Characterizing Immune Mediated Cytopenias Following Allogeneic Hematopoietic Cell Transplantation for Pediatric Non-Malignant Disorders

Background Immune mediated cytopenias (IMC) – isolated or combined hemolytic anemia, thrombocytopenia, and neutropenia - are increasingly recognized as potentially serious complications following allogeneic hematopoietic cell transplantation (HCT) for non-malignant disorders (NMD). However, IMC incidence, severity, response to therapy, and risk factors are not well defined. Methods Pediatric patients undergoing HCT for NMD between 2010 and 2017 at a single institution were identified, excluding those experiencing graft failure or death prior to day +100. Demographics and HCT characteristics were obtained from a prospectively-maintained database. A retrospective chart review identified cases of IMC with positive direct Coombs test, anti-platelet antibody, and/or anti-granulocyte antibody; and documented treatment and response. IMC severity was defined by months to resolution: mild (0-3), moderate (3-6), or severe (>6). Results Of 271 NMD HCT recipients, 52 (19%) exhibited IMC at a median of 130 days post-HCT (range, 30-279); 23 (44% of cases) had multiple cell lines affected. IMC disease was mild, moderate, or severe in 44%, 25%, and 31%, respectively, with no deaths attributed to IMC. For those with moderate or severe IMC, all received steroid therapy, with a response rate of 34%. An average of 2.0 unique agents were used to achieve IMC resolution, at a median of 117 days (range 17 – 639). Univariate analysis revealed statistically significant associations between IMC and younger age at HCT (median 3.7 vs. 7.0 years, p Conclusion Immune mediated cytopenias following HCT for NMD in a large pediatric cohort was common at 19%, with limited steroid responsiveness, use of multiple immunosuppressive agents and duration of therapy exceeding 3 months for the majority affected. Patient and transplant characteristics associated with IMC were consistent with previous reports, though we expand these findings with observation of declining donor T-lymphoid chimerism and CD4 counts by day +100, prior to median onset of IMC. While, the pathogenesis of IMC post-HCT for NMD remains elusive, further research may identify approaches to prevent this HCT complication.