Outcomes of Related and Unrelated Donor Searches Among Patients with Primary Immunodeficiency Diseases (PIDs) Referred for Allogeneic Hematopoietic Cell Transplantation (HCT).

Patients with PIDs are potentially cured by allogeneic HCT, although related donor searches for PID patients have the additional selection factor of the inherited disease and therefore may yield more limited options than searches for hematologic malignancy patients. Unrelated donor options are thus critical in these patients. We evaluated the outcomes of donor searches among PID patients referred to the National Institutes of Health (NIH) for HCT, where donor options included matched related donors (MRD), HLA-haploidentical (haplo), or 7-8/8 HLA-matched unrelated donors (mMUD/MUD). After IRB approval (NCT03188419, clinicaltrials.gov), retrospective chart review of PID patients referred to NIH for HCT between 3/30/12-2/27/18 was performed. Patient and donor demographics, MUD search results, HLA typing, pedigrees, mutation testing, and donor selection data were collected. For the purposes of this study, patients with unknown PID mutation were considered to have no related donor options. The HapLogic 8/8 HLA-match algorithm was used to predict the likelihood of a successful MUD search and categorized as very good, good, fair, poor, very poor, or futile per the MSKCC Search Prognosis method. Patient (n = 161), donor, and HCT (n = 109) characteristics are shown in Fig 1, with significant differences by PID mode of inheritance in patient age, disposition (receipt of HCT or not), donor source, and donor relatedness. Of living 1st degree relatives (median 3 (range 0-12) per patient), a median of 1 donor remained for autosomal dominant and X-linked (XL) diseases after HLA typing, mutation testing, and other exclusions, and a median of 2 donors remained for autosomal recessive (AR) diseases. Among patients with a PID of known mode of inheritance (n = 142), the best related donor was haplo for 100 (70%) patients, with 56 (39%) haplos age 40+ years and 4 (3%) 2nd degree haplos; 13 (9%) had no family donor options. The best related donor was a heterozygote/asymptomatic carrier of the PID mutation in 36 (49%) patients with AR or XL disease (n = 73). Among patients with MUD search performed (n = 139), 53 (38%) had very poor/futile 8/8 MUD searches, including 6 (31%) of those with unknown PID mutation and therefore no family donor options. The predicted likelihood of a successful MUD search was lower for those of non-European ancestry, p = 0.01. The majority of patients of Hispanic or African ancestry had very poor/futile MUD searches, 71% and 63%, respectively. No HCT recipients with very poor/futile MUD searches (n = 38) received 8/8 MUD grafts. Median time from HLA typing to HCT was 7 months. Haplo and MUD options are critical to enable HCT for patients with PID. Related donor options are reduced and haplos age 40 years+ and/or mutation carriers are often the best family option. MUD search success remains low for those of non-European ancestry and this is of particular concern for patients with PID due to an unknown genetic defect. [ABSTRACT FROM AUTHOR]