Allogeneic stem cell transplantation in the myelodysplastic syndromes: interim results of outcome following reduced-intensity conditioning compared with standard preparative regimens Jane E. Parker, 1 Tariq Shafi, 1 Antonio Pagliuca, 1 Aleksandar Mijovic, 1 Stephen Devereux, 1 Mike Potter, 2 H. Grant Prentice, 2 Mamta Garg, 3 John A. Yin, 3 Jenny Byrne, 4 Nigel H. Russell 4 and Ghulam J. Mufti 1 1 Department of Haematological Medicine, Guy’s, King’s, Thomas’ School of Medicine, 2 Department of Haematology, Royal Free and University College Medical School, London, 3 University Department of Haematology, Manchester Royal Infirmary, Manchester, 4 Division of Haematology, School of Clinical and Laboratory Sciences, University of Nottingham, Nottingham, UK Received 6 November 2001; accepted for publication 4 April 2002 Summary. Conventional allogeneic stem cell transplanta- tion (SCT) for myelodysplastic syndrome (MDS) is associated with excessive procedure-related mortality. The outcome following volunteer-unrelated donor (VUD) or sibling allogeneic SCT was therefore evaluated in 23 MDS patients conditioned with reduced-intensity regimens (fludarabine/ busulphan/Campath-1H) because of advanced age (48 vs 37 years, P ¼ 0Æ002) and/or co-morbidity (19 vs 3, P <0Æ0001) which precluded conventional transplanta- tion, and compared with 29 treated with standard protocols [busulphan/cyclophosphamide (Bu/Cy); Bu/Cy/total-body irradiation/Campath-1G]. Graft-versus-host disease (GVHD) prophylaxis comprised of cyclosporine/methotrexate. One hundred per cent donor engraftment (variable number tandem repeat analysis/cytogenetics/fluorescence in situ hybridization) was achieved in 18/19 (95%) evaluable patients receiving reduced-intensity regimens, although six (32%) have subsequently shown mixed chimaerism. Reduced-intensity conditioning was associated with signifi- cantly reduced duration of aplasia, less mucositis, fever, antibiotic, analgesia, parenteral nutrition use, less acute and chronic GVHD, and lower early procedure-related mortality [two (9%) vs nine (31%), P <0Æ05]. Six patients relapsed (two standard, four reduced-intensity) and two (reduced-intensity) experienced late graft failure. The 2 year actuarial overall/disease-free survival (OS/DFS) was 48/39% in the reduced-intensity arm and 44/44% in the standard group. The 2 year non-relapse mortality was 31% and 50% respectively. In VUD recipients, OS was superior in the reduced-intensity arm (49% vs 34%). Predictors of DFS included good/intermediate-risk karyotype, low/intermedi- ate-1 International Prognostic Scoring system score, human leucocyte antigen compatibility and attainment of complete remission. Our data demonstrates that VUD or sibling allogeneic SCT following reduced-intensity conditioning is feasible in high-risk MDS patients considered unsuitable for standard transplantation and is associated with comparable 3Æ5 year DFS to those receiving conventional regimens. Keywords: MDS, MDS-AML, allogeneic stem cell trans- plantation, reduced-intensity conditioning, Campath-1H. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective and dysplastic hae- mopoiesis. The natural history is variable, with approx- imately 50% of patients dying from cytopenic com- plications and 30% undergoing leukaemic transformation (Mufti & Galton, 1986; Greenberg et al, 1997). Growth factors and differentiation-inducing agents have been used in low-risk disease, with little evidence of prolongation or improvement in quality of survival (Aul et al, 1993; Greenberg et al, 1993; Wijermans et al, 2000). In high- risk cases, response to intensive chemotherapy is inferior to that observed in de novo acute myeloid leukaemia (AML), Correspondence: Professor Ghulam J. Mufti, The Department of Haematological Medicine, Guy’s, King’s, Thomas’ School of Medi- cine, Denmark Hill Campus, Bessemer Road, London SE5 8RX, UK. E-mail: ghulam.mufti@kcl