title: Marrow transplants from matched unrelated donors for aplastic anaemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning.
abstract: Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n=3), Fanconi's (n=3) and congenital (n=1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation.
authors.affiliation: Department of Cellular and Molecular Sciences, Division of Haematology, St George's Hospital and Medical School, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.forename: S E
authors.initials: SE
authors.lastname: Ball
authors.forename: D
authors.initials: D
authors.lastname: Sage
authors.forename: M
authors.initials: M
authors.lastname: Ortin
authors.forename: M
authors.initials: M
authors.lastname: Freires
authors.forename: E C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: J C W
authors.initials: JC
authors.lastname: Marsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000150:complications / Q000209:etiology / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D014019:Tissue Donors; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine