Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein that consists of the
extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to
the Fcof IgG1. Alefacept is produced by recombinant DNA technology in a Chinese Hamster Ovary
(CHO) mammalian cell expression system. It was shown to interfere with lymphocyte activation.
Alefacept was evaluated in two randomized, double-blind, placebo-controlled studies in adults
with chronic plaque psoriasis. Each course consisted of once-weekly administration for 12
weeks of placebo or alefacept. The response to alefacept was significantly better in both
studies. In both studies, onset of response to alefacept treatment (defined as at least 50%
reduction of baseline Psoriasis Area and Severity Index (PASI)) began 60 days after the start
of therapy. With one course of therapy, the median duration of response (defined as
maintenance of a 75% or greater reduction in PASI) was 3.5 months for alefacept treated
patients and 1 month for placebo-treated patients. Most patients who had responded to either
alefacept or placebo maintained a 50% or greater reduction in PASI through the 3-month
observation period.
Graft versus host disease (GVHD) is the most ominous side effect of allogenic stem cell
transplantation (SCT). It causes severe inflammatory process, which is usually located to the
skin, gut and liver. Treatment of GVHD consists of various immuno-suppressive and
immuno-modulating drugs, including steroids, cyclosporine, tacrolimus, methotrexate etc.
These drugs unfortunately can also cause severe immunologic failure that makes the patient
prone to infection and malignancy, and other medication-specific side effects. In spite of
this effect on the immune system, not all of the patients achieve control of GVHD, which
usually rapidly leads to death. Despite the use of innovative immunosuppressive modalities,
the prognosis of steroid resistant GVHD is usually poor. In the following study we will
evaluate the effect of alefacept on steroid unresponsive cGVHD.