Rituximab for children with immune thrombocytopenia: a systematic review

Abstract

Background: Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP.

Methodology/principal findings: We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9)/L) and response (platelet count ≥ 30 × 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported.

Conclusions/significance: Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.

Figure 1. Flow diagram of study selection process for this systematic review.

This is a modified four-phase PRISMA 2009 flow diagram that maps out the number of records identified, included and excluded, and the reasons for exclusions.

Figure 2. Response rate to rituximab in children with ITP.

This forest plot is created by the software of STATA 11.1. Solid boxes indicate the response rate in each study. Horizontal lines indicated 95% CIs. The diamond indicates the pooled response rate (68%). Test of heterogeneity: I² = 67.5%, P<0.001.

Figure 3. Complete response rate to rituximab in children with ITP.

The diamond indicates the pooled complete response rate (39%). Test of heterogeneity: I² = 56.7%, P = 0.005.

Figure 4. Begg funnel plot with pseudo 95% for studies reporting response.

This plot is created by STATA 11.1. For each study, the response rate is plotted against its standard error. The funnel plot suggests no significant asymmetry, indicating no evidence of substantial publication bias.