Alemtuzumab in the Treatment of Steroid Refractory Acute Graft-Versus-Host Disease.

Corticosteroids therapy is the mainstay of treatment for GVHD, however, it heavily impacts on post transplant morbidity and new modalities are continually needed. Alemtuzumab a humanized monoclonal antibody to CD52 has been used mainly as GVHD prophylaxis. Only a few patients have been treated with this antibody. From December 2004 to May 2006, we recruited 13 steroid refractory acute GvHD patients in a prospective trial evaluating the efficacy of alemtuzumab (Campath 1H) after exclusion of other severe HST-related complications. Primary endpoints were response to treatment after 14 and 28 days. Secondary endpoints were side effects and incidence of infectious complications. Treatment consisted of Campath 1H 10mg given s.c. on days 1–5. Median age was 33 years old (range:1–59) years, a fludarabine-based reduce intensive conditioning (RIC) regimen was used and the hematopoietic cells were obtained from HLA-identical siblings in 12 cases and one patient received stem cell from umbilical cord blood. All but one received CSA and MTX for GvHD prophylaxis. GvHD affected gut in 6 cases, skin in 3 liver in 4, and combination of gut and skin in 6 patients. In 6 of the 13 patients the clinical manifestations of GVHD were noticed after the first 100 days of HSCT. Complete resolution of GvHD, partial response and no response were seen respectively in 23%, 62% and 15%. Six over the 13 patients were able to decrease steroid use. Five patients developed CMV (pp65) reactivation and 3 of them were successfully treated with valganciclovir. All patients maintained complete chimerism during and after alemtuzumab therapy, and after a median follow-up of 4 months (range, 1– 17months), 8 remain alive, 3 without evidence of GVHD. Five patients died, 3 due to GvHD and the others due to infectious complications. This preliminary study suggests that alemtuzumab is a well-tolerated agent and has a beneficial effect in the treatment of refractory GvHD. It is only a pilot study and more studies are needed, but we suggest that this modality could be used early in the management of these patients in order to improve quality of life and reduce the long-term side effects of corticosteroids.