Long-term Survival, Organ Function, and Malignancy after Hematopoietic Stem Cell Transplantation for Fanconi Anemia

Abstract

We report on long-term survival in 157 patients with Fanconi anemia (FA) who survived 2 years or longer after their first transplantation with a median follow-up of 9 years. Marrow failure (80%) was the most common indication for transplantation. There were 20 deaths beyond 2 years after transplantation, with 12 of the deaths occurring beyond 5 years after transplantation. Donor chimerism was available for 149 patients: 112 (76%) reported > 95% chimerism, 27 (18%) reported 90% to 95% chimerism, and 8 (5%) reported 20% to 89% donor chimerism. Two patients have < 20% donor chimerism. The 10- and 15-year probabilities of survival were 90% and 79%, respectively. Results of multivariate analysis showed higher mortality risks for transplantations before 2003 (hazard ratio [HR], 7.87; P = .001), chronic graft-versus-host disease (GVHD) (HR, 3.80; P = .004) and squamous cell carcinoma after transplantation (HR, 38.17; P < .0001). The predominant cause of late mortality was squamous cell carcinoma, with an incidence of 8% and 14% at 10 and 15 years after transplantation, respectively, and was more likely to occur in those with chronic GVHD. Other causes of late mortality included chronic GVHD, infection, graft failure, other cancers, and hemorrhage. Although most patients are disease free and functional long term, our data support aggressive surveillance for long periods to identify those at risk for late mortality.

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…In 157 patients with FA who survived ≥2 years after HCT, the incidence of oral cavity cancers, mainly SCC, increased with time (8% and 14% at 10 and 15 years post-HCT, respectively), and SCC accounted for 40% of deaths. 76 In another study of 262 patients with FA, the 117 HCT recipients had a four-fold increased risk of developing SCC. 143 …”

“…About half (N=34) of the studies included patients undergoing HCT for different indications, 15–48 whereas the remainder focused on specific diseases, including myeloid malignancies (N=1), 11 lymphoid malignancies (N=15), 49–63 plasma cell disorders (N=3), 64–66 and benign hematologic disorders such as aplastic anemia and Fanconi anemia (FA) (N=9). 67–76 Only three were prospective. 34,36,51 …”

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

“…Compared to the general population, FA patients have a markedly higher risk of malignancy, particularly squamous cell carcinomas of the aeroesophageal and/or anogenital tracts, in addition to MDS and AML [7, 8, 102–106]. In contrast to the general population, the peak hazard for solid tumors increases in a linear manner after the age of 10 years, increasing by >10%/year after the age of 40.…”

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study

“…11,[13][14][15] Improved outcomes led to the elimination of total body irradiation (TBI) from the preparative regimen for FA HCT using fully matched sibling donors in the past decade. [16][17][18][19] With improved HCT outcomes, more patients with FA have survived to adulthood, [20][21][22] and long-term side effects of HCT, including the increased risk of secondary cancers have become critical considerations for long-term care.…”