B-Cell Acute Lymphoblastic Leukemia: Donor Matters in Allogeneic Stem Cell Transplant Outcomes of Hispanic Patients

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Hematopoietic stem cell transplantation (HSCT) improves long term overall survival (OS) and disease-free survival (DFS) for intermediate and high-risk B-cell ALL. Historically, matched related donors were the only option, but with better GVHD prophylaxis, haploidentical HSCT (haplo-HSCT) is increasingly used. It may be an option for Hispanic patients for whom donor matching is challenging. This is a retrospective chart review of B-cell ALL patients who received allogeneic HSCT at Norris Comprehensive Cancer Center from 2012 to 2023, excluding mismatched unrelated donors. For OS, DFS, and cumulative incidence of relapse (CIR), matched sibling donors (MSD) and matched unrelated donors (MUD) were grouped. For GVHD outcomes, MSD and MUD were separated. We evaluated incidence outcomes using competing risk regression (Fine-Gray method) with death as a competing outcome. Survival outcomes were analyzed using Cox proportional hazards model. The study included 118 B-cell ALL patients. Median age at transplant was 43 years (range: 21-69). Donor types included 46 (40.0%) MSD, 45 (38.1%) haploidentical, and 27 (22.9%) MUD. Most were Hispanic (N= 92, 78.0%). Median follow-up time was 23.6 months. A majority of patients achieved CR1 (N=79, 66.9%) and MRD negativity by flow (N=106, 89.8%) pre-transplant. The 3-year OS and DFS for the cohort were 82.1% (95% CI 73.8-91.3%) and 66.2% (95% CI 57.2-76.6%), respectively. The CR1 subgroup was 90.5% (95% CI 83.3-98.3%) and 77.1% (95% CI 67.8-87.7%) respectively. Compared to haplo-HSCT, matched donor HSCT had worse CIR (HR = 2.42; 95% CI 1.06-5.51; P = 0.036) and DFS (HR = 2.14; 95% CI 1.03-4.44; P = 0.041). Pretransplant minimal residual disease demonstrated worse OS (HR = 5.01; 95% CI 1.73-14.5; P = 0.003), DFS (HR = 3.25; 95% CI 1.48-7.16; P = 0.003), and CIR (HR = 2.05; 95% CI 0.78-5.39; P = 0.15). The 1-year GRFS, 1-year incidence of severe cGVHD, and 100-day incidence of grade 3-4 aGVHD was 52.6% (95% CI 43.5-63.6%), 29.5% (95% CI 20.9-38.6%), and 7.74% (95% CI 3.79-13.5%), respectively. Compared to haplo-HSCT, GRFS was worse with MUD (HR = 2.07; 95% CI 1.08-3.96; P = 0.028) but similar with MSD. There was no difference in the incidence of severe cGVHD or aGVHD between donor types. Multivariate analysis of age and pretransplant MRD status and disease stage showed improved predictive effect of haplo-HSCT. Matched donors had worse DFS (HR = 2.25; 95% CI 1.04-4.90; P = 0.04) and CIR (HR = 2.47; 95% CI 1.09-5.60; P = 0.03), with a trend towards worse OS (HR = 2.84; 95% CI 0.92-8.79; P = 0.07). Subgroup analysis of the 45 haplo-HSCT controlling for patient age and older donor age analyzed as a continuous variable predicted worse GRFS (HR = 1.05; 95% CI 1.00-1.11; P = 0.039) but did not affect DFS. In a majority Hispanic population of ALL patients, haplo-HSCT demonstrated improved OS and CIR. In haplo-HSCT, younger donor age conferred improved GRFS.

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