Summary: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 ¼ 3), Fanconi's (n ¼ 3) and congenital (n ¼ 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. The long-term survival of aplastic anaemia (AA) with bone marrow transplantation (BMT) using HLA-identical family donors has improved over the years and is in the range of 75-90%. 1-3 However, in comparison, the survival of patients transplanted from unrelated donors has only been in the range of 20-50%. 2,4-6 Main causes of transplantation failure in unrelated donor transplants in patients with AA (acquired as well as Fanconi's anaemia) are a high-incidence of graft failure, toxicities related to conditioning regimen and graftversus-host disease (GVHD). 5,6 To improve the outcome of unrelated donor transplants, a multidimensional approach using strategies addressing all the above issues is needed.The optimum conditioning regimen for unrelated donor transplants in AA is not known. Excellent long-term outcomes have been reported with cyclophosphamide (CY) and antithymocyte globulin (ATG) in the conditioning of acquired AA patients using HLA-identical family donors. 3 However, a similar approach with unrelated donors resulted in a high-incidence of graft failure. 7 Irradiation containing regimens result in better engraftment, but add substantial regimen-related toxicity and more GVHD resulting in no improvement in survival. [8][9][10][11] The role of low-dose total body irradiation (TBI, 200-300 cGy) in acquired AA has also been investigated and recommended as a measure to reduce graft rejection. 12,13 Even with low-dose of TBI, fatal pulmonary toxicity such as diffuse alveolar damage has been observed. 12 Alemtuzumab (Campath-1H) is a humanized IgG1 anti-CD52 monoclonal antibody (MoAb) and effectively depletes lymphocytes. In a pilot study, we previously reported a low incidence of GVHD in marrow transplants from HLA-identical sibling donors u...