Summary:The purpose of this study was to evaluate the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen (RIST) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In all, 36 patients (median age 55 years) underwent RIST from an HLA-matched related donor between September 1999 and December 2002. The diagnoses included AML (n ¼ 14), leukemia evolving from MDS (n ¼ 10), and MDS (refractory anemia with excess blasts n ¼ 6, refractory anemia n ¼ 6). The RIST regimen consisted of purine analog (cladribine or fludarabine)/busulfan, with or without antithymocyte globulin. The regimen was well tolerated, and 34 patients achieved durable engraftment and most achieved remission after RIST. A total of 17 patients developed grade II-IV acute GVHD, and 27 developed chronic GVHD. Eight patients relapsed, and five of them received antithymocyte globulin (ATG) as part of the preparative regimen. A total of 12 patients died (four disease progression, six transplantation-related complications, and two others). Estimated 1-year disease-free survival (DFS) in low-and highrisk groups was 85 and 64%, respectively. We conclude that RIST can be performed safely in elderly patients with myeloid malignancies, and has therapeutic potential for those who fail conventional chemotherapy. In view of the significant association between GVHD or ATG and DFS, defined management of GVHD following RIST should become a major target of clinical research.

Summary:A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reducedintensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graftversus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment. Bone Marrow Transplantation (2003) 32, 439-442. doi:10.1038/sj.bmt.1704146 Keywords: reduced-intensity stem cell transplantation; psoriasis; graft-versus-autoimmunity effect; graft-versushost disease Autologous stem cell transplantation (auto-SCT) has attracted attention for the treatment of severe lifethreatening autoimmune diseases, which include a stem cell disorder as a component. The background concept is that ablation of the diseased immune system followed by hematopoietic reconstitution with self-stem cells should restore normal immunity without attacking self-epitopes. Long-term remission and improvement have been observed in some cases after auto-SCT against autoimmune diseases. 1-6 Although auto-SCT has fewer toxicities and complications than allo-SCT, it is limited by the common recurrence of the primary diseases, especially in recipients of unmanipulated autografts. On the other hand, allo-SCT has been used to treat fatal disorders, both malignant and nonmalignant, as a curative approach. Theoretical graftversus-autoimmunity (GVA) effects due to the activation and reconstitution of donor T cells also support the effectiveness of allo-SCT against autoimmune diseases. 2,7 However, its significant treatment-related mortality has limited its application to life-threatening cases.Reduced-intensity stem cell transplantation (RIST), a new transplantation method with nonmyeloablative preparative regimens, has been developed to reduce regimenrelated toxicity (RRT) without spoiling the antitumor effect of allo-SCT. 8 The safety and efficacy of RIST have been demonstrated at our institution, with a 1-ye...