The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study.

Thrombopoietin-receptor agonists (Tpo-RAs) are highly effective in immune thrombocytopenia (ITP). Recently, cases of durable remission after Tpo-RA discontinuation in adult ITP have been reported. We aimed to describe the subset of patients in whom transient Tpo-RA therapy may induce a durable response. We studied all adults with primary ITP treated with at least one Tpo-RA over a 5-year period (n = 54) and seen at one of three participating referral centres in France. Tpo-RAs were discontinued in 20 of 28 patients who achieved a complete response. We excluded six patients because a previous treatment at the start of Tpo-RA treatment may have interfered with the response. Overall, eight patients with chronic ITP showed a sustained response [median follow-up: 13·5 months (range 5-27 months)]. We could not identify a predictive factor of sustained response. In conclusion, a substantial proportion of ITP patients receiving Tpo-RAs can maintain a durable response after treatment discontinuation.

Profound symptomatic hypogammaglobulinemia: a rare late complication after rituximab treatment for immune thrombocytopenia. Report of 3 cases and systematic review of the literature.

INTRODUCTION: B-cell depletion with rituximab (RTX) is widely used to treat autoimmune diseases, especially as second-line therapy for immune thrombocytopenia (ITP). The incidence of RTX-induced hypogammaglobulinemia is unknown because of heterogeneous follow-up and confounding factors such as concomitant immunosuppressive treatments in most patients. We describe 3 cases and attempted to determine the incidence of RTX-induced hypogammaglobulinemia by a systematic review of the literature. METHODS: We retrospectively analyzed 189 ITP patients receiving RTX in 3 referral centers in France and conducted a systematic review of 32 studies (results published 2001-2014) reporting the use of RTX for ITP, particularly searching for symptomatic secondary hypogammaglobulinemia. We also searched for case reports of hypogammaglobulinemia after RTX initiation for ITP. RESULTS: Of the 189 patients, 3 showed symptomatic hypogammaglobulinemia more than 2years after RTX infusion (initial immunoglobulin level was normal). All 3 presented recurrent severe infections. In 2, the outcome suggested common variable immunodeficiency. In patient 3, the peripheral blood lacked CD19(+)CD20(+) B cells and the bone-marrow B-cell precursor level was impaired. Among 1245 ITP patients in the literature who received RTX for ITP, gammaglobulin level was monitored before and after RTX initiation for 351 (28%). For 192 (55%), dosages were available and we identified 21 patients with secondary hypogammaglobulinemia, usually not symptomatic, 14 of whom had received concomitant dexamethasone. Finally, we found 4 case reports of ITP and symptomatic hypogammaglobulinemia possibly related to RTX according to the authors. CONCLUSIONS: This large analysis led us to recommend monitoring serum immunoglobulin level before and repeatedly after RTX initiation for ITP. Physicians should be aware of hypogammaglobulinemia as a rare but severe complication of RTX.