Single Center Retrospective Analysis of Outcomes Following Hematopoietic Cell Transplantation (HCT) for Primary Immune Deficiency (PID)

Abstract

Background Successful hematopoietic stem cell transplantation (HCT) is curative in primary immune deficiency (PID), but data on post HCT late effects are scarce. We describe outcomes and late effects in PID HCT survivors at 1 year post HCT. Methods Retrospective data analysis was conducted on consecutive PID HCT recipients from Sept 2007-2017 on IRB approved protocol 0707. Outcomes queried included engraftment, graft versus host disease (GVHD), and late effects in survivors. Data review at 2, 5, and 10 years post HCT including analysis of cognitive outcomes and immune reconstitution are ongoing; specifically impact of disease type, age at HCT, and graft source. Results Thirty-nine PID HCT patients received reduced intensity conditioning (RIC) HCT with 1-year overall survival (OS) of 82%. Median age at HCT was 0.5 years (range 0.08 – 17.4 years) and 72% (28/39) were males. Stem cell source was peripheral blood in 72% (19 unrelated, 9 related), umbilical cord blood in 25.5% (10 unrelated), and bone marrow in 2.5% (1 unrelated). Donors were 16 HLA matched and 23 mismatched. RIC regimen was Busulfan AUC 5000 mcmol/L*min x 2 days, Fludarabine 60 mg/m2\u202f×\u202f6 days, rabbit ATG 2mg/kg x 4 days\u202f±\u202fThiotepa 5mg/kg x 1 day. Incidence of > Grade 2 acute GVHD and limited chronic GVHD was 5% (2/39) and 5% (2/39), respectively. Seven patients died due to infection (4), veno-occlusive disease (1), Grade 4 acute GVHD (1), and intracranial hemorrhage (1). Graft failure (GF) rate was 5% (1 primary GF and 1 secondary GF with EBV infection). Donor chimerism (DC) including T cell, was >95% in 60% and those with mixed chimerism had full T cell DC at 1 year post HCT. In 32 survivors, no cardiac, liver, renal, pulmonary abnormalities, or secondary malignancies were noted. Growth was significantly impacted with median height z-scores of -3, with 69% being Conclusion Successful RIC HCT is curative with excellent 1 year OS of 82% with minimal organ toxicities in PID patients; however, significant growth impairment was observed in the majority with some endocrine abnormalities at 1 year post HCT. While further ongoing analysis is imperative, this emphasizes the need for standardized prospective medical surveillance in order to earlier identify post HCT problems systematically and intervene appropriately to improve outcomes in post HCT PID patients.