Hematopoietic Stem Cell Transplantation is the only curative approach for the hematological complications of Fanconi Anemia. However, patients with FA remain at increased risk for HSCT-specific late effects and FA-associated complications including solid tumors, which may affect their long-term outcome.

We performed a single-institutional, retrospective review of late effects and long-term outcome in patients with FA who underwent HCST from alternative donors at MSKCC from March 1999 to December 2012. This review was approved by MSKCC IRB/Privacy Board. Twenty-two patients including 14 males and 8 females who underwent T-cell depleted HSCT and survived more than one-year post-transplant were eligible for inclusion in this study. The hematologic diagnoses of these patients were: severe aplastic anemia (SAA, n=11), myelodysplastic syndrome (MDS n=6) and acute myelogenous leukemia (AML n=5). Cytoreduction regimens included Total Body Irradiation (TBI), Cyclophosphamide (CY) and Fludarabine (FLU) (n=18) or Busulfan, CY and FLU (n=4). Donors were unrelated matched (n=9), unrelated mismatched (n=5) or related mismatched (n=8).

The median post transplant follow-up for the 22 patients was 6.7 years (range 1.1- 15.1 years). Of the 22 patients who survived more than 1 year post HSCT, 20 are alive and 19 are alive disease-free, with overall survival and disease-free survival rates of 90.9% and 86.3% respectively for this patient group. Two female patients died of complications related to squamous cell carcinoma of the tongue and the vulvo-vaginal area respectively; one patient developed a relapse of MDS and is alive following a second transplant. Full donor chimerism was present in 18 of 20 evaluable patients. No chronic GVHD was observed in any of the 22 patients who received grafts from alternative donors. Of the 18 patients who received a TBI based regimen, 4 patients (22%) developed hypothyroidism post transplant, 7 patients (39%) developed insulin resistance (HOMA-IR >2.6) and one patient developed Insulin dependent diabetes mellitus, a year after transplant. Germ cell dysfunction was noted in 8 of 11 evaluable males and 4 of 5 evaluable females following a TBI based regimen. Among 4 patients receiving a Busulfan-based regimen, only one patient developed hypothyroidism. Prior to transplant, 13 patients (59%) had elevated ferritin levels (>500ng/ml) and seven of these 13 patients had received >20 transfusions. Post transplant, 12 patients had persisting high ferritin levels and six underwent phlebotomy. None of the patients had documented adverse cardiac or pulmonary late outcomes post-transplant.

In summary, patients with FA are at risk for treatment-related late effects, and multidisciplinary follow up of patients with FA (including cancer screening) is essential for the early detection and management of late complications. Patients with FA who survive greater than one year post transplant have a very good outcome. However, these patients remain at risk for solid tumors of the head and neck and anogenital area post transplant. It is hoped that newer regimens that minimize radiation exposure and the use of T-cell depletion associated with minimal GvHD will further decrease the risks of solid tumors and other adverse late effects in patients with FA post transplant.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.