The B-cell compartment as the selective target for the treatment of immune thrombocytopenias

Francesco Zaja, Nicola Vianelli, Alessandra Sperotto, Salvatore De Vita, Isabella Iacona, Alfonso Zaccaria, Paola Masolini, Valentina Tomadini, Monica Tani, Anna Lia Molinari, Michele Baccarani, Renato Fanin

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells. Treatment with rituximab is associated with the development of a severe (even if transient) B-cell depletion from peripheral blood and lymphatic tissues. These effects could be useful in autoimmune diseases in order to interfere with the production of pathologic antibodies. Design and Methods. To investigate this, we treated 20 patients with rituximab 375 mg/m2 i.v. every 7 days for 4 times. These 20 patients all had active and symptomatic autoimmune thrombocytopenia that had relapsed or was refractory to standard therapies (15 had idiopathic thrombocytopenic purpura, 1 idiopathic thrombocytopenia and neutropenia, 2 thrombocytopenia and concomitant undifferentiated connective tissue disease, and 2 had thrombocytopenia and concomitant B-cell lymphoprolipherative disorders). Only treatment with steroids, if strictly necessary to maintain a safe number of platelets, was allowed during the period of rituximab administration, but only patients who reached steroid discontinuation (previously not possible) were considered responders. Results. Treatment was well tolerated and no acute or delayed toxic events were recorded. Rituximab proved to be active in 13/20 patients, with 9 complete and 4 partial responses. In 10/13 (77%) the response (platelet level > 50×109/L) was prompt, being achieved already after the first of the four planned infusions. After a median follow-up of 180 days (range: 60-480) 4 patients had relapsed. Age ≤ 60 years was correlated with a better response rate (p=0.03). No correlation was observed between response and gender, time from diagnosis to treatment (<12 vs > 12 months), total and CD20+ lymphocyte count, level of CD20 expression on B cells before the therapy and pharmacokinetics of the drug. Interpretation and Conclusions. Rituximab appears to be a promising immunotherapeutic agent for the treatment of autoimmune thrombocytopenias.

Original languageEnglish
Pages (from-to)538-546
Number of pages9
JournalHaematologica
Volume88
Issue number5
Publication statusPublished - May 1 2003

Keywords

  • B-cell depletion
  • CD20 intensity of expression
  • Immune thrombocytopenias
  • Rituximab
  • Rituximab pharmacokinetics

ASJC Scopus subject areas

  • Hematology

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