Biological stratification of clinical disease courses in childhood immune thrombocytopenia

Background In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. Objective To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. Methods Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. Results In the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc‐receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti‐platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80‐1.00) and specificity was 0.67 (95% confidence interval, 0.53‐0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow‐up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. Conclusions The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.