Factors associated with outcomes following reduced intensity conditioning haploidentical hematopoietic cell transplantation in acute myeloid leukemia.

Abstract

6560 Background: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for high-risk acute myeloid leukemia (AML). Elderly patients can undergo HCT using a reduced-intensity conditioning (RIC) regimen. When HLA-matched donors are unavailable, haploidentical (Haplo) family donors can be used, offering outcomes similar to those with matched donors. This study investigates factors influencing outcomes following RIC haplo HCT with posttransplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis. Methods: A retrospective multicenter study was conducted using the CIBMTR registry (2012-2017, P-5737 dataset, Ustun et al.) to assess AML patients undergoing first RIC haplo-HCT. Outcomes included overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic GVHD, GVHD-free relapse-free survival (GRFS), and engraftment. Patient- and transplant-related factors were analyzed with Chi-square and Wilcoxon tests. Kaplan-Meier and univariate and multivariate Cox regression analyses were conducted. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Statistical significance was defined as p<0.05. Results: We included 185 AML patients undergoing the first RIC haplo-HCT with PT-Cy-based GVHD prophylaxis. The median age was 63.8 years, 58% were male, and 70% were Caucasians. Graft sources were peripheral blood (55%) and bone marrow (45%), with a graft cell dose of>2 million CD34 cells/kg in 82% of patients. HCT-Comorbidity index (CI) was three or higher in 45% of patients, and Karnofsky's performance status was <90% in 53% of patients. The median follow-up was 4 years, and 36% were alive at the last follow-up. The median OS, DFS, and GRFS were 1.59, 0.76, and 0.31 years, respectively. Primary disease (33.5%), organ failure (9%), and infection (8%) were the leading causes of death. Relapse, acute (grade II-IV), chronic GVHD, and NRM occurred in 52%, 36%, 30%, and 20.5% of patients, respectively. Neutrophil engraftment occurred over a median of 17 days. In multivariate analyses, high disease risk independently predicted inferior OS (HR 1.72, p=0.012), inferior DFS (HR 1.49, p=0.136), higher relapse (HR 1.88, p=0.028), and higher NRM (HR 2.12, p=0.011). Higher HCT-CI predicted inferior OS (HR 1.88, p=0.041), higher NRM (HR 5.21, p=0.043), and delayed neutrophil engraftment (HR 0.37, p<0.001). Asians, compared to Caucasians, had superior GRFS (HR 0.46, p=0.040). Conclusions: In AML patients undergoing RIC haploidentical HCT, favorable outcomes were observed, and key determinants were high disease risk and comorbidities. Relapse remains the leading cause of treatment failure. These findings suggest pre-transplant assessments and post-transplant strategies to mitigate relapse risk for optimizing outcomes in this patient population.