Alefacept Treatment for Graft Vs. Host Disease May Not Suppress the Graft Vs. Leukemia Effect.

In general it is expected that strong immune suppression that alleviates GVHD, will increase the risk of relapse. Alefacept (Amevive®) is an immunosuppressive dimeric fusion protein that is used for psoriasis control. We showed its remarkable effect in acute steroid resistant/dependent and chronic extensive GVHD.

To date, 42 patients with a median age of 31.5 years (range 3-66) were treated by us with alefacept due to acute (n=28) or chronic (n=14) steroid resistant/dependent GVHD (27 males, 15 females). Twenty were transplanted from HLA matched family members, 14 from HLA matched unrelated donors, 8 from mismatched donors and 2 from unrelated cord blood units. Pretreatment acute GVHD grade ranged 2-4 (median 3) and involved the skin (30), gut (19) and liver (7). All the patients with chronic GVHD had extensive involvement prior to therapy.

The median time from transplantation to alefacept was 42.5 days and 13 months in acute and chronic GVHD respectively (range 18-110d and 3-47.5m) and a median of 9 (range 1-25) injections that were given per patient. Thirty-four out of the 41 evaluable patients (83%) responded to the treatment (23/28 and 11/13 in the acute and chronic group respectively). Despite this high response rate, demonstrating the deep immunosuppressive and immunomodulative effect of alefacept, only 5/41 evaluable patients (figure 1) have relapsed (with a median follow-up of 30.8 months on the 17 survivors). Other than the 5 patients that relapsed (all treated with calcineurin inhibitor and steroids), full-donor peripheral blood chimerism (100% donor cells and no residual host-type DNA) was stable throughout the treatment period and later in all but one patient, that developed mixed chimerism under alefacept treatment. His chimerism returned to full-donor chimerism with taper-down of immune suppression. Currently, 17/42 (40.5%) patients are alive (figure 1), most with improved or stable GVHD. Twenty-six patients died due to either: GVHD progression (n=14), progression of the basic disease (n=4), infections (n=5) or other causes (n=3).

Alefacept is effective and safe for the treatment of acute or chronic steroid resistant/dependent GVHD and may discriminate between GVHD and GVL.

No relevant conflicts of interest to declare.