EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies.

Abstract

PURPOSE:

We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.

EXPERIMENTAL DESIGN:

We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients with T-cell malignancies.

RESULTS:

Although initial responses were encouraging, 4 (13.7%) patients developed EBV-LPD and the trial was stopped. Reductions in CD4(+) and CD8(+) cell count numbers in response to therapy were seen in all patients, but in those patients developing EBV-LPD a significantly greater reduction in natural killer (NK) cell number and CD2 expression on T cells was seen. These findings highlight the importance of NK-cell depletion and CD2 expression in addition to T-cell depletion in the etiology of EBV-LPD.

CONCLUSIONS:

The emergence of EBV-LPD may be associated with the ability of siplizumab to deplete both T and NK cells without affecting B cells. Agents that deplete T- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.

• Authors: Deirdre O'Mahony, John C Morris, Maryalice Stetler-Stevenson, Helen Matthews, Margaret R Brown, Thomas Fleisher, Stefania Pittaluga, Mark Raffeld, Paul S Albert, Dirk Reitsma, Karen Kaucic, Luz Hammershaimb, Thomas A Waldmann, John E Janik
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 7 Pg. 2514-22 (Apr 01 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19293260 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Sialic Acid Binding Ig-like Lectin 2
• siplizumab

Topics

• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (adverse effects, therapeutic use)
• Epstein-Barr Virus Infections (immunology)
• Female
• Humans
• Leukemia, Large Granular Lymphocytic (complications, diagnosis, drug therapy)
• Leukemia-Lymphoma, Adult T-Cell (complications, diagnosis, drug therapy)
• Lymphocyte Depletion
• Lymphoproliferative Disorders (immunology)
• Male
• Middle Aged
• Positron-Emission Tomography
• Sialic Acid Binding Ig-like Lectin 2 (immunology, metabolism)
• Tomography, X-Ray Computed