Predictors for Autoimmune Cytopenias after Allogeneic Hematopoietic Cell Transplantation in Children

Highlights

• Chemo-naivety before HCT and serotherapy are predictors for developing AIC.

• aGVHD grades II to IV is a predictor for developing AIC.

• IgM, IgG, and IgA levels increase before development of AIC.

• AIC is a rare but severe complication after HCT.

• Recognizing AIC is challenging, and treatment should begin as quickly as possible.

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 of 380 pediatric patients, we evaluated the incidence, outcomes, and related various variables, including immune reconstitution markers to AIC. Three hundred eighty patients (median age, 7.4 years; range, .1 to 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 days (range, 46 to 445) after HCT. Using multivariate analysis we found that chemo-naivety before HCT, acute graft-versus-host disease (aGVHD) grades II to IV, and serotherapy were associated with the development of AIC. Development of AIC was preceded by increased levels of IgM, IgA, and IgG. Immune profiles of total absolute lymphocytes were very similar between AIC patients and control subjects. However, CD3^-CD16⁺CD56⁺ natural killer cells, CD3⁺ T cells, CD3⁺CD4⁺ T cell subset, and CD3⁺CD8⁺ T cell subset were lower in AIC patients. Overall survival was good, at 83% (similar between AIC patients and control subjects). In conclusion, we identified chemo-naivety before HCT, preceding aGVHD grades II to 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.