Five Years Update Results of Basiliximab (BAMAB) Therapy for Acute Refractory Graft Versus Host Disease (AGVHD).

The IL-2 activation of RAS pathway promotes lymphocyte proliferation, differentiation and development of A-GVHD. This mechanism can be inhibited by basiliximab, a chimeric murin-human monoclonal antibody which binds to the alpha chain of interleukin-2 receptors on activated T-cells. Basiliximab is already largely used to prevent acute rejection after renal transplantation, but the experience with this drug on BMT setting is still limited. We treated 34 patients (pts) with severe refractory A-GVHD with Basiliximab from december 1998 to october, 2003. Median age was 13 years (range: 2 to 38). Most of the patiens had received an unrelated BMT (73%). Cell source was bone marrow in 88% and cord blood in 12% of the patients. Diagnosis included acute leukemia (9 pts), MDS (4 pts), CML(9 pts), Fanconi anemia (9 pts), and SAA (3 pts). Because of a half life of about 7 days, BAMAB schedule was 40mg weekly for 2–3 doses (adults) and 20 weekly for 2–3 doses (children). All pts had a-GVHD grade III-IV, manifesting from day 6–248 after transplant (M: 24 d), while on cyclosporin, and refractory to association with steroids (2–5mg/kg/d). Skin was involved in 32, GI in 25 and liver in 23 patients. Median follow-up was 196 (range: 35–1847) days. Overall response rate was 82% (CR: 11 pts, PR: 17 pts). Two pts (8 %) were not evaluated due to early death. Response varied according to the site involved, being complete in 84% of skin, 48% of GI and 26% of liver GVHD. Duration of response varied from 5–1103 d (M: 38 d). There were no infusion-related reactions. Eleven pts are alive (32%), 7 pts with complete response, 3 with partial response and 1 pt without response. Acute GVHD reactivation was seen on 41% of the patients, but half of them could be rescued with other therapies (MMF, PUVA, steroids). Infection was the main cause of death, being responsible for 83% of all deaths (disseminated CMV-4 pts, fungal infection-6 pts and sepsis-8 pts). Other causes of death included bleeding (2pts) and relapse (2 pts). In conclusion, basiliximab was able to induce response on patients with refractory A-GVHD. Prospective studies with this drug are necessary to address the optimal dose, schedule and incidence of infection.