Favourable Impact on Acute and Chronic Graft-Versus-Host Disease with Cyclophosphamide and In-Vivo Anti-Cd52 Monoclonal Antibodies for Marrow Transplantation from Hla-Identical Sibling Donors for Acquired Aplastic Anaemia.

Despite excellent long-term results of bone marrow transplantation (BMT) in acquired severe aplastic anemia (SAA), graft-versus-host disease (GVHD) continues to remain a major concern. Approximately 30–40% patients experience chronic GVHD resulting in long-term complications and impaired quality of life. At St. George's Hospital, we investigated the role of anti-CD52 monoclonal antibodies (MoAb) in transplant protocols for SAA. The CD52 antigen is expressed widely on virtually all lymphocytes including T and B-cells, NK cells, dendritic cells, eosinophils and macrophages but is absent from erythrocytes, platelets and marrow progenitors. Between Aug 1989 and Nov 2003, 33 patients at our centre with acquired SAA underwent BMT from HLA-identical sibling donors using cyclophosphamide (CY) 50 mg/kg x 4 (days −5 to −2) and anti-CD52 MoAb 0.75–1 mg/KgBW as conditioning. Prior to 1999, rat derived anti-CD52 MoAb (Campath-1G) was used. We switched to humanized version of anti-CD52 MoAb (Alemtuzumab) when it became available in 1999. Median age at BMT was 17 yrs (range 4–46). Prior to BMT, 58% were heavily transfused (>50 transfusions) and 42% had previously failed anti-thymocyte globulin (ATG) based immunosuppressive therapy. Unmanipulated bone marrow was used as source of stem cells in all except one. GVHD prophylaxis was with cyclosporine (CSA) alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to CSA. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 (24%) patients (primary,4; secondary, 4). Graft failure was non-significantly higher in heavily transfused patients and those receiving CSA and anti-CD52 MoAb as GVHD prophylaxis. Of those failing grafts, 4 survived long-term (complete autologous recovery, 2; autotransplant from previous stored marrow, 1; second allograft, 1). Acute grade II-IV GVHD and chronic GVHD was seen in 13% and 4%, respectively. None developed extensive chronic GVHD. Of the 19 recipients positive for cytomegalovirus (CMV), reactivation was seen in 5(26%) with in 100 days. No cases of late CMV reactivation were observed. Six patients died of complications related to BMT at a median of 248 days (range 47–414). With a median follow-up of 59 months, the 5-year survival was 81% (95% C.I. 68–96). There was a non-significant trend towards improved survival in patients transplanted after 1995 (93% vs. 74%). The performance status of all survivors is 100% except one who developed avascular necrosis of hip.