Background: HCT is the treatment of choice for many children with non-malignant diseases. The aim of this study is to determine major transplant outcomes among pediatric patients (pts) transplanted in Brazil. Patients and methods: This retrospective study included 300 pts with Bone Marrow Failures syndromes (65%, n = 193), Primary Immunodeficiencies (24%, n = 72), Inborn Errors of Metabolism (7%, n = 22) and Hemoglobinopathies (4%, n = 13) who received first allo-HCT between 2010 and 2014 at 11 Brazilian BMT centers. All pts received unmanipulated bone marrow (BM, 86%) or cord blood (CB, 14%) grafts. HCT donors included match related (MRD, n = 140, 47%), fully matched unrelated (MUD, n = 108, 36%) and mismatched unrelated (MM-URD, n = 52, 17%). Reduced intensity conditioning was given to 167 pts (56%). Most (78%) received GVHD prophylaxis with calcineurin inhibitor plus methotrexate. Grading of aGVHD and cGVHD were per Glucksberg and NIH criteria and were uniform among all centers. Results: Median age was 8 y/o (range, .6 to 17) and 62% (n = 185) were male. With median follow up of 4.5 years, 4yoverall survival (OS) was better for MRD compared to matched URD or mismatched URD transplants (84% versus 71% versus 69%, respectively; P = .01). When compared MM-URD BM (n = 26), matched (n = 11) or mismatched unrelated CB (n = 26) transplant pts had a lower OS (HR = 2.73; P = .04). Twentytwo pts died before D+21 and therefore were not evaluable for engraftment. Primary graft failure (GF) was observed in 21 pts and was significantly higher after mismatched CB transplants (OR = 7.43; P = .03) compared to MM-URD BM transplants. 257 pts engrafted and 22 developed secondary GF at a median of 193 days (range, 39-431). Acute GVHD grade II-IV occurred in 47 pts at a median of 28 days after HCT with a cumulative incidence (CumInc) at 3 months of 16% (95% CI, 11-20). Chronic GVHD was reported in 60 pts at a median of 189 days after HCT with a CumInc at 2 years of 20% (95% CI, 15-24). Acute and chronic GVHD CumInc were not significantly different across all donor types. Seventy-three pts died at a median of 69 days after HCT. Major causes of death included infection (51%) and GVHD (15%). One-year and 100days TRM were 20% (95% CI, 15-24) and 17% (95% CI, 13-22), respectively. Conclusions: Children and adolescents with non-malignant diseases can achieve excellent outcomes after HCT from MRD in Brazil. We observed a high early mortality after HCT from unrelated CB donors in our study. For children lacking MRD, an URD donor is a suitable option, particularly from a MUD. Confirming earlier reports, incidence of chronic GVHD was low in this setting. This is the first pediatric multicenter study in Brazil for nonmalignant diseases and future studies will focus on strategies to reduce early mortality after unrelated CB HCT and will explore the role of HCT from haploidentical donors for children lacking MRD or MUD.
