Haematologica, Vol 94, Issue 3, 443-444 doi:10.3324/haematol.2008.001396
Copyright © 2009 by Ferrata Storti Foundation
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kelly, K.
Right arrow Articles by Murphy, P. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelly, K.
Right arrow Articles by Murphy, P. T.

Letters to the Editor

Slow responses to standard dose rituximab in immune thrombocytopenic purpura

Kevin Kelly, Mary Gleeson, Philip Thomas Murphy

Department of Hematology, Beaumont Hospital, Dublin 9, Ireland

Correspondence: Philip Thomas Murphy, Department of Haematology, Beaumont Hospital, Beaumont, Dublin 9 Ireland. Phone: international + 353.1.8093000. Fax: international +353.1.8376982. E-mail:kevrkelly77{at}hotmail.com

Key words: platelets, immune thrombocytopenic purpura, disorders of platelet function.

We read with interest the article by Zaja et al. in which the results of a prospective multicenter Phase II study to assess the response rates of lower dose rituximab in adults with chronic immune thrombocytopenic purpura (ITP) were reported.1 In this single arm study 28 ITP patients received rituximab (100 mg/m2) weekly for four weeks. An overall response (platelet count >50x106/L) and complete response (platelet count >100x109/L) was achieved in 21/28 (75%) and 12/28 (43%) of patients, respectively. Interestingly the time to treatment response with lower dose rituximab was longer than in published studies with standard dose (375mg/m2 weekly for four weeks).2–4 The median time to a complete response was 44 days with a range of 7–90 days.

In a recent prospective Phase II study which assessed the efficacy of standard dose rituximab in chronic adult ITP patients, most patients who responded to rituximab did so early and none of the patients who failed to reach a platelet count of 50x109//L in two weeks achieved a good response at one year.2

In our center we have treated 11 patients (6 female and 5 male, mean age 50) with refractory chronic ITP with standard dose rituximab (375 mg/m2 weekly for four weeks) with similar response rates (6 patients reached a platelet count of >50x109/L, including 3 >100x109/L at six months) but we have noted that delayed responses to standard dose rituximab also occur (Figure 1). The best responses were seen in 2 female patients, aged 32 and 26 years, with baseline platelet counts of 4 and 25x109/L. Their platelet counts at one month were 87 and 84x109/L and at six months were 521 and 230x109/L, respectively without any further treatment. In fact in our experience, at one month, no patient had platelets > 100x109/L (Figure 1). In a systemic review, complete responses usually occurred 3–8 weeks after the first infusion of rituximab.5 However, our data show that delayed responses to standard dose rituximab can occur. These responses are unlikely to reflect spontaneous remission as this rarely occurs in adult chronic ITP.6


Figure 10940443
View larger version (26K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Response of chronic ITP patients over time, following first rituximab infusion. Complete response (CR), platelet count >100x109/L partial response (PR), platelet count 50–100x109/L. No response (NR). The arrows and overlying numbers represent patients changing response. Patients who required alternative treatment were classified as having no response.

Splenectomy has been considered standard second-line therapy for ITP.7 The response rate is about 65% but it is associated with a mortality of 0.2–1% and morbidity of 9.6–12.9% depending on the age of the patient and technique used.8 There is accumulating evidence that rituximab can be a safe and effective way to defer splenectomy particularly in younger patients.9 A lower dose rituximab regimen would result in considerable cost savings compared to a standard dose regimen and may be associated with less transfusion related reactions. While delayed responses may occur in the lower dose regimen they may also occur with standard dose rituximab. Since maximal response to both dosing regimens may be delayed, a decision regarding splenectomy should not be made until at least six months after rituximab therapy.

References

  1. Zaja F, Battista ML, Pirrotta MT, Palmieri S, Montagna M, Vianelli N, et al. Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica 2008;93:930-3.[Abstract/Free Full Text]
  2. Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood 2008;112:999-1004.[Abstract/Free Full Text]
  3. Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001;98:952-7.[Abstract/Free Full Text]
  4. Zaja F, Vianelli N, Battista M, Sperotto A, Patriarca F, Tomadini V, et al. Earlier administration of Rituximab allows higher rate of long-lasting response in adult patients with autoimmune thrombocytopenia. Exp Hematol 2006;34:571-2.[CrossRef][Web of Science][Medline]
  5. Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007;146:25-33.[Abstract/Free Full Text]
  6. Stasi R, Stipa E, Masi M, Cecconi M, Scimò MT, Oliva F, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med 1995;98:436-42.[CrossRef][Web of Science][Medline]
  7. Provan D, Newlan A, Norfolk D, Bolton-Maggs B, Lilleyman J, Greer I, et al. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003;120:574-96.[CrossRef][Web of Science][Medline]
  8. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004;104:2623-34.[Abstract/Free Full Text]
  9. Garvey B. Rituximab in the treatment of autoimmune haematological disorders. Br J Haematol 2008;141:149-69.[CrossRef][Web of Science][Medline]



This article has been cited by other articles:


Home page
 haematolHome page
F. Zaja and R. Fanin
Slow responses to standard dose rituximab in immune thrombocytopenic purpura. Author reply
Haematologica, March 1, 2009; 94(3): 444 - 445.
[Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kelly, K.
Right arrow Articles by Murphy, P. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelly, K.
Right arrow Articles by Murphy, P. T.