Long-Term Follow-up after Hematopoietic Stem Cell Transplantation for Patients with Fanconi Anemia: A Single Center Experience on 157 Patients Surviving 2 or More Years after Transplant

Allogeneic transplantation is the only curative treatment for the hematological complications of Fanconi anemia. Survival after transplantation has improved dramatically over the past decade, however, only limited data are available regarding late complications after transplantation.  Therefore, we studied late complications in 157 patients who survived for at least 2 years after their first transplantation, between 1988 and 2011.  The median follow up of this cohort is 9 years (range 2 – 25).  Marrow failure was the most common Indication for transplantation (80%) and most (71%) grafts from a related donor. Bone marrow was the predominant graft (89%).  Chimerism studies were available for 147 of 157 (94%) patients; at last follow up, 110 of 147 (76%) patients reported donor chimerism >95%, 27 (18%), between 90-95%, 8 (5%), <90% and the remaining 2 patients (1%), <30%.  The 2-year cumulative incidence of chronic GVHD at 2-years was 35%. At study entry 32 of 55 patients with chronic GVHD were receiving immunosuppressive treatment.  The probabilities of overall survival for patients who survived at least 2 years was 95%, 90% and 79%, 5-, 10- and 15-years after transplantation.  Late mortality was associated with transplant period (prior to 2003), history of chronic GVHD and, occurrence of squamous cell carcinoma (SCC).  The 10-year probability of overall survival in those with and without chronic GVHD was 97% and 76%, respectively (p=0.002).   The cumulative incidence of squamous cell carcinoma (SCC) at 10ys was 8% and at 15ys was 14%.  SCC was more common in those who reported chronic GVHD compared to those without chronic GVHD (14% vs. 4%, p=0.03).  Endocrine dysfunction was common with hypogonadism in 40% of patients and hypothyroidism in 25%.  Normal pregnancies occurred in 4 females with normal offspring.  Neurological, auditory, visual, pulmonary, hepatic and renal complications were disease-related or transplant procedure but occurred at substantially lower frequencies.  There were 20 deaths (13%) that occurred after 2 years. SCC was the predominant cause of death (n=8). Other causes of death include, chronic GVHD (n=6), rejection (n=2), pulmonary complications (n=2), urinary sepsis (n=1) and hepatitis C (n=1).  In summary, most long-term survivors are disease-free and lead functional lives.  However, for those patients with late complications of transplantation or its effects, efforts must be directed at lowering morbidity and mortality.