According to the results of a study published in Bone Marrow Transplantation, patients with acute myeloid leukemia (AML) undergoing transplantation from a haploidentical donor in first remission (CR1) who received 2 induction courses had a nearly 2-fold higher 2-year relapse incidence (RI) and significantly inferior leukemia-free survival (LFS), overall survival (OS), and graft vs host disease (GVHD)-free, relapse-free survival (GRFS) compared with patients who achieved CR after only 1 course of chemotherapy. The findings suggest that these patients may benefit from additional novel therapies in the conditioning regimen or post-transplant stage.
The investigators conducted the retrospective study using the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) registry dataset. They compared transplantation outcomes of adults with AML that underwent haploidentical stem cell transplantation (HaploSCT) in CR1 achieved following 1 or 2 induction chemotherapy courses.
A total of 635 patients, 469 (74%) with 1 and 166 (26%) with 2 induction chemotherapy courses, were included in the study. The median patient age was 45.3 (range, 18-75) and 45.8 (18.3-72.2) years in 1 and 2 induction groups, respectively. In both groups, approximately 91% of patients had de novo AML. Most baseline demographics and clinical characteristics were similar between the groups, except time from diagnosis to CR1 (1 and 2 induction groups, 35 and 70.5 days; P <.001), carriers of the FMS-like tyrosine kinase 3 (FLT3) mutation (24.5% and 15.9%; P =.046), and nucleophosmin-1 (NPM1)-positive status (21.1 and 6.4%; P =.0002).
The median year of the HaploSCT was 2015 (range, 2006-2019), and the median follow-up duration from transplant was 30.8 months (interquartile range, 27.4-33.6). Engraftment rates were 97.2 and 97.6% in the 1 and 2 induction groups, respectively. Both groups had similar Day 180 incidence of acute GVHD II-IV (1 and 2 induction groups, 31.1% and 34.8%) and III-IV (10% and 10.6%) and 2-4 year total (33.7% and 36.5%) and extensive chronic GVHD (12.2% and 12.1%). Patients who achieved CR1 with 2 inductions had a significantly higher 2-year RI (29.1% vs 15.1%; P =.001) and significantly lower LFS (56.2% vs 66.9%; P =.03), OS (58.8% vs 72.2%; P =.044) and GRFS (44% vs 55.6%; P =.013) than those who achieved CR with 1 induction course. The groups did not differ in nonrelapse mortality. The investigators confirmed the findings with multivariate analysis.
Limitations of the study included the possible confounding variables and unavailable or unconsidered data, such as missing molecular and measurable residual disease data and complete blood counts, lack of pre-transplantation data, and applicability to only patients with AML receiving traditional 7 + 3 induction.
Nagler A, Labopin M, Huang XJ, et al. Non-T depleted haploidentical stem cell transplantation in AML patients achieving first complete remission after one versus two induction courses: a study from the ALWP/EBMT. Bone Marrow Transplant. Published online February 1, 2022. doi:10.1038/s41409-021-01537-x