></div><div><h3>Results</h3><div>Overall, 255 patients (median age 62 years, 56.5 % male) were included. Imatinib (49.8 %), dasatinib (34.5 %), nilotinib (10.6 %), and bosutinib (5.1 %) were received as first TKI. Intolerance and resistance to first TKIs were reported for 43.5 % and 23.5 % of patients, respectively. At 48-weeks post-asciminib initiation, 95.0 % of patients (95 % CI: 91.3 %, 97.1 %) remained on asciminib, 84.0 % (95 % CI: 78.6 %, 88.6 %) achieved or maintained MR2, 68.3 % (95 % CI: 61.8 %, 74.5 %) MMR, and 40.6 % (95 % CI: 34.2 %, 47.8 %) DMR.</div></div><div><h3>Conclusions</h3><div>Overall, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well-tolerated and effective. Results were consistent among subgroups, indicating that asciminib is an effective option for patients regardless of prior TKI used, and including those intolerant or resistant to their first TKI.</div></div><div><h3>Micro-abstract</h3><div>There is limited real-world data regarding the effectiveness of asciminib after one prior tyrosine kinase inhibitor (TKI) in chronic-phase chronic myeloid leukemia (CML-CP). In this US physician panel-based chart review, nearly all patients (95 %) remained on asciminib and 68 % achieved or maintained a major molecular response at 48 weeks, suggesting that asciminib is well-tolerated and effective after one prior TKI.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"157 ","pages":"Article 108089"},"PeriodicalIF":2.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054377","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 : 2025-09-04DOI: 10.1016/j.leukres.2025.108098
J. Preston Claiborne , Daniel Li , Hua-Ling Tsai , Gabriel Ghiaur , B. Douglas Smith , Mark J. Levis , Amy E. DeZern , Alex J. Ambinder , Tania Jain , Gabrielle T. Prince , Lukasz P. Gondek , Theodoros Karantanos , W. Brian Dalton , Ivana Gojo , Jonathan A. Webster
{"title":"Efficacy and safety of blinatumomab for CD19 + acute leukemias in patients historically excluded from clinical trials due to comorbidities","authors":"J. Preston Claiborne , Daniel Li , Hua-Ling Tsai , Gabriel Ghiaur , B. Douglas Smith , Mark J. Levis , Amy E. DeZern , Alex J. Ambinder , Tania Jain , Gabrielle T. Prince , Lukasz P. Gondek , Theodoros Karantanos , W. Brian Dalton , Ivana Gojo , Jonathan A. Webster","doi":"10.1016/j.leukres.2025.108098","DOIUrl":"10.1016/j.leukres.2025.108098","url":null,"abstract":"<div><h3>Background</h3><div>Blinatumomab has proven efficacy in the frontline, consolidation, and relapsed/refractory settings in B cell acute lymphoblastic leukemia. Its efficacy and safety among patients commonly excluded from clinical trials are unknown.</div></div><div><h3>Patients and Methods</h3><div>This single center, retrospective cohort study included patients treated for acute leukemia with blinatumomab with the following pre-existing conditions: liver dysfunction, renal impairment, central nervous system (CNS) conditions, autoimmune disease, solid organ transplantation, or uncontrolled infection. Rates of blinatumomab completion, efficacy outcomes, cytokine release syndrome (CRS), neurotoxicity (ICANS), and adverse events specific to the impaired organ leading to inclusion were assessed.</div></div><div><h3>Results</h3><div>Thirty-four patients were included, and 88 % completed at least one cycle of blinatumomab. One patient stopped prematurely due to toxicity and three due to lack of response in the relapsed/refractory setting. Response rates and survival were similar by treatment setting to those treated in clinical trials. The 60-day cumulative incidence of grade ≥ 2 CRS and ICANS were 23.5 % and 20.8 %, respectively. No excess liver injury, ICANS, autoimmune flares, organ rejection, or infections were observed in cohorts defined by impairment of each system.