Excellent Outcome for Fanconi Anemia Patients Undergoing Hematopoietic Stem Cell Transplantation(HSCT) without Radiation: A Single Center Experience on 103 Patients

Fanconi anemia(FA) is a rare genetic disorder characterized by congenital defects, bone marrow failure and cancer predisposition. Over the past decade, survival after HSCT has greatly improved and the use of protocols without radiation are preferred in order to decrease late complications related to the development of head and neck cancer. In this study we analyzed 103 patients(pts) with FA who were transplanted between 2003 and 2014. The median age at HSCT was 9ys(range: 3-23ys). All pts were transplanted in marrow failure and received bone marrow from matched siblings (MSD) (n=49) or Alternative donors (AD) (n=54). This latter group included 12 other related donors(ORD) and 42 unrelated donors(URD). Preparatory regimen with Cyclophosphamide 60mg/kg(CY60) was given to all pts with MSD or ORD while pts with URD received CY60 + Fludarabine 125mg/m2 + rabbit ATG 5mg/kg. All pts received GVHD prophylaxis with cyclosporine and methotrexate. Three pts died before D+28 and were not evaluable for engraftment (MSD: 2 pts and URD: 1 pt). One patient (MSD) developed primary graft failure, received a 2^nd transplant without success and was finally rescued after a 3^rd transplant with a haploidentical donor. She is alive and well 3ys after HSCT. Ninety-nine pts engrafted but 5 pts developed late graft failure (MSD=2pts; ORD=1pt; URD=1pt) between 50 and 742 days after transplant (M: 84 days). Four out of these 5 pts are alive and well with full donor chimerism after a 2^nd or 3^rd HSCT. At last follow-up, the majority of pts transplanted from AD had full donor chimerism (96%) while approximately 50% of pts with MSD donors had mixed chimerism. Mucositis grade II-III occurred in 70% of pts. Viral infections were more frequent when AD were used(60%) compared to MSD(28%). Hemorrhagic cystitis occurred in 22% of AD transplants and it was uncommon after MSD transplants (only 1 pt). After AD transplantation, acute GVHD grade II-IV occurred in 12/53 evaluable pts and any Chronic-GVHD occurred in 21/38 evaluable pts. MSD had a lower incidence of acute-GVHD (3/47 evaluable pts) while Chronic GVHD occurred in 14/47 evaluable pts. Ninety-one pts are alive between 7 months and 10 years (M: 5 ys) with an overall survival of 87% at 5ys There was no difference in survival according to the type of donor MSD (92%), ORD (92%) and URD(83%). Patients without Acute-GVHD had an overall survival of 98% compared to 58% with acute GVHD (p:0.001). Twelve pts died between 3 and 1855 days after HSCT( M:65 days). Acute or chronic GVHD were the major causes of death (n=8) followed by infections (n=3) and central nervous system bleeding (n=1). Conclusions: HSCT for FA has improved dramatically during the past decade. In this study, the use of non irradiation protocols was associated with an excellent survival, successful engraftment and very low mortality rate.