Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia

Abstract

AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA)–associated bone marrow failure (BMF)/aplastic anemia (AA) and hematological malignancy. We performed a retrospective multicenter study on 813 children with FA undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years (interquartile range [IQR], 3.4-4.0). Median age at transplant was 8.8 years (IQR, 6.5-18.1). Overall survival (OS); event-free survival (EFS); and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) at 5 years were 83% (80%-86%), 78% (75%-81%), and 70% (67%-74%) respectively. OS was comparable between matched family donor (MFD; n = 441, 88%) and matched unrelated donor (MUD; n = 162, 86%) and was superior to that of mismatched family donor (MMFD) or mismatched unrelated donor (MMUD; n = 144, 72%) and haploidentical donor (HID; n = 66, 70%; P < .001). In multivariable analysis, a transplant indication of acute myeloid leukemia/myelodysplastic syndrome compared with AA/BMF, use of MMFD/MMUD and HID compared with MFD, and fludarabine-cyclophosphamide (FluCy) plus other conditioning compared with FluCy independently predicted inferior OS, whereas alemtuzumab compared with antithymocyte globulin was associated with better OS. Age of ≥10 years was associated with worse EFS and GRFS. Cumulative incidences (CINs) of primary and secondary graft failure were 2% (1%-3%) and 3% (2%-4%) respectively. CINs of grade 2 to 4 acute GVHD, grade 3 to 4 acute GVHD, and chronic GVHD were 23% (20%-26%), 12% (10%-15%), and 8% (6%-10%), respectively. The 5-year CIN of secondary malignancy was 2% (1%-3%). These data suggest that HSCT should be offered to patients with FA with AA/BMF at a younger age in the presence of a well-matched donor.