A Clinical Prediction Score for Course of Disease in Newly Diagnosed Childhood Immune Thrombocytopenia

Background Newly diagnosed childhood immune thrombocytopenia (ITP), an acquired autoimmune bleeding disease, has a good prognosis: 60-70% of patients recover spontaneously 3 months after diagnosis (transient ITP), whereas 10-20% remain thrombocytopenic beyond 12 months (chronic ITP). A key clinical challenge is the early identification of a patient's disease course to counsel families, inform treatment decisions, and guide additional diagnostics, e.g. screening for systemic autoimmune diseases, immunodeficiencies or genetic thrombocytopenia. Several clinical predictors have been proposed (Heitink-Pollé et al. Blood 2014;142(22)), but it is unclear how they can be integrated to predict disease outcomes. Objective To develop and validate a clinical prediction model for transient vs. prolonged disease courses in children with newly diagnosed ITP, using clinical characteristics at diagnosis. Study design Model development and validation in a multinational prospective observational cohort; external validation in a multicenter randomized controlled trial. Methods Using modern statistical methods, we extended a score by Edslev et al. (BJH 2007; 138) into an updated, multivariate prediction score, using individual patient data from newly diagnosed childhood ITP patients included in the observational, prospective Nordic Pediatric Hematology-Oncology ITP study (NOPHO; N=377; data shared by original investigators). Transient ITP was defined as complete recovery by platelet count 3 months after diagnosis (NOPHO, ≥150x109/L; TIKI, ≥100x109/L). The model was developed by penalized regression (Ridge) with ten-fold cross-validation in patients included during the first half of the NOPHO study period (derivation cohort, N=233) and subsequently validated in the second half (validation cohort, N=144). External validation was performed on children with newly diagnosed ITP included in the Dutch randomized controlled trial Treatment With or Without IVIg for Kids With ITP (TIKI; N=200; N=100 randomized to IVIg and N=100 carefully observed; Heitink-Pollé et al.Blood 2018; 132(9)). Inclusion criteria of both studies included a diagnosis platelet count ≤20x109/L and age below 16 years. Results Case-mix analyses showed that TIKI and NOPHO cohorts had comparable baseline characteristics, considering age, gender, preceding infections and bleeding. The rate of transient ITP was 67% (NOPHO) and 73% (TIKI). Seven predictors were included in the model: age (years; penalized odds ratio [OR