Identification Of Factors That Can Predict a Response To Intravenous Immunoglobulin Treatment In Children With Immune Thrombocytopenic Purpura

Immune thrombocytopenic purpura (ITP) is a common benign bleeding disorder characterized by isolated thrombocytopenia caused by the immune-mediated destruction of platelets. The 2004 Japanese Guidelines for Childhood ITP recommended intravenous immunoglobulin (IVIG) as first-line therapy for children with ITP, because this strategy results in more rapid increases in platelet counts when compared with oral steroid therapy. However, predictive markers of the response to IVIG have not been well defined. The present study therefore evaluated whether clinical and laboratory findings before treatment could predict the response to IVIG and progression to chronic ITP.

We reviewed the clinical data of 49 newly diagnosed patients (< 18 years) with ITP who were given IVIG as initial treatment at Japanese Red Cross Nagoya First Hospital from 1997 to 2011, and evaluated the short-term response to IVIG as outcomes at 2 weeks after IVIG and the long-term response to IVIG as thrombocytopenia-free survival (TFS). TFS was defined as the probability of survival without treatment failure (death, relapse, disease progression requiring other therapeutic intervention, or progression to chronic ITP) after initial IVIG and was estimated by the Kaplan-Meier method.

Short-term response to IVIG was observed in 40 patients (82%), and long-term treatment response, defined as 1-year TFS, was 65%. At 6 months after initial IVIG treatment, seven patients (14%) progressed to chronic ITP. In multivariate analysis, lower white blood cell (WBC) count at diagnosis was identified as the only independent risk factor for the short- or long-term response to IVIG (P=0.007 or P=0.043, respectively) and the progression to chronic ITP (P=0.034). Patients with WBC count<7.0×10⁹/L had a lower probability of TFS (41% vs. 77%, P=0.003) and a higher rate of progression to chronic ITP (29% vs. 6%, P=0.040) than those with WBC count ≥7.0×10⁹/L. None of the other variables, including gender, age at diagnosis, season of onset, initial platelet count, initial hemoglobin level, preceding infection, fever at diagnosis, H. pylori infection, total and daily dose of IVIG, product of IVIG, and laboratory findings including CRP, TP, T-bil, LDH, AST, ALT or BUN, were significantly associated with the response to IVIG and the progression to chronic ITP in multivariate analysis.

In conclusion, this study showed that WBC count at onset of ITP is a strong predictor of short- and long-term treatment response to IVIG and the development of chronic ITP in pediatric patients with ITP. For patients with low WBC count, the addition of other agents, such as steroids, to IVIG at the time of initial diagnosis might improve the treatment outcomes.