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Impact on outcome of MRD prior hematopoietic stem cell transplantation after FLAMSA-busulfan conditioning regimen: a retrospective monocentric study
Meur, G. L., Plesa, A., Larcher, M. V., Fossard, G., Barraco, F., Loron, S., Balsat, M., Ducastelle-Lepretre, S., Gilis, L., Thomas, X., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) conditioned by sequential association of fludarabine, amsacrine, cytosine arabinoside (FLAMSA) followed by a reduced intensity conditioning regimen emerged for patients with high-risk acute myeloid leukemia (AML), especially in refractory or relapsing patients. OBJECTIVE We aimed to address retrospectively the impact of pre-transplant minimal residual disease (MRD) by flow cytometry (FCM) on outcome of high-risk AML patients who underwent allo-HSCT after sequential FLAMSA-Busulfan (FLAMSA-BU) based conditioning regimens. STUDY DESIGN We included 165 high-risk AML patients transplanted after FLAMSA-BU in this retrospective one-center "real life" study. All patients received in vivo T-cell depletion using anti-thymocyte globuline (5 mg/kg). MRD detection was based on leukemia associated immunophenotype (LAIP) using the ELN recommendations, with a threshold of 0.1%. Univariate and multivariate analysis were performed using R software version 4.1.1. RESULTS With a median follow-up of 4.0 years post-transplant, median overall survival (OS) was 54.9 months. Overall, 41 patients (24.8%) relapsed post-transplant with a resulting cumulative incidence of relapse (CIR) at 2 and 5 years of 26.7% and 34.0% respectively. Detectable MRD preceding allo-HSCT, as refractory status, were both associated with worse median OS and CIR rates compared to patients without detectable MRD. However, OS was not significantly different between pre-HSCT MRD+ and refractory patients (median 0.7 vs 2.0 years, p=0.3). Conversely, pre-HSCT MRD negativity was associated with a reduced 2-year cumulative incidence of relapse (CIR). Neither European LeukemiaNet (ELN) risk stratification nor age did significantly influence OS. In the multivariate analysis, only pre-HSCT MRD positivity and lower conditioning regimen intensity were significantly associated with a poorer OS. Cumulative incidence of extensive chronic graft versus host disease (cGVHD) at 2 years was 26.15%. Estimated non-relapse mortality (NRM) of the entire cohort at 2 years was 23.1%, with age and unrelated donor as risk factors of higher NRM. CONCLUSION FLAMSA-Busulfan did not reverse the pejorative effect of detectable pre-HSCT MRD, suggesting that such patients should be offered alternative strategies prior HSCT to reach deeper remission.