LAUSR

Introduction Outcomes of hematopoietic stem cell transplant (HSCT) in Fanconi Anemia (FA) have markedly improved with use of low dose cyclophosphamide and fludarabine and the advent of T-cell depleted donor grafts. Most recently, use of busulfan with radiation-free conditioning has demonstrated excellent results. While long-term survival has improved, little is known regarding late effects in individuals with FA transplanted using a busulfan containing regimen. Methods We retrospectively collected clinical data on 47 subjects with FA who underwent HSCT at our center between June 2009 and June 2017 using a busulfan, cyclophosphamide, fludarabine and rabbit anti-thymocyte globulin regimen with T-cell depleted graft (Figure 1). Forty-five subjects who survived ≥1 year post-HSCT were included in the analysis. Results Our cohort has 25 females and 20 males with median age at HSCT of 7 years (range, 4-18). Indication for transplant was severe aplastic anemia in 80% (n=36), and myelodysplastic syndrome in 20% (n=9). Median follow-up was 4 years (range, 1- 8). One subject died 2.5 years after transplant of liver disease, the remainder are surviving. There was no late graft failure. One subject developed EBV-associated PTLD 2.5 months post-HSCT, successfully managed with anti-viral T-cells. There were no other secondary malignancies. Two subjects were diagnosed with chronic GVHD (GI, lung), one at 2 years and one at 7 months post-HSCT, respectively, with 93% of patients (n=42) free of GVHD. Endocrine abnormalities were frequent, with 52% of subjects diagnosed as hypothyroid. One subject developed insulin dependence during transplant and continues on this therapy 8 years later. Bone density was normal in 87% (n=33/38) with median adjusted Z score of 0.55. Gonadal function was normal in 60% of females, with 33% and 7% with POI and partial hypogonadism respectively (n=15, median age 11.6 years). Gonadal function was normal in 86% of males with 7% and 7% with hypergonadotropism and precocious puberty respectively (n=14, median age 12 years). Hypertension was seen in 9% (n=4/44). Pulmonary complications included 2 patients with a restrictive defect noted on pulmonary function testing (PFT). Cardiac function was normal in 96% with 2 individuals demonstrating mild left ventricular dysfunction, one of whom has increased cardiac iron. Depression, anxiety and chronic headaches were noted in 3, 3, and 2 subjects respectively. Conclusions Our cohort received a busulfan-based preparative regimen, evaluated at 1 to 8 years post-transplant, and demonstrates low rates of graft rejection, post-transplant malignancy and GVHD. While endocrine abnormalities remain common, pulmonary and cardiac complications were rare. Ongoing longitudinal analysis beyond the 10 year mark will be important to further characterize this cohort and the success of recent alterations to their preparative regimen.