Analysis of the Impact of Donor Characteristics on Outcomes after 2-Step Haploidentical (HI) Hematopoietic Stem Cell Transplantation (HSCT) (2017)

Background: HI HSCT affords donor selection opportunities based on non-MHC characteristics. No standard method for HI HSCT donor selection exists in part because optimal donor characteristics may vary based on the treatment approach. After conditioning in our 2-step HI HSCT approach, a fixed T-cell dose (2 × 108/kg) is administered, followed 2-3 days later by cyclophosphamide (CY) for tolerization. Two days after CY, patients receive a CD 34-selected donor product. We analyzed the impact of non-MHC donor characteristics on outcomes after 2-step HI-HSCT. Methods: This is a retrospective analysis of 180 patients with hematologic malignancies undergoing HI HSCT between 2006 and 2016. The impact of donor characteristics (KIR 2DS2, -B haplotype, age), and donor recipient combinations (KIR ligand mismatch, female into male, offspring into mother, and CMV status) on the primary end points of relapse and acute GVHD grades II-IV and secondary endpoints of overall survival (OS), non-relapse mortality (NRM) and chronic GVHD were examined. Recipient age, HCT-CI and RDRI were included as confounders. Competing risk analyses were used to estimate the probabilities of relapse, NRM, aGVHD and cGVHD. Probability of OS was estimated by Kaplan-Meier method and multivariable analyses using Cox proportional hazards. A subset analysis of patients with AML and MDS (n = 103) was performed to assess natural killer cell alloreactivity specific to this population. Results: Median follow up was 16.8 (range: .4-118) months. In the overall sample KIR-B haplotype donors were associated with higher aGVHD grades II-IV (HR = 1.78; P = .03). Relapse incidence was significantly higher in offspring-to-maternal transplantation both in overall (HR = 2.01; P = .04) and myeloid samples (HR = 2.44; P = .046) but in this analysis, was not influenced by KIR ligand mismatch or the presence of activating KIR in donor. In the overall sample, donor age < 42 years (HR = .51; P = .01) was associated with improved OS. Donors expressing KIR 2DS2 resulted in improved OS (HR = .56; P = .047) and lower NRM (HR = .36; P = .018) in the myeloid group. Female-to-male transplantation was associated with higher NRM in the overall sample (HR = 2.21; P = .019) and higher NRM (HR = 3.46; P = .008) and cGVHD (HR = 3.53; P = .017) in the myeloid subset. Discussion: For recipients undergoing HI HSCT on the 2-step approach, this analysis supports the avoidance of offspring donors for maternal recipients due to an increased hazard of relapse, and the avoidance of female donors for male recipients. KIR-B haplotype donors were associated with alloreactivity in the form of aGVHD, but the specific use of KIR 2DS2 donors may be beneficial in myeloid malignancies to decrease NRM and increase OS. Younger donors should be favored over their older counterparts. We will continue to study the impact of these characteristics to help inform donor selection as our population grows.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)