TY - JOUR
T1 - EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies
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
PY - 2009/4/1
Y1 - 2009/4/1
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.
AB - 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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U2 - 10.1158/1078-0432.CCR-08-1254
DO - 10.1158/1078-0432.CCR-08-1254
M3 - Article
C2 - 19293260
AN - SCOPUS:65249094237
SN - 1078-0432
VL - 15
SP - 2514
EP - 2522
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -