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


METHODS
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.
O'Mahony
Deirdre
D
Metabolism Branch, Center for Cancer Research, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland and MedImmune, Inc, Gaithersburg, Maryland, USA.
Morris
John C
JC
Stetler-Stevenson
Maryalice
M
Matthews
Helen
H
Brown
Margaret R
MR
Fleisher
Thomas
T
Pittaluga
Stefania
S
Raffeld
Mark
M
Albert
Paul S
PS
Reitsma
Dirk
D
Kaucic
Karen
K
Hammershaimb
Luz
L
Waldmann
Thomas A
TA
Janik
John E
JE
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051918:Sialic Acid Binding Ig-like Lectin 2; C544394:siplizumab