</div></div><div><h3>Conclusion</h3><div>Blinatumomab was successfully administered to the vast majority of patients with a baseline condition that would have led to clinical trial exclusion. Adverse events generally occurred at rates similar to prior clinical trials. These data provide the basis to consider removing certain exclusion criteria from future studies involving blinatumomab, allowing more patients to benefit from its efficacy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"157 ","pages":"Article 108098"},"PeriodicalIF":2.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080943","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 : 2025-09-01DOI: 10.1016/j.leukres.2025.107988
Yang Fu, Ling Jin, Yanlong Duan, Jing Yang, Ying Liu, Bo Hu, Mincui Zheng, Yunpeng Dai, Ansheng Liu, Wei Liu, Leping Zhang, Fu Li, Baoxi Zhang, Xiaojun Yuan, Lirong Sun, Rong Liu, Zhuoyu Wen, Runming Jin, Shuquan Zhuang, Lian Jiang, Xiaowen Zhai
{"title":"CLINICAL CHARACTERISTICS AND TREATMENT EVALUATION OF DIFFUSE LARGE B-CELL LYMPHOMA IN CHINESE CHILDREN AND ADOLESCENTS: A MULTICENTER CLINICAL STUDY OF CHINA-NET CHILDHOOD LYMPHOMA GROUP B-NHL-2017","authors":"Yang Fu, Ling Jin, Yanlong Duan, Jing Yang, Ying Liu, Bo Hu, Mincui Zheng, Yunpeng Dai, Ansheng Liu, Wei Liu, Leping Zhang, Fu Li, Baoxi Zhang, Xiaojun Yuan, Lirong Sun, Rong Liu, Zhuoyu Wen, Runming Jin, Shuquan Zhuang, Lian Jiang, Xiaowen Zhai","doi":"10.1016/j.leukres.2025.107988","DOIUrl":"10.1016/j.leukres.2025.107988","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925031","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 : 2025-09-01DOI: 10.1016/j.leukres.2025.107960
Jacques Cornwell, Christopher Steel, Dawid Przystupski, Rogier ten Hoopen, Jamie D. Matthews, Lucy Hare, Nina Prokoph, G. A. Amos Burke, Suzanne D. Turner
{"title":"INVESTIGATING KINASE DEPENDENCIES IN ALK+ALCL","authors":"Jacques Cornwell, Christopher Steel, Dawid Przystupski, Rogier ten Hoopen, Jamie D. Matthews, Lucy Hare, Nina Prokoph, G. A. Amos Burke, Suzanne D. Turner","doi":"10.1016/j.leukres.2025.107960","DOIUrl":"10.1016/j.leukres.2025.107960","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925144","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 : 2025-09-01DOI: 10.1016/j.leukres.2025.108023
Kai Wang, Ying Liu, Yang Liu, Pei Zhang, Qiyu Yang, Guomin Wang, Yali Peng, Yonghong Zhang
{"title":"EFFECTIVENESS OF ALK INHIBITOR COMBINED WITH VINBLASTINE IN THE TREATMENT OF RELAPSED REFRACTORY CHILDHOOD ALK+ ANAPLASTIC LARGE CELL LYMPHOMA","authors":"Kai Wang, Ying Liu, Yang Liu, Pei Zhang, Qiyu Yang, Guomin Wang, Yali Peng, Yonghong Zhang","doi":"10.1016/j.leukres.2025.108023","DOIUrl":"10.1016/j.leukres.2025.108023","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925365","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":"SURVIVAL OUTCOMES IN ADOLESCENT HODGKIN AND NON-HOODGKIN LYMPHOMAS: A RETROSPECTIVE STUDY AT A TERTIARY CARE CENTRE IN NORTH EASTERN INDIA","authors":"Chandra Mohan Kumar, Tulasiram Nalam, Arnab Ghorui, Gurleen Kaur Kalra","doi":"10.1016/j.leukres.2025.107974","DOIUrl":"10.1016/j.leukres.2025.107974","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925624","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 : 2025-09-01DOI: 10.1016/j.leukres.2025.107760
Moshe Mittelman
{"title":"COLLABORATIVE DEBATE SESSION: THERAPEUTIC AGENTS IN MYELODYSPLASTIC SYNDROMES – TOO FEW AND NOT EFFECTIVE ENOUGH: WE CAN DO BETTER","authors":"Moshe Mittelman","doi":"10.1016/j.leukres.2025.107760","DOIUrl":"10.1016/j.leukres.2025.107760","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107760"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059845","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}