Higher Graft CD4+ T Cell and B Cell Counts Reduce Relapse Risk in Haploidentical Peripheral Blood Stem Cell Transplantation with Posttransplant Cyclophosphamide

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Introduction Haploidentical hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy) has emerged as a viable option for patients with hematologic malignancies who lack HLA-matched donors. Although several studies have suggested that the composition of lymphocyte subsets in donor grafts might influence post-transplant outcomes, the specific subsets that significantly impact the transplant prognosis remain unclear. Objectives This study aimed to identify the association between specific lymphocyte subsets in donor grafts and posttransplant outcomes in patients undergoing haploidentical peripheral blood stem cell transplantation with PTCy (PTCy-haploPBSCT). Methods We conducted a single-center prospective study involving 57 patients who underwent PTCy-haploPBSCT between 2014 and 2019. Graft composition, including T and B cell subsets , and NK cells , was analyzed using 10-color flow cytometry. Results The median age of the patients and donors at transplantation was 49 years (range: 17-68) and 33 years (range: 12-66), respectively. The diseases included acute myeloid leukemia (n = 29), acute lymphoblastic leukemia (n = 14), myelodysplastic syndrome (n = 9), and others (n = 5). The median CD4+ T cell count was 1.18 × 10⁸/kg (range: 0.21-3.96 × 10⁸/kg), and the median B cell count was 0.42 × 10⁸/kg (range: 0.13-1.50 × 10⁸/kg). After a median follow-up period of 5.8 years, the 3-year cumulative incidence of relapse (CIR) was significantly lower in patients with CD4+ T cell counts above the median (33.0%) compared to those below (65.2%) (Figure A). The 3-year overall survival (OS) rates were 53.1% for patients with CD4+ T cell counts above the median and 34.0% for those below the median, with no statistically significant difference (Figure B). Similarly, the 3-year CIR was significantly lower in patients with B cell counts above the median (24.9%) compared to those with B cell counts below the median (75.6%) (Figure C). Three-year OS was significantly better in patients with B cell counts above the median (59.9% vs. 23.5%) (Figure D). In multivariable analyses adjusted for the hematopoietic cell transplantation comorbidity index and the refined Disease Risk Index, higher CD4+ T cell and B cell counts were significantly associated with a lower risk of relapse, with no significant difference in OS (Table). To explore the mechanism through which CD4+ T cells prevent relapse, we evaluated the proportions of naïve, central memory, and effector memory CD4+ T cells per CD3+ cells. Although no significant differences were found, cases without relapse tended to have a higher proportion of CD4+ central memory T cells in donor grafts. Conclusion Higher graft CD4+ T and B cell counts were associated with a reduced risk of relapse in patients undergoing PTCy-haploPBSCT, suggesting that donor CD4+ T and B cells may enhance anti-tumor immunity.

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