Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia

Abstract

Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). We performed retrospective predictor analyses for HCT outcomes in FA for pediatric and young adult patients transplanted between 2007 and 2020 across three large referral institutions. Eighty-nine patients, 70 with bone marrow failure +/- cytogenetic abnormalities, 19 with MDS/AML, were included. Five-year overall survival (OS) was 83.2% and event-free survival (EFS) was 74%. Age ≥19, HLA mismatch and year of HCT were multivariable predictors (MVPs) for OS, EFS and treatment-related mortality (TRM). In the pediatric group, TCD was a borderline MVP (P = 0.059) with 5-year OS of 73.0% in TCD vs. 100% for T-replete HCT. The cumulative incidence of day 100 grade II-IV aGvHD and 5-year cGvHD were 5.6% and 4.6%, respectively. Relapse in the MDS/AML subgroup occurred in 4 patients (16%). Graft failure was seen in 9 patients (TCD 6/37 [16%]; T-replete 3/52 [5.7%]). Six patients developed malignancy after HCT. Survival chances after HCT for FA are excellent and associated with high engrafted survival and low toxicity. Age ≥19, HLA mismatch, year of transplant and 'TCD in the <19 years group' (although borderline) were found to be negative predictors for survival.

Fig. 1. Outcomes for full cohort.

Overall survival (a) and event-free survival (b) in our full cohort and overall survival (c) and event-free survival (d) in patients younger than 19 years of age at time of transplant.

Fig. 2. Outcomes by age.

Event-free survival (a) and treatment related mortality (death by other cause than relapse; b) by age <19 years compared to age ≥19 years.

Fig. 3. Outcomes in patients <19 years old by T-cell depletion.

Overall survival (a) and event-free survival (b) in patients younger than 19 years, by T-replete transplants versus ex vivo T-cell depleted transplants.