Characterizing Immune-Mediated Cytopenias After Allogeneic Hematopoietic Cell Transplantation for Pediatric Nonmalignant Disorders

Immune-mediated cytopenias (IMC)-isolated or combined hemolytic anemia, thrombocytopenia, or neutropenia-are increasingly recognized as serious complications after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant disorders (NMD). However, IMC incidence, duration, response to therapy, and risk factors are not well defined. This retrospective chart review identified cases of IMC with serologic confirmation among patients who underwent HCT for NMD at a single institution between 2010 and 2017. IMC after HCT for NMD in a large pediatric cohort (n = 271) was common with a cumulative incidence of 18%, identified at a median of 136 days after HCT. Treatment included prolonged immune suppression (>3 months) in 58% of all IMC cases, 91% when multiple cell lines were affected. Multiple therapeutic agents were used for the majority affected, and median time to resolution of IMC was 118 days from diagnosis. Fine-Gray competing risk multivariate regression analysis identified a combined risk factor of younger age (<3 years) and inherited metabolic disorder, as well as hemoglobinopathy (at any age) associated with 1-year incidence of IMC (P < .01). We expand these findings with the observation of declining donor T-lymphoid chimerism from day 60 to 100 and lower absolute CD4+ counts at day 100 (P < .01), before median onset of IMC, for patients with IMC compared to those without. In this cohort, 4 deaths (8%) were associated with IMC, including 2 requiring second transplantation for secondary graft failure. Although the pathogenesis of IMC post-HCT for NMD remains elusive, further research may identify approaches to prevent and better treat this HCT complication.