Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Abstract Development of autoimmune cytopenia (AIC) after allogeneic hematopoietic cell transplantation (HCT) is a serious complication requiring urgent intensification of immunosuppressive therapy. The pathophysiology and predictors of AIC are not completely understood. In this retrospective cohort analysis, including 380 pediatric patients, we evaluated the incidence, outcomes, and related various variables, including immune reconstitution markers to AIC. A total of 380 patients (median age of 7.4 years; range 0.1-22.7) were included of which 30 patients (7.8%) developed AIC in 1 (n=6), 2 (n=6) or 3 (n=16) cell lineages at a median of 133 (46-445) days post HCT. Using multivariate analysis we found that chemo-naivety prior to HCT, acute-graft-versus-host-disease (aGvHD) grade II-IV and serotherapy were associated with the development of AIC. Development of AIC was preceded by an increased level of IgM, IgA, and IgG. Immune profiles of total absolute lymphocytes were very similar between AIC patients and controls. However, CD3-CD16+CD56+ natural killer cells, CD3+ T cells, CD3+CD4+ T cell subset and CD3+CD8+ T subset were lower in AIC patients. Overall survival (OS) was good, 83% (similar between AIC patients and controls). In conclusion, we identified chemo-naivety prior to HCT, preceding aGvHD grade II-IV, and serotherapy as predictors for development of AIC. Increasing levels of IgM, IgA and IgG preceded AIC development. These data provide clues to further study the biology of AIC.