Publication Date:
2007-11-16
Description:
Epstein Barr virus (EBV) has the capacity to transform B lymphocytes and in the setting of immunosuppression increases the risk of developing EBV induced lymphoproliferative disease (EBV LPD). This is a heterogeneous condition ranging from a benign polyclonal B cell proliferation to frank non-Hodgkin’s lymphoma. EBV LPD is associated with immunosuppressive agents used in solid organ, bone marrow and stem cell transplantation, and in certain congenital immunodeficiencies. We conducted a single institution phase I dose escalation study of siplizumab, a humanized monoclonal antibody to CD2, in patients with T-cell malignancies. A total of 29 patients (pts) were enrolled, of which 4 (13.7%) developed EBV LPD. In the original trial design (n=23) pts received escalating drug doses over 2 or 3 consecutive days per treatment week every 2 weeks (cohorts 1–7). In an attempt to increase the rate of drug delivery the trial was amended, for pts (n=6) to receive a single dose on day 0 and 14, and then once weekly thereafter (cohorts 8–10). While initial responses were exciting (2 complete responses, 7 partial responses and 10 stable disease) the development of EBV LPD was a concern. One of 23 (4.3%) pts in the original design and 3 of 6 (50%) in the revised schema developed EBV LPD within 6 months of starting therapy. The 29 pts included adult T-cell leukemia/lymphoma (n=15), large granular lymphocyte leukemia (n=7), cutaneous T-cell lymphoma (n=4) and peripheral T-cell lymphoma (n=3). A median of 2 (range 0–6) prior therapies and a median of 4 (range 1–26) courses of siplizumab with doses ranging from 0.4mg/kg to 4.8mg/kg were administered either biweekly or weekly depending on the cohort. Of the 4 EBV LPD cases, one responded to withdrawal of siplizumab, one to rituximab, another to combination chemotherapy and rituximab, and the remaining patient succumbed to a combination of her underlying disease and EBV-LPD. Review of T-cell trends in response to therapy demonstrated a reduction in the geometric mean of CD4 (84.9%, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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