Intensified conditioning containing decitabine versus standard myeloablative conditioning for adult patients with KMT2A-rearranged leukemia: a multicenter retrospective study

• Published in: BMC medicine Vol. 22; no. 1; pp. 605 - 11
• Main Authors: Hu, Zhongli, Feng, Zinan, Liu, Shiqi, He, Hai, Dong, Ying, Fan, Zhiping, Li, Yiqing, Huang, Fen, Xu, Na, Liu, Can, Zeng, Yunxin, Zhu, Ping, Lin, Ren, Jin, Hua, Zhang, Xiong, Sun, Ruijuan, Liu, Qifa, Xuan, Li
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.12.2024; BioMed Central; BMC
• Subjects: 5-aza-2'-deoxycytidine; Acute leukemia; Adolescent; Adult; Aged; Allo-HSCT; Allografts; Blood; Blood platelets; Bone marrow; Busulfan; Cancer; Care and treatment; China - epidemiology; Conditioning; Cyclophosphamide; Cytogenetics; Decitabine; Decitabine - administration & dosage; Decitabine - therapeutic use; Disease prevention; Female; Gene Rearrangement; Graft versus host disease; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Histone-Lysine N-Methyltransferase - genetics; Humans; Intensified conditioning; Irradiation; KMT2A-r leukemia; Leukemia; Leukemia - therapy; Male; Medical diagnosis; Medical prognosis; Middle Aged; Myeloid-Lymphoid Leukemia Protein - genetics; Neutrophils; Patient outcomes; Patients; Relapse; Remission (Medicine); Retrospective Studies; Stem cell transplantation; Stem cells; Subgroups; Survival; Toxicity; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous - methods; Transplants & implants; Young Adult; China; Decitabine; Intensified conditioning; Allo-HSCT; KMT2A-r leukemia
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-024-03830-0

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia. We performed a multicenter retrospective study at seven institutions in China. Eligible patients were aged 14 years or older at transplantation, had a diagnosis of KMT2A-r leukemia, and underwent the first allo-HSCT. Standard myeloablative conditioning regimens (standard group) included BuCy (busulfan 3.2 mg/kg/day on days -7 to -4; cyclophosphamide 60 mg/kg/day on days -3 to -2) and TBI-Cy (total body irradiation 4.5 Gy/day on days -5 to -4; Cy 60 mg/kg/day on days -3 to -2). Intensified conditioning regimens containing Dec (intensified group) consisted of Dec-BuCy (Dec 20 mg/m /day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m /day on days -10 to -6; the same dose of TBI-Cy). Between April 2009 and December 2019, 218 patients were included in this study, of whom 105 were in the intensified group and 113 were in the standard group. The 3-year cumulative incidence of relapse was 17.6% and 34.5%, overall survival was 71.3% and 61.0%, disease-free survival was 70.1% and 56.0%, and non-relapse mortality was 12.3% and 9.5% in the intensified and standard groups, respectively (P = 0.001; P = 0.034; P = 0.005; P = 0.629). Subgroup analysis showed that the relapse rate of intensified conditioning was lower than that of standard conditioning in multiple subgroups, including different leukemia types, disease status at transplantation, high-risk cytogenetics and Bu-based regimens. There was no difference in regimen-related toxicity, engraftment, or graft-versus-host disease between the intensified and standard groups. These results suggest that intensified conditioning containing Dec might be a better strategy than standard myeloablative conditioning for adult patients with KMT2A-r leukemia undergoing allo-HSCT.