title: Favorable effect 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 anemia.
abstract: Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.
authors.affiliation: Department of Cellular and Molecular Sciences, Division of Haematology, St. George's Hospital and Medical School, London, UK. vikas.gupta@uhn.on.ca
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ball
authors.forename: Qi-long
authors.initials: QL
authors.lastname: Yi
authors.forename: Dedorah
authors.initials: D
authors.lastname: Sage
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McCann
authors.forename: Mark
authors.initials: M
authors.lastname: Lawler
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortin
authors.forename: Mylene
authors.initials: M
authors.lastname: Freires
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Hermann
authors.initials: H
authors.lastname: Waldmann
authors.forename: Edward C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Marsh
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000401:mortality / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D000074301:CD52 Antigen; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D003520:Cyclophosphamide