Successful Hematopoietic Cell Transplantation in Patients with Fanconi Anemia with Severe Renal Insufficiency

Introduction Hematopoietic cell transplantation (HCT), the only proven cure for the hematological manifestations of Fanconi Anemia (FA) is particularly challenging in patients with renal insufficiency. Objective To analyze outcome of HCT in FA patients with pre-existent renal insufficiency Methods This retrospective single center cohort study reports outcomes of 20 FA patients with pre-existent renal insufficiency, defined as glomerular filtration rate (GFR) ≤70ml/min/1.73m2 by nuclear medicine scan, who underwent HCT from 1997-2021. Results Median age was 5 years (range, 0.75-24) and median GFR 51.2 ml/min/1.73m2 (range 8-68.4). Median duration of follow up is 14.3 (range <1 month-14.3) months. Two patients received dialysis prior to HCT. HCT indications were severe marrow failure (n=16), MDS/AML (n=2), T ALL (n=1), and high risk biallelic BRCA2 genotype (n=1). Other genotypes included FANCA, B, C, D2 and unknown in 2 patients. Conditioning regimens varied by donor source and disease at time of HCT but included cyclophosphamide (CY) and mesna per institutional guidelines in all patients (Table 1) and fludarabine (FLU) in 19 patients. Four patients had no dose reduction in CY or FLU. Based on pre HCT GFR, the dose of CY was reduced by 50% in 5 patients and the dose of FLU reduced by 20% (n=6), 50% (n=4) or 75% (n=1), with 5 patients having both CY and FLU adjusted. GVHD prophylaxis included cyclosporine, T cell depletion and either methylprednisolone or mycophenolate. All but one evaluable patients achieved neutrophil engraftment at a median of 10 days (range 5 -24) after HCT. Only one patient developed grade II-IV acute GVHD, and no patient developed chronic GVHD. Six patients required dialysis during the HCT course, 2 of whom had chemotherapy dose reductions. 5 of these 6 patients died within the first 2 years after HCT. Of the 9 patients who did not have dialysis before transplant and who also received dose reduction of chemotherapy, the probability of survival at 1 year is 65%% (25-87%). Two of 20 patients underwent kidney transplant at 7 and 8 years after HCT. Conclusion In summary, FA patients with concurrent moderately severe renal insufficiency can safely and effectively undergo HCT with chemotherapy dose adjustments. However, requiring dialysis before HCT is associated with very poor outcomes and HCT should be avoided if possible.