Intensified Conditioning Containing Decitabine Versus Standard Myeloablative Conditioning for Adult Patients with KMT2A-Rearranged Leukemia: A Multicenter Retrospective Study

Background: KMT2A-rearranged (KMT2A-r) leukemia has a poor prognosis. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is recommended for patients with this disease, but relapse remains high. In addition to disease-associated factors, intensities of conditioning are an essential factor affecting relapse post-transplantation. 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 six institutions in China. Eligible patients were aged 14 years or older at transplantation, had a diagnosis of KMT2A-r leukemia, and underwent 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; cyclophosphamide 60 mg/kg/day on days -3 to -2). Intensified conditioning regimens containing Dec (intensified group) consisted of Dec-BuCy (Dec 20 mg/m2/day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m2/day on days -10 to -6; the same dose of TBI-Cy).

Results: Between April 2009 and December 2019, 218 patients were enrolled including 105 in the intensified group and 113 in the standard group. The 3-year cumulative incidence of relapse was 19.4% and 37.0%, overall survival was 71.3% and 61.0%, disease-free survival was 70.1% and 56.0%, and non-relapse mortality was 13.0% and 11.1% in the intensified and standard groups, respectively (P = 0.001; P = 0.034; P = 0.005; P = 0.850). Subgroup analysis showed the relapse rate of intensified conditioning was lower than that of standard conditioning in multiple subgroups, including different leukemia types and disease status at transplantation, high-risk cytogenetics and busulfan-based regimens. Grade 3 or worse RRT occurred in 11 (10.5%) and 10 (8.8%) patients in the intensified and standard groups, respectively. One (1.0%) patient in the intensified group died of heart toxicity, and one (0.9%) in the standard group died of kidney toxicity. There was no difference in 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, which requires further confirmation in prospective, randomized controlled studies.