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OBJECTIVES/GOALS: Patients who require a hematopoietic cell transplant (HCT) and dont have an HLA-matched related or unrelated donor may rely on a haploidentical donor. The optimal haploidentical donor and guidance for selection is limited. We aim to determine how donor characteristics affect outcomes following haploidentical-HCT for pediatric patients. METHODS/STUDY POPULATION: This is a retrospective cohort study evaluating the effect of donor age and relationship on post-HCT outcomes in children (0-18y) from 2008-2018. Multivariable logistic regression analysis will identify if donor age or donor relationship affect the development of graft-versus-host-disease (GVHD), while adjusting for other patient, donor, and transplant related variables. Two-year overall survival & event-free survival will be determined using Kaplan-Meier curves, stratified by donor age group and donor relationship, and compared by log-rank testing. Sub-analyses will be performed for myeloablative transplants and reduced intensity conditioning, as well as for malignant and non-malignant diseases. RESULTS/ANTICIPATED RESULTS: Our primary aim to is determine the effect of donor age and the effect of donor relationship to patient on the development of GVHD. We hypothesize that utilization of a younger donor will decrease the incidence of GVHD. Further, we hypothesize that utilizing a sibling haploidentical donor will result in less GVHD than a parental donor. Secondary aims include evaluating the effect of donor age and donor relationship on overall survival, event-free survival, non-relapse mortality, relapse, graft failure and time to engraftment. The results of this study will help us to develop criteria for optimal haploidentical donor selection. If donor selection is optimized, this could result in improved outcomes following haploidentical transplants. DISCUSSION/SIGNIFICANCE: Haploidentical donors are increasingly used as many patients, especially ethnic minorities, do not have an HLA-matched donor. This will be the largest study of haploidentical HCT in children. The data gathered will allow us to identify important donor characteristics to help guide physician decision-making when choosing a haploidentical donor.

Abstract: Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II–IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II–IV (hazard ratio=3.11, P=0.002) and III–IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II–IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.