Treatment of Resistant Thrombotic Thrombocytopenic Purpura with Rituximab and Cyclophosphamide

Abstract

Thrombotic thrombocytopenic purpura (TTP) is an uncommon acquired disease in adults, especially young women, characterized by fever, neurologic manifestations, microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Treatment with plasmapheresis has increased the survival rate from 10% to greater than 90%. Still, a subset of patients with resistant TTP fail to respond to plasmapheresis or remain dependent on this procedure. We report such a patient who was successfully treated with rituximab and cyclophosphamide. She has now been disease free for more than 6 months. This novel treatment modality for TTP has been described for only a few patients. A well-controlled clinical trial is warranted to determine the role and place of this therapeutic approach in the management of TTP.

How I treat refractory thrombotic thrombocytopenic purpura

“…54,55 More recently, it has been used in patients who are refractory to rituximab, or used in combination with rituximab for TTP patients who are refractory to steroids and PEX. [56][57][58] In a recent case series of 5 patients with refractory TTP (refractory to PEX, steroids, along with vincristine or rituximab or both), who were then treated with 3 to 6 pulses of cyclophosphamide (500-750 mg/m 2 per pulse), a durable platelet recovery was seen at a median period of 10 days after the first cyclophosphamide pulse. 56 Side effects of cyclophosphamide include bone marrow suppression, infection risk, infertility, and a potential long-term risk of myelodysplastic syndrome/leukemia.…”

Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases

“…These reports consisted of small retrospective series or single case reports. [19][20][21][22][23][24][25][26][27][28][29] Moreover, patients usually received concomitant additional immunosuppressive treatments, including vincristine and cyclophosphamide.…”

“…[15][16][17][18] It has been also used as a curative treatment in small retrospective cohorts of patients with acute refractory TTP associated with a severe ADAMTS13 deficiency related to inhibitory anti-ADAMTS13 Abs. [19][20][21][22][23][24][25][26][27][28][29] Twenty-five of 26 patients achieved complete remission, and their follow-up revealed long-term remission in most cases. Rituximab has never been used as a prophylactic treatment in patients with highly recurrent TTP out of an acute episode.…”

Rituximab in the treatment of autoimmune haematological disorders

“…In rare cases where plasma exchange is not possible, rituximab treatment may play an important role in alternative treatment (Martin et al, 2007). In the majority of reports in which safety and tolerability are mentioned, rituximab was well tolerated, with few side effects noted during follow-up (Chemnitz et al, 2002;Zheng et al, 2003;Ahmad et al, 2004;Stein et al, 2004;Yomtovian et al, 2004;Fakhouri et al, 2005;Gianfaldoni et al, 2005;Kosugi et al, 2005;Koulova et al, 2005;Benetatos et al, 2006;Schleinitz et al, 2007). Rituximab infusion reactions were reported in some studies, but were generally mild in nature and did not warrant the discontinuation of rituximab (Sallah et al, 2004;Heidel et al, 2007;Scully et al, 2007).…”