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Brief Communication: Rituximab in HIV-Associated Multicentric Castleman Disease

Mark Bower, PhD; Tom Powles, MD; Sarah Williams, MB; Tom Newsom Davis, PhD; Mark Atkins, PhD; Silvia Montoto, MD; Chloe Orkin, MD; Andy Webb, PhD; Martin Fisher, BSc; Mark Nelson, MA; Brian Gazzard, MD; Justin Stebbing, PhD; and Peter Kelleher, PhD
[+] Article and Author Information

From Imperial College, The Chelsea and Westminster Hospital, Barts and the London NHS Trust, and Queen Mary's University, London, and Royal Sussex Country Hospital, Brighton, United Kingdom.


Financial Support: Support for the cytokine assays was provided by St. Stephen's AIDS Trust, a national charity supporting clinical research in HIV/AIDS.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Mark Bower, PhD, Department of Oncology, The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom; e-mail, m.bower@imperial.ac.uk.

Current Author Addresses: Drs. Bower, Newsom Davis, Atkins, and Gazzard; Ms. Williams; and Mr. Nelson: The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.

Drs. Powles, Montoto, and Orkin: St. Bartholomew's Hospital, Little Brittain, London EC1 7BE, United Kingdom.

Dr. Webb and Mr. Fisher: Royal Sussex County Hospital, Eastern Road, Brighton BN1 3RP, United Kingdom.

Drs. Stebbing and Kelleher: Imperial College School of Medicine, 369 Fulham Road, London SW10 9NH, United Kingdom.

Author Contributions: Conception and design: M. Bower, T. Powles, T. Newsom Davis, C. Orkin, M. Nelson, B. Gazzard, J. Stebbing, P. Kelleher.

Analysis and interpretation of the data: M. Bower, T. Powles, S. Williams, T. Newsom Davis, S. Montoto, J. Stebbing, P. Kelleher.

Drafting of the article: M. Bower, T. Powles, S. Montoto, J. Stebbing, P. Kelleher.

Critical revision of the article for important intellectual content: M. Bower, T. Powles, M. Atkins, S. Montoto, A. Webb, M. Fisher, M. Nelson, J. Stebbing, P. Kelleher.

Final approval of the article: M. Bower, T. Powles, S. Williams, T. Newsom Davis, S. Montoto, C. Orkin, A. Webb, M. Fisher, M. Nelson, B. Gazzard, J. Stebbing.

Provision of study materials or patients: M. Bower, M. Atkins, S. Montoto, C. Orkin, A. Webb, M. Fisher, M. Nelson, P. Kelleher.

Statistical expertise: M. Bower, J. Stebbing.

Obtaining of funding: M. Nelson, B. Gazzard, P. Kelleher.

Administrative, technical, or logistic support: M. Bower, B. Gazzard, P. Kelleher.

Collection and assembly of data: M. Bower, M. Atkins, A. Webb, M. Fisher, J. Stebbing, P. Kelleher.


Ann Intern Med. 2007;147(12):836-839. doi:10.7326/0003-4819-147-12-200712180-00003
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Between 2003 and 2006, 21 patients (18 men) with multicentric Castleman disease were treated prospectively in a nonrandomized, open-label, phase II study with 4 infusions of rituximab at a standard dose of 375 mg per m2 of body surface area at weekly intervals. All biopsy specimens were reviewed and confirmed to be plasmablastic variants of multicentric Castleman disease with no microlymphoma, as defined by previous studies (1112). The plasmablasts showed immunoglobulin light chain restriction, were KSHV latent nuclear antigen–positive, and expressed CD20 on immunohistochemistry. Patients were recruited from 3 HIV and cancer centers, where local ethics review committees approved the study and patients gave informed consent. Toxicity was recorded at each visit and was graded by using the Common Terminology Criteria for Adverse Events, version 3.0 (13).

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Rituximab in HIV-Associated Multicentric Castleman Disease
Posted on March 12, 2008
Raphael Stricker
California Pacific Medical Center
Conflict of Interest: None Declared

The excellent clinical report by Bower and colleagues (1) demonstrates the efficacy of rituximab in HIV-associated multicentric Castleman disease. The main adverse reaction to this therapy was progression of Kaposi's sarcoma (KS) in 36% of patients. As noted by the authors, activation of human herpesvirus 8 (HHV-8), the viral agent associated with both KS and Castleman disease, appears to be mediated by two cytokines, IL-6 and IL-10 (2).

The authors measured cytokine levels in their patients before and after treatment with rituximab. The method of cytokine measurement was not described in the article. Only two cytokines showed a rebound pattern after initial suppression by rituximab: IL-6 and IL-10. It would be of interest to know whether this rebound was associated with progression of KS in individual patients. Cytokine levels might also be useful to predict response to rituximab in HIV-associated Castleman disease.

Raphael B. Stricker, MD California Pacific Medical Center San Francisco, CA 94108

References

1. Bower M, Powles T, Williams S, Davis TN, Atkins M, Montoto S, Orkin C, Webb A, Fisher M, Nelson M, Gazzard B, Stebbing J, Kelleher P. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann Intern Med 2007;147:836-9.

2. Oksenhendler E, Carcelain G, Aoki Y, Boulanger E, Maillard A, Clauvel JP, Agbalika F. High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients. Blood 2000;96:2069-73.

Conflict of Interest:

None declared

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