Rituximab for Children with Immune Thrombocytopenia: A Systematic Review

Abstract

BackgroundRituximab 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 FindingsWe 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 ≥100×109/L) and response (platelet count ≥30×109/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/SignificanceRandomized 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.

Current management of immune thrombocytopenia

“…33 In addition, 2 systematic reviews have evaluated initial response in children with reported pooled response rates of 57% (N ϭ 116) 34 and 68% (N ϭ 323). 35 Projected 1-and 5-year response rates, however, were significantly lower at 33% and 26%, respectively, for children and 38% and 21%, respectively, for adults. Predictors of response to rituximab include shorter duration of ITP, secondary ITP, and previous response to corticosteroids; however, these have not been consistently identified across studies.…”

“…Rituximab has been successful in inducing remission in adults 33,34 and pediatric patients 34,35 with chronic ITP. Two systematic reviews of the adult literature have been published with pooled overall response rates, defined as a platelet count Ͼ 50 ϫ 10 9 /L, of 57% (N ϭ 376) 34 and 63% (N ϭ 313).…”

“…Predictors of response to rituximab include shorter duration of ITP, secondary ITP, and previous response to corticosteroids; however, these have not been consistently identified across studies. [33][34][35] Findings from clinical trials have resulted in several questions regarding the mechanism of action of rituximab. For example, the delay between B-cell depletion and platelet count response in the majority of patients and why a significant proportion of patients fail to respond at all.…”

“…Additional serious adverse events included infection (N ϭ 3), serum sickness (N ϭ 7), hypersensitivity reaction (N ϭ 2), and the development of common variable immunodeficiency in one child. 35 Viral reactivation has also been noted in patients receiving rituximab. Hepatitis B 39 reactivation after rituximab commonly occurs and JC virus leading to progressive multifocal leukoencephalopathy has been reported rarely.…”

Hémorragie intracrânienne compliquant un purpura thrombopénique immunologique aigu de l’enfant : une étude rétrospective nationale

“…Les recommandations d'experts indiquent leur utilisation en cas d'échec de splénectomie ou comme alternative à celle-ci dans les PTI chroniques [20]. Le taux de réponse global (plaquettes supérieures à 50 G/L) est de 62,5 % chez l'adulte [21] et comparable chez l'enfant [22]. Leur utilisation précoce, comme celle des vinca-alcaloïdes [23] peuvent s'avérer utile dans le PTI pour tenter de restaurer au plus vite un chiffre de plaquettes de sécurité si la thrombopénie est réfractaire à la combinaison corticoïdes/immunoglobulines comme dans les observations de Kim et al récemment publiées [24].…”