Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Fanconi Anemia: Results of a Single Center with a Fludarabine-Based Conditioning Regimen

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the only curative treatment for bone marrow failure (BMF) and hematologic complications of Fanconi anemia (FA). The evolution remains affected by the toxicity, the risk of graft failure, and clonal evolution. This study aimed to identify factors affecting outcomes in FA patients after allo-HSCT. We included FA patients who underwent allo-HSCT between January 2006 and December 2021. The conditioning regimen was cyclophosphamide/fludarabine (Cy/Flu) ± rabbit anti-thymocyte globulin (ATG). Bone marrow was the stem cell source from HLA-matched related donors in all transplants. Twenty-three patients, 19 with BMF and 4 with MDS/clonal evolution, were included. The median age was 11 years (5–39 years). Five patients (22%) received serotherapy with the conditioning regimen. Engraftment occurred in all patients without severe regimen-related toxicity. The 100-day cumulative incidence (CI) of grade II-IV acute GvHD (a GVHD) and 5-year CI of chronic GvHD (cGVHD) were 17% and 32%, respectively. The 5-year CI of late secondary graft failure was 10.5%. Two patients developed clonal evolution (AML; n = 2) and one patient developed nephrotic syndrome (n = 1). The 10-year overall survival (OS) and event-free survival (EFS) were 80% and 75%, respectively. There was a trend toward a better EFS in patients aged <10 years compared to patients aged ≥10 years (100% versus 61%; p = 0.06). At the last follow-up, 18 patients were alive, and 4 expired. Causes of death were infections with refractory GVHD (n = 1), graft failure (n = 2), and renal failure (n = 1). Despite the small patient population, we show excellent outcomes, particularly for those transplanted in the first decade.