Combination immune-based therapy for chronic ITP

Abstract

Idiopathic thrombocytopenia purpura (ITP) is a common pediatric disorder that often dramatically presents with sudden onset bruising, petechiae, and (typically quite severe) thrombocytopenia. While various therapies (glucocorticoids, intravenous gamma globulin, intravenous anti-D) can transiently increase the platelet count, serious bleeding from acute ITP is uncommon, with little evidence that preemptive treatment reduces either the risk of serious bleeding or the already low (10-15%) incidence of developing chronic ITP. Given the side effects commonly associated with these drugs, the pendulum has to some degree swung back toward observation without pharmacologic intervention for newly diagnosed patients. Chronic ITP is different. Over time bleeding manifestations can become more severe, lifestyle limitations become more burdensome, and bleeding from accidental trauma remains a constant concern. While splenectomy has long been used to treat chronic ITP, there remains a life-long increased risk of infection despite use of pre-splenectomy immunizations and prophylactic antibiotics. Various immunomodulatory therapies have also been used, joined more recently by thrombopoietin mimetic drugs. Unfortunately, many children with chronic ITP respond to these treatments either transiently, or not at all. In this volume of The Journal, Oved et al report a retrospective review of 33 children treated with a combination of 4 weekly doses of rituximab plus three 4-day pulses of dexamethasone. Each drug has been used individually for chronic childhood ITP, and prior studies in adults suggest that combination therapy may be more effective than either drug alone. All patients had received at least 1—and often many—prior treatments for chronic ITP. Approximately half of the patients who received combination therapy initially responded, and one-third maintained prolonged remissions 10-58 months after treatment; more interesting, almost all of the long-term responders were females who were treated <24 months from their initial diagnosis of ITP. Other than the expected GI upset from steroids and transient hypogammaglobulinemia from rituximab, treatment was generally well tolerated. These results suggest that this combination would be a reasonable early intervention for a female with chronic ITP, whereas alternative interventions should be pursued for male patients or those with prolonged duration of thrombocytopenia. Article page 225 ▶ Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of DexamethasoneThe Journal of PediatricsVol. 191PreviewTo 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. Full-Text PDF