Long-term follow-up of idiopathic thrombotic thrombocytopenic purpura treated with rituximab

Abstract

Rituximab may be used to treat patients with thrombotic thrombocytopenic purpura (TTP) refractory to plasma exchange or recurrent disease. While initial response rates are reported to be high, long-term follow-up data of patients treated with rituximab are not available to date however important to estimate the safety and benefit of this treatment. 12 patients with non-familial idiopathic TTP refractory to plasma exchange or with recurrent disease treated with rituximab between 2000 and 2008 were re-examined. The median follow-up was 49.6 months, ranging from 11 to 97 months. All patients achieved initial complete remission after application of rituximab. During follow-up, nine patients remained disease-free and three patients suffered from recurrent disease. All patients with recurrent disease responded to subsequent rituximab therapy. No long-term side effects were noted during the follow-up period. In conclusion, rituximab represents an effective second-line treatment option in relapsing or refractory TTP. Still, patients need to be closely monitored for relapses with extended follow-up.Response to Reviewers: Reviewer #11. Abstract, line 2: I think "acceptable" is not appropriate until larger studies are done. I would suggest changing to: "Rituximab may be used to treat relapsed or refractory TTP" Changes were made accordingly. 2.Abstract, line 5: While initial response rates are "reported to be" high..Changes were made accordingly.3. Abstract, line 32: "Still, patients need to be closely monitored as the relapse rate increases with longer follow-up." Change to ".monitored for relapses with extended follow-up".Changes were made accordingly. 4.Introduction, line 41: Remove "not otherwise explained"Changes were made accordingly. 5.Introduction, line 51: Revise: "Acquired idiopathic TTP is differentiated from hereditary TTP (Upshaw-Schulman syndrome)." ie how are they differentiated?The differentiation between acquired and congenital TTP follows in detail in the next paragraph: "Large progress was made in recent years in understanding the pathophysiology of TTP. Moake et al. described unusually large von Willebrand factor (VWF) multimers in the plasma of patients with relapsing acquired or congenital TTP causing intravascular platelet aggregation occluding the microvasculature [2]. Tsai et al. [3] and Furlan et al. [4] independently identified a VWF-cleaving protease (ADAMTS13) missing from the plasma of patients with congenital TTP [5] and severely deficient in patients with acquired idiopathic TTP. Mutations in the ADAMTS13 gene were shown to cause congenital TTP [6], whereas IgG autoantibodies inhibit the enzyme in most cases of the acquired form of the disease [7][8]." To avoid repetitions we left this part of the introduction as it was. If the editor has a distinct opinion to this point, we are more than willing to change it. 6.Introduction, line 12 (2nd page of introduction) and throughout the paper: "plasma exchange against fresh frozen plasma" change to ". WITH fresh frozen plasma."Changes w...

Thrombotic Thrombocytopenic Purpura: Etiopathogenesis, Diagnostics and Basic Principles of Treatment

“…An observational study that compared 21 patients with refractory TTP treated with rituximab and 53 historical controls treated with conventional therapy reported that all the patients treated with rituximab experienced platelet count recovery within 35 days compared to only 78% of the control patients (46). The results from 5 other similar studies showed that 83-100% rituximabtreated patients achieved complete remission (47)(48)(49)(50)(51)(52). The relapse rates after rituximab treatment ranged from 0% with a median follow-up of 10 months (47) to 33% with a median follow-up of 73 months (52).…”

Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura

“…However, ADAMTS13 recovery after preemptive rituximab administration was not sustained in up to 30% of patients, 14 and 1 or multiple additional severe drops of ADAMTS13 activity were observed in such patients, typically 18 to 24 months after rituximab administration, as a consequence of peripheral B-cell reconstitution. 24 Interestingly, these patients responded to further rituximab therapy.…”

“…8 Consequently, it is important to determine whether preemptive treatment (ie, after remission) with rituximab to deplete anti-ADAMTS13 antibodies could prevent long-term relapses. The encouraging results provided by preliminary studies [9][10][11][12][13][14][15][16][17][18] and the recommendations issued by our group led to the approval in France of rituximab for compassionate use in patients with acquired TTP and persistent severe ADAMTS13 deficiency. To ensure that all patients who received rituximab for TTP would be treated optimally and that their data would be collected in a standardized manner, our group developed recommendations for rituximab administration and for monitoring the biological response to the treatment.…”

How I treat refractory thrombotic thrombocytopenic purpura

“…[34][35][36][37] Most of the data are based on case reports and case series where rituximab was used concomitantly with other immunosuppressive agents. 23,34,[36][37][38][39][40][41][42] A recent thoughtful review on this topic adds some clarity to its use in this clinical situation. 43 In several case series, treatment of acute refractory and/or relapsing TTP with rituximab alone resulted in clinical remission in 87% to 100% of patients, and platelet recovery within a median of 11 to 14 days after the first dose.…”