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

Publisher: BioMed Central Country of Publication: England NLM ID: 101190723 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7015 (Electronic) Linking ISSN: 17417015 NLM ISO Abbreviation: BMC Med Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2003-

Transplantation Conditioning*/methods ; Histone-Lysine N-Methyltransferase*/genetics ; Myeloid-Lymphoid Leukemia Protein*/genetics ; Decitabine*/therapeutic use ; Decitabine*/administration & dosage ; Hematopoietic Stem Cell Transplantation*/methods; Humans ; Retrospective Studies ; Adult ; Male ; Female ; Middle Aged ; Young Adult ; Adolescent ; China/epidemiology ; Leukemia/therapy ; Transplantation, Homologous/methods ; Gene Rearrangement ; Aged

Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee review board at each participating center and was conducted in accordance with the principles of the Declaration of Helsinki. The reference number for the ethics committee was NFEC-2009–23. Written informed consent was obtained from all the patients. Consent for publication: All of the authors agreed to submit and publish the final manuscript. Competing interests: The authors declare no competing interests.
Background: 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.
Methods: 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 ² /day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m ² /day on days -10 to -6; the same dose of TBI-Cy).
Results: 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.
Conclusions: 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.
(© 2024. The Author(s).)

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82293634 National Natural Science Foundation of China; 82170213 National Natural Science Foundation of China; 2021YFC2500300-4 National Key Research and Development Program of China; 2022YFC2502600-5 National Key Research and Development Program of China; 2024A1515010794 Natural Science Foundation of Guangdong Province

Keywords: Allo-HSCT; Decitabine; Intensified conditioning; KMT2A-r leukemia

EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
0 (KMT2A protein, human)
776B62CQ27 (Decitabine)

Date Created: 20241230 Date Completed: 20241231 Latest Revision: 20250104

20250114

PMC11687046

10.1186/s12916-024-03830-0

39736728