Short- and long-term effects of rituximab for the treatment of thrombotic thrombocytopenic purpura: four case reports

Abstract

We report four cases of thrombotic thrombocytopenic purpura (TTP) successfully treated with rituximab in combination with plasma exchange and other immunosuppressive agents. All four cases fulfilled the diagnostic criteria of TTP with severe deficiencies in ADAMTS13 activity and a detectable anti-ADAMTS13 inhibitor. Four weekly doses of 375 mg/m(2) rituximab were initiated on day 3-29 of presentation as a salvage treatment for relapsing/refractory disease in three patients and as a first-line treatment in one. Resolution of clinical symptoms and hematological abnormalities occurred as early as the second dose and, after the completion of treatment, all four patients achieved complete response (CR). They are currently free from relapse and the duration of CR has been 13-72 months. During the treatment course, the level of ADAMTS13 activity and the titer of the inhibitor correlated well with resolution or exacerbation of the disease. This report suggests that rituximab exhibits short- and long-term favorable effects for the treatment of TTP and that a severe ADAMTS13 deficiency and ADAMTS13 inhibitor positivity may support early administration of rituximab in both acute/refractory and relapsing cases.

Rituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura

“…There are few severe adverse effects of RTX in treatment of the early stage of aTTP, 19 which was confirmed in our study. Humoral immune function due to depletion of B lymphocytes and consequent probable infection should be carefully examined in the long term after use of a standard dose of RTX.…”

“…There are few severe adverse effects of RTX in treatment of the early stage of aTTP, 19 which was confirmed in our study.…”

The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs

“…Acute TTP remains a life-threatening disease, leaving survivors of an acute bout at a high risk of relapse. 3 Treatment of frequently relapsing or refractory acquired TTP has remained challenging and consists of supplementing plasma exchange (PEX) with adjuvant immunosuppressive agents including in more and more cases the chimeric anti-CD20 monoclonal antibody rituximab, [4][5][6][7][8][9][10] known to efficiently deplete B cells in the circulation. Plasma cells, however, are not eliminated due to their low or lacking CD20 expression, 11,12 and long-lived memory B cells (CD20 1 ) have been postulated to hide in lymph organs, because antibody titers specific for tetanus, pneumococcal polysaccharides, and measles have remained generally unchanged after rituximab treatment.…”

Acquired thrombotic thrombocytopenic purpura

“…The most widely used substance is rituximab , a potent B-cell depleting chimeric IgG 1 mAb specific for CD20. CD20 is expressed on B-cells from the pre-B-cell to the pre-plasma-cell stage (40)(41)(42)(43)(44)(45)(46)(47). Depletion is believed to happen through antibody-dependent cell-mediated cytotoxicity (ADCC) (48), followed by complementmediated lysis and apoptosis of the CD20 + B-cells (49)(50)(51).…”