Hematopoietic cell transplantation in acute lymphoplastic leukemia: The Mexican experience

Abstract

Abstract INTRODUCTION Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for high-risk and relapsed/refractory acute lymphoblastic leukemia (ALL), particularly in settings where there is no access to novel immunotherapies. In this multicenter national study, we aimed to describe a contemporary cohort of Mexican ALL patients who underwent HCT, including their characteristics and outcomes. PATIENTS AND METHODS This was a retrospective multicenter analysis of adult and pediatric ALL patients who underwent an allogeneic HCT between 2022 and 2025 across public and private transplant centers in Mexico, performed on behalf of the national adult and pediatric transplant societies. All transplant centers were invited to participate and submit patient-level data on pre- and post-transplant characteristics. The primary outcome was 2-year overall survival (OS). Secondary outcomes included graft-versus-host disease (GVHD) incidence and severity, non-relapse normality (NRM), cumulative incidence of relapse (CIR) and disease-free survival (DFS). Multivariable Cox regression analyses were conducted and included variables with p < 0.1 in the univariate analysis. RESULTS A total of 264 patients from 7 centers were included. The median age was 19 years (range, 1-65), and 64.8% were males. The predominant phenotype was B-cell precursor ALL in 90.5%; in these, BCR/ABL was present in 19.7%. CNS infiltration was present in 11.8% of patients, and 25.8% of patients had been exposed to blinatumomab. Most patients had good performance status and no comorbidities. The median number of previous treatment lines was 2 (range, 1-8). HCT was performed in first complete remission (CR1) in 20.8% of patients, in second remission or beyond (CR2+) in 72.3%, and in refractory disease in 6.8%. Measurable residual disease was positive before HCT in 13.9 A chemotherapy-based myeloablative conditioning (MAC) regimen was administered in 51.9% of patients, while total body irradiation (TBI)-based conditioning was used in 9.8%. Median CD34+ cell administered was 8.6 X 106/kg. Peripheral blood was the stem cell source in all cases. HCT donors were from haploidentical donors in 75.3%, compared to 26.1% from matched related donors, with a single matched unrelated donor. The median age of donors was 30 years, 64% were males, and their relationship to patients was sibling in 54.9%, parent in 40.2%, and an offspring in 3.8%. The median time to neutrophil and platelet engraftment was 14 days (IQR, 13.0-16.3), and 15 days (IQR, 13.0-18.0), respectively. Primary graft failure occurred in 6.8%. The median follow-up was 25 months. Grade II-IV acute graft versus host disease (GVHD) had an incidence of 30.6 (95% CI, 24.8-36.6), whereas the 2-year overall incidence of moderate or severe chronic GVHD was 23.7% (95% CI, 18.3-29.5). The 24-month OS and DFS were 56.2% (95% CI, 49.1-62.7) and 43.4% (95% CI, 36.6-50.1), respectively. The 2-year overall cumulative incidences of relapse and non-relapse mortality (NRM) were 41.7% (95% CI, 35.0-48.3) and 14.8% (95% CI, 10.6-19.8), respectively. In the multivariable analysis for OS, significant predictors were CR2+ status (HR 1.651, 95% CI, 1.133-2.407; p=0.009) and chemotherapy-based MAC (HR 1.601, 95% CI, 1.085-2.362; p=0.018). For DFS, only CR2+ status was significant on multivariable analysis (HR 1.746, 95% CI, 1.245-2.449; p=0.001). Twenty-three patients (8.7%) underwent a second HCT.CONCLUSIONS: HCT in ALL patients constitutes an ongoing therapeutic challenge. Despite recent advancements, cooperation and support between different transplant centers is crucial to a better characterization of ALL in resource- limited settings, as it assists in improving outcomes for survival, complications and quality of life.