OUTCOMES OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ACUTE MYELOID LEUKEMIA PATIENTS WITH ACTIVE REFRACTORY DISEASE BEFORE TRANSPLANT

Abstract

Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is the most potent post-remission treatment for Acute Myeloid Leukemia (AML) to reduce relapse rates. However, achieving Complete Remission (CR) and Minimal Residual Disease (MRD) before transplant are crucial predictors of relapse and mortality post-consolidation therapy. This study aims to describe the characteristics and outcomes of AML patients who underwent HSCT without achieving CR. Methods: We conducted a retrospective analysis of AML patients with active refractory disease who underwent HSCT between 2010 and 2024 at two Brazilian centers. Active AML was defined as having more than 5% blasts in the Bone Marrow (BM) before starting conditioning or a sequential conditioning regimen. Results: A total of 28 AML patients with refractory disease after multiple lines of therapy (including a prior HSCT in 5 patients) were included. The median age was 47 years (range, 19‒83), 39% were male, and the median percentage of blasts in BM at the start of HSCT was 11% (range: 5%‒50%). Nine out of 19 assessed patients (47%) were high-risk based on the HCT-CI score. Donors were haploidentical in 15 patients (53.6%), matched unrelated in 7 patients (25%), and matched related in 6 patients (21.4%). Reduced-Intensity Conditioning (RIC) was performed in 22 patients (79%), with FluCyTBI 2 or 4 Gy in 16 patients (73%), FluBu6.4 in 5 patients (23%), and FluMel140 in 1 patient (4%). Myeloablative Conditioning (MAC) was used in 6 patients (21%), with FluBu9.6 in 3 patients (50%), BuCy in 2 patients (33%), and FluTBI12Gy in 1 patient (17%). Mobilized peripheral blood stem cells were the most common stem cell source (21 patients, 75%), while bone marrow was used in 7 patients (25%). The cumulative incidence (CI) of relapse/progression at 3-months, and 3-years was 18%, and 36%, respectively. The CI of non-relapse mortality (NRM) at 3-months, and 3-years was 14% and 26%, respectively. The CI of acute grade II‒IV GVHD at 100-days was 21%, and the CI of chronic GVHD at 3-years was 29%, with only patients requiring prolonged systemic therapy. After a median follow-up of 42-months, Overall Survival (OS) and Progression-Free Survival (PFS) at 3-years were 42% and 44%, respectively. The blast count in BM immediately before HSCT was a strong predictor of survival: OS at 3-years was 22% compared to 76% for patients with 10% or fewer blasts (p = 0.015), and PFS was 22% vs. 65% (p = 0.035). Conclusion: HSCT is a feasible and safe alternative for patients with refractory or relapsed AML after multiple lines of therapy, particularly for those with 10% or fewer blasts in BM before transplant. However, prospective studies with larger cohorts are needed to further define the role of HSCT in this challenging context.