ORIGINAL ARTICLE Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia JR Passweg 1 , WS Pe´ rez 2 , M Eapen 2 , BM Camitta 3 , E Gluckman 4 , W Hinterberger 5 , JM Hows 6 , JCW Marsh 7 , R Pasquini 8 , H Schrezenmeier 9 , G Socie´ 4 , M-J Zhang 2 and C Bredeson 10 1 Department Innere Medizin, Kantonsspital, Basel, Switzerland; 2 Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA; 3 Medical College of Wisconsin, Milwaukee, WI, USA; 4 Hopital Saint Louis, Paris, France; 5 Donauspital, L. Boltzmann Institute STx, Vienna, Austria; 6 Southmead Hospital, Bristol, UK; 7 St George’s Hospital Medical School, London, UK; 8 Federal University of Parana, Curitiba, Brazil; 9 University of Ulm, Ulm, Germany and 10 CancerCare Manitoba, Winnipeg, Canada For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immuno- suppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor trans- plants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from 41-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, 41-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding prob- abilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplan- tation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor. Bone Marrow Transplantation (2006) 37, 641–649. doi:10.1038/sj.bmt.1705299; published online 20 February 2006 Keywords: severe aplastic anemia; alternative donor transplantation; overall survival Introduction Patients with acquired severe acquired aplastic anemia (SAA) were among the first to benefit from allogeneic bone marrow transplantation (BMT). In fact, the first clinical trials comparing transplant to non-transplant treatment was in patients with SAA receiving BMT vs androgens. 1,2 Bone marrow transplantation from an HLA-identical sibling is a well-established first-line treatment for young patients with SAA with excellent long-term results. 3–7 Imunosuppressive treatment with antithymocyte globulin and cyclosporine is an alternative therapy for patients without an HLA-matched related donor, patients with non-severe aplastic anemia, or older patients at higher risk of transplant-related morbidity and mortality. 8–10 Results of both treatment modalities are considered acceptable. Younger patients with severe neutropenia have better outcomes using an upfront transplant strategy and older patients and those with less severe disease are more likely to benefit from immunosuppression as first-line treatment, 9 since patients with severe neutropenia have a higher risk of infection-related deaths during nontransplant therapy while older patients are more likely to develop severe graft-versus-host disease (GVHD) after transplant- ation. Current practice guidelines do not recommend transplantation from an alternative donor as first-line treatment. 9–11 Transplantation from donors other than HLA-identical relatives can be successful, with first reports of unrelated donor transplantation dating back to the early 1970s. 12–16 There are relatively few studies focusing on alternative related or unrelated donor transplantation for SAA. 13,17–20 Probabilities of overall survival after unrelated donor transplant range from 29 to 50%, but most series are small with short follow-up. Information at the level of detail required for decision making, such as outcome of transplants from 1-antigen-mismatched siblings as a first- line treatment vs later in the disease course, outcome using relatives with more than one mismatch, unrelated donor transplantation as upfront vs salvage treatment with information on the degree of HLA-matching, is lacking. Received 23 September 2005; revised 8 December 2005; accepted 20 December 2005; published online 20 February 2006 Correspondence: Professor J Passweg, Department Innere Medizin, Kantonsspital, Petersgraben 4, Basel 4031, Switzerland. E-mail: jpassweg@uhbs.ch Bone Marrow Transplantation (2006) 37, 641–649 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt