This page contains a Flash digital edition of a book.
Long-term Efficacy of Rituximab Treatment in Thrombotic Thrombocytopenic Purpura

Table 1: Follow-up of 12 Patients Treated with Rituximab by Authors Case


Number (Years) 1 2 3 4 5 6 7 8 9

10 11 12

57 34 36 46 26 22 45 41 72 51 44 36

Sex Male

Female Female Female Female Male Male

Female Female Female Female Female

Prior TTP episodes

– – – 3 1 1 3 – – – 1 –

PE = plasma exchange; TTP = thrombotic thrombocytopenic purpura.

However, this data was based on a few patients with short follow-up, thus limiting the validity of the estimate. The higher relapse rate of 25% in our cohort is probably due to the longer follow-up period reported in the present study, and possibly reflects the gradual reversal of B-cell depletion and subsequent formation of new antibodies directed against ADAMTS13. Notably, from five patients suffering from partly frequent relapses before initiation of rituximab treatment, three have remained disease-free even after long-term follow-up. Only one patient relapsed after rituximab treatment during the initial TTP episode. All relapsing patients responded to subsequent rituximab therapy. Interestingly, the two patients treated with rituximab during the initial TTP episode, after stopping plasma exchange due to severe allergic reaction, had a sustained response without recurrence of TTP after a follow-up of 36 and 40 months. Both patients had not responded until the end of plasma exchange. Therefore, rituximab as a single agent is able to produce long-term remissions in TTP without continuous plasma exchange. However, the individual contribution of plasma exchange or rituximab to the treatment success remains open to question in the majority of patients. In two patients a maintenance therapy with rituximab was initiated consisting of 375mg/m2 every four weeks. One patient remains disease-free with ongoing maintenance therapy, the other is in sustained complete remission despite the cancellation of maintenance therapy after three months.

about 10%.13,14,26

Treatment of Further Relapse after Rituximab Treatment

and rituximab maintenance may be an option in these patients. However, this has to be weighed against potential long-term side effects, such as progressive multifocal leucoencephalopathy.39

Treatment decision-making in the case of further relapse after rituximab is difficult and not evidence-based. Rituximab has been used as pre-emptive treatment in patients with anti-ADAMTS13 auto- antibodies,38


alternative treatment would be a splenectomy, which is supported by data provided by Kappers-Klunne et al.40

Thirty-three patients with TTP

were retrospectively reported who were splectomised due to refractory or relapsing disease. After median follow-up of 109 months the 10-year relapse-free survival was 70%. As these data were generated without rituximab being a treatment alternative, one has to balance the risks of the operation procedure, post-operative complications and infectious complications post-splenectomy against the consequences of long-term B-cell depletion during rituximab maintenance therapy.


In our patient collective, no treatment-related, especially infectious, complications were reported. In all but two patients, B-cell counts had recovered at the end of follow-up, and one of these two patients is currently treated with rituximab maintenance therapy. This is congruent with previous reports using rituximab in relapsing or refractory TTP. Rituximab is usually well tolerated and acute reactions are usually mild without causing discontinuation of the drug.33 Infusion-related hypersensitivity adverse events including fever and hypotension are in most cases seen during the first infusion and mostly controlled with pre-medication and by slowing or temporary interruption of the infusion. However, rarely, potentially life- threatening complications have been reported. Progressive multifocal leukencephalopathy, a mostly fatal infection caused by the JC virus was described in lymphoma patients pre-treated with rituximab as well as in rare cases of immune-mediated disorders following rituximab treatment.41 cytomegalovirus42

or hepatitis B43 Cardiovascular events, delayed interstitial pneumonitis44

Other viral infections, such as reactivation of are more frequently reported. and renal

toxicity were also described following rituximab treatment. Especially when considering rituximab maintenance in frequently relapsing patients it is necessary to balance the risks and benefits of different treatment options. The risk of long-term B-cell depletion and the associated risk of potential infectious complications need to be weighed against the risks of complications associated with therapeutic plasma exchange including catheter thrombosis, infection of the venous access and transfusion reactions. The Oklahoma Registry group reports a 26% risk per patient for major complications of plasma exchange including a 2.8% fatality rate.45


Currently, data on rituximab treatment in refractory or relapsing TTP are based on case reports or smaller case series. Questions remain, such as timing of initiation of rituximab treatment, duration of treatment and treatment schedule and the schedule of concomitant therapeutic plasma exchange. With these limitations in mind, it appears that rituximab is an effective second-line treatment option for patients with idiopathic TTP, with some patients achieving sustained responses even after long-term follow-up. Prospective multicentre studies are required to determine whether rituximab can be safely used just as salvage therapy or even initially in addition to plasma exchange to decrease the relapse rate after first-line treatment.46,47

n 145 Reason for

Rituximab Initiation Allergy to PE Allergy to PE

Refractory to PE Relapse Relapse Relapse Relapse

Refractory to PE Refractory to PE Refractory to PE Relapse

Refractory to PE

Number of Rituximab Applications 375mg/m2

4 4 4 4 4 4 4 4 7 4 4 2

Follow-up (Months)

36 40 41 52 67 11 46 46 22 67 70 97

Relapse after Rituximab

– – – – 4 1 – – – – – 1

Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68