Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone

Abstract

Objectives: To assess initial and long-term outcome of children with persistent/chronic idiopathic thrombocytopenic purpura (ITP) treated with 4 infusions of rituximab and three 4-day cycles of dexamethasone (4R+3Dex) including cohorts with most benefit and/or treatment associated toxicity.

Study design: All pediatric patients with ITP at Weill-Cornell who received 4R+3Dex were included in this retrospective study. Duration was median time from first rituximab infusion to treatment failure. Patient cohort included 33 children ages 1-18 years with persistent/chronic ITP; 19 were female, 10 of whom were adolescents. Every patient had failed more than 1 and usually several ITP treatments.

Results: Children were treated with rituximab, 375 mg/m² weekly for 4 weeks and three 4-day courses of dexamethasone 28 mg/m² (40 mg max). Average age of nonresponders was 7.75 years, and initial responders averaged 12.7 years (P = .0073); 30% maintained continuing response at 60 months or last check-up. Eight of the 10 patients who underwent remission were female with ITP <24 months prior to initiating 4R+3Dex. All responding male patients except 2 relapsed.

Conclusions: Durable unmaintained ITP remission after 4R+3Dex was seen almost exclusively in female adolescents with <24 months duration of ITP. This provides a new therapeutic paradigm for a subpopulation with hard-to-treat chronic ITP. The pathophysiology of ITP underlying this distinction requires further elucidation.

Keywords: autoimmune disease; immune therapy; platelets; thrombocytopenia.

Figure 1

Kaplan-Meier plot of male and female patients with ITP treated with 4R+3Dex. Male and female patients had similar initial response rates, but over time all but 2 male patients relapsed, whereas 80% of female responders maintained a durable remission without additional treatment.

Figure 2

Kaplan-Meier curve of response rates in pediatric patients with ITP based on duration of diagnosis. Duration of ITP prior to initiation of 4R+3Dex did not predict initial response to therapy but did have a significant effect on the likelihood of maintaining remission.

Figure 3

The effects of sex and duration of ITP on prognosis after 4R+3Dex therapy. In this graph, we stratify many of the study variables together. Female patients who were diagnosed less than 24 months before receiving 4R+3Dex therapy were most likely to achieve and maintain a response.