Reduced intensity conditioning regimens Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor E Kusumi 1 , M Kami 2 , K Yuji 1 , T Hamaki 2 , N Murashige 2 , A Hori 2 , R Kojima 2 , Y Kishi 2 , S-W Kim 2 , J Ueyama 1 , S Miyakoshi 1 , R Tanosaki 2 , S Morinaga 1 , S Mori 2 , Y Heike 2 , Y Muto 1 , S Masuo 3 , S Taniguchi 1 , Y Takaue 2 , for the Tokyo SCT Consortium 1 Department of Hematology, Toranomon Hospital, Tokyo, Japan; 2 Hematopoietic Stem Cell Transplantation Unit, The National Ca PRer Center Hospital, Tokyo, Japan; and 3 Department of Rheumatology and Hematology, The JR Tokyo General Hospital, Tokyo, Japan Summary: To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludar- abine-based (150–180 mg/m 2 , n ¼ 18) or cladribine-based (0.77 mg/kg, n ¼ 2). To enhance engraftment, antithymo- cyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclospor- ine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment- related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II–IV acute GVHD, and seven of 13 patients who survived 4100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P ¼ 0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients. Bone Marrow Transplantation (2004) 33, 697–702. doi:10.1038/sj.bmt.1704425 Published online 2 February 2004 Keywords: RIST; matched unrelated donors; antithymo- cyte globulin; intermediate-dose TBI Allogeneic hematopoietic stem cell transplantation (allo- HSCT) is the treatment of choice for patients with refractory hematological malignancies; however, it has been restricted to young patients without comorbidity. The introduction of reduced intensity stem cell transplanta- tion (RIST) has expanded the treatment option to older, medically infirm patients. 1,2 Another limitation of the treatment is the stem cell source; HLA-matched related donors are available to only 30% of the patients who require this procedure. An HLA-matched unrelated donor (MUD) is an important alternative donor source. 3 The feasibility of RIST from a MUD has not been extensively studied, leaving an optimal conditioning regimen to be determined. As of October 2002, we had treated 191 patients with hematological diseases or solid tumors with RIST, 20 of whom underwent RIST with unrelated bone marrow (BM). This study retrospectively examined the feasibility of RIST from a MUD. Patients and methods Patients and donors We studied 20 consecutive patients who underwent RIST from a MUD following either antithymocyte globulin (ATG)- or total body irradiation (TBI)-containing con- ditioning regimens at the Tokyo Stem Cell Transplant Consortium between January 2000 and October 2002. They were eligible for RIST due to age 450 years and/or organ dysfunction. Of the 20 patients, 17 had high-risk hemato- logical malignancies (progressive diseases or those in 42nd remission) (Table 1). The other three patients were classified as having low-risk diseases. All of the patients and donors gave their written informed consent in accordance with the requirements of the Institutional Review Board. HLA typing and donor matching An HLA-A, -B, and -DR antigen-matched donor was sought through the Japan Marrow Donation Program (JMDP) as reported previously. 4 Alleles at HLA-A2, 26, -B39, 61, and 75, which are highly polymorphic in the Japanese population, 5 and DRB1 were routinely identified Received 8 February 2003; accepted 9 October 2003 Published online 2 February 2004 Correspondence: Dr M Kami, Hematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; E-mail: mkami@ncc.go.jp Bone Marrow Transplantation (2004) 33, 697–702 & 2004 Nature Publishing Group All rights reserved 0268-3369/04 $25.00 www.nature.com/bmt