Further Personalizing Medicine in Immune Disorders: Genomic Findings and Hematopoietic Cell Transplantation Survival

Hematopoietic cell transplantation (HCT) provides effective long-term management for some inborn errors of immunity. Genetic findings can inform donor selection, considerations in conditioning intensity and agents, and graft-versus-host disease prophylaxis. Exome/genome sequencing is increasingly accessible but of uncertain clinical utility. We aimed to evaluate the clinical utility of comprehensive genomic evaluations through review of HCT at our center.

We performed exome/genome sequencing on pre-HCT samples from participants between 2017 and 2023. We reported primary findings (PF) and secondary findings (SF). Post hoc, we analyzed medication and pharmacogenetic (PGx) data.

We analyzed pre-HCT exome/genome sequencing (n = 84 exome, n = 63 genome, n = 32 with both) for 179 probands. Most (143/179; 79.9%) had a PF underlying the HCT indication, with GATA2 being most common (n = 59). Three percent of participants had an SF predisposing to cancer or cardiovascular disease. Most (n = 108/179; 60.3%) received ≥1 medication(s) that may have been further optimized with PGx. Using Kaplan-Meier survival analysis, we compared the survival rates of participants with 0, 1, and ≥2 genomic risk factors (GRF: absence of PF; presence of SF or PGx). Survival at 3 y was 94.8%, 84.8%, and 58.5% for those with 0, 1, and ≥2 GRF, respectively (log-rank: 16.10, df = 2, P  = 0.0003), indicating statistically significant survival differences by GRF.

Comprehensive genomic evaluation is an emerging avenue for tailoring HCT approaches, and identification of HCT-relevant findings may be common. On multivariate analysis, GRF was associated with survival in this retrospective cohort. Prospective research is warranted to further integrate genomic data into precision treatment.