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

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 Edward Janik

Research output: Contribution to journalArticle

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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 withT-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 onTcells 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 depleteT- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.

Original languageEnglish (US)
Pages (from-to)2514-2522
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2009

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Human Herpesvirus 4
Monoclonal Antibodies
Natural Killer Cells
Neoplasms
B-Lymphocytes
Cell Count
Therapeutics
Antibodies, Monoclonal, Humanized
Natural Killer T-Cells
Stem Cell Transplantation
Immunosuppressive Agents
CD4 Lymphocyte Count
Bone Marrow Transplantation
siplizumab
Anti-Idiotypic Antibodies
Research Design
T-Lymphocytes
Incidence
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies. / O'Mahony, Deirdre; Morris, John C.; Stetler-Stevenson, Maryalice; Matthews, Helen; Brown, Margaret R.; Fleisher, Thomas; Pittaluga, Stefania; Raffeld, Mark; Albert, Paul S.; Reitsma, Dirk; Kaucic, Karen; Hammershaimb, Luz; Waldmann, Thomas A.; Janik, John Edward.

In: Clinical Cancer Research, Vol. 15, No. 7, 01.04.2009, p. 2514-2522.

Research output: Contribution to journalArticle

O'Mahony, D, Morris, JC, Stetler-Stevenson, M, Matthews, H, Brown, MR, Fleisher, T, Pittaluga, S, Raffeld, M, Albert, PS, Reitsma, D, Kaucic, K, Hammershaimb, L, Waldmann, TA & Janik, JE 2009, 'EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies', Clinical Cancer Research, vol. 15, no. 7, pp. 2514-2522. https://doi.org/10.1158/1078-0432.CCR-08-1254
O'Mahony, Deirdre ; Morris, John C. ; Stetler-Stevenson, Maryalice ; Matthews, Helen ; Brown, Margaret R. ; Fleisher, Thomas ; Pittaluga, Stefania ; Raffeld, Mark ; Albert, Paul S. ; Reitsma, Dirk ; Kaucic, Karen ; Hammershaimb, Luz ; Waldmann, Thomas A. ; Janik, John Edward. / EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 7. pp. 2514-2522.
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AU - O'Mahony, Deirdre

AU - Morris, John C.

AU - Stetler-Stevenson, Maryalice

AU - Matthews, Helen

AU - Brown, Margaret R.

AU - Fleisher, Thomas

AU - Pittaluga, Stefania

AU - Raffeld, Mark

AU - Albert, Paul S.

AU - Reitsma, Dirk

AU - Kaucic, Karen

AU - Hammershaimb, Luz

AU - Waldmann, Thomas A.

AU - Janik, John Edward

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N2 - 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 withT-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 onTcells 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 depleteT- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.

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