Effect of Donor Characteristics on T Cell Replete Haploidentical Stem Cell Transplantation: Over the Last 10 Years at a Single Institution

Background: Owing in part to the development of T-cell-replete strategies such as PTCy based graft versus host disease (GVHD) prophylaxis, colony-stimulating factor (G-CSF), and anti-thymocyte globulin (ATG) approach, it increases donor availability for almost all patients in need, which was associated with survival outcomes comparable to those of human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation (HSCT). So there has been a rapid expansion in Haploidentical stem cell transplantation (haplo-SCT). One of the most complex issues with haplo-SCT is donor selection, given that multiple haploidentical donors are often available for a given recipient.

Methods: To develop evidence-based guidance for donor selection in the setting of ATG-based T-cell-replete haplo-SCT, we performed a prospective cohort study of 512 consecutive hematologic malignancies patients accepting haplo-SCTs at a single center to determine which donor variables were most important in favoring transplant outcomes when applied in the uniform G-CSF mobilized peripheral blood stem cell (PBSC) source, myeloablative conditioning regimen, and low-dose ATG based GVHD prophylaxis.

Results: In our low dosage ATG based T-cell replete Haplo-SCT and PBSC donor source protocol, increasing donor age was the only donor characteristic that influenced overall survival (OS). Donor age increasing by five years was associated with poorer OS (HR, 1.08 [1.00, 1.17; P =0.044]). Female donor to the male recipient, ABO incompatibility, increasing patient age, and HLA genotype did not influence OS in multivariable analyses. Female donor to the male recipient was significantly associated with higher non-relapse mortality (NRM) (HR, 2.05 [1.23, 3.41; P =0.006]). Increasing donor age by five years had the trend of higher NRM (HR, 1.11 [0.98, 1.25; P =0.094]). ABO incompatibility, increasing patient age, HLA genotype, disease, disease risk index (DRI) did not impact NRM. No donor-related variables had a significant influence on Relapse. Besides, increasing donor age (per 5 yr) had a higher risk for grade 3 to 4 acute GVHD (aGVHD) (HR, 1.17 [1.05, 1.30; P= 0.005]), female donor to the male recipient was associated with higher risk for grade 2 to 4 aGVHD (HR, 1.50 [1.06, 2.11; P= 0.022]). Sibling donors had superior OS(79.3% vs 63.8%, P=0.003), Disease-free survival (DFS) (76.9% vs 62.2%, P=0.009), and NRM (5.1% vs 13.8%, P=0.048) than parental donors in the group of patients age <35. However, sibling donors had higher NRM (32.4% vs. 11.1%, P=0.008) than offspring donors in the group of patients age ³35. Maternal donors appeared higher risk of developing cumulative incidence of 100-day grade 2 to 4 aGVHD than paternal donors (HR, 1.95 [1.25, 3.03; P= 0.003]). But no significant differences of OS, DFS, NRM, Relapse, 3 to 4 aGVHD, and chronic GVHD (cGVHD) were observed between maternal and paternal donors.

Conclusion: We found that younger donors were associated with superior OS, lower NRM and lower risk for the cumulative incidence of grade 3 to 4 aGVHD, a female donor to a male recipient was associated with higher NRM and higher risk for the cumulative incidence of grade 2 to 4 aGVHD, sibling donors had superior outcomes than parental donors in younger recipients (yr<35), whereas offspring donors had superior results than sibling donors in older recipients (yr³35). Paternal donors are preferred than maternal donors. ABO incompatibility didn't affect transplant outcomes as PBSC derived grafts used. These data strongly suggest that a younger donor, usually a young sibling or a young offspring, generally avoid female donor to a male recipient, should be preferred when multiple haplo donors are available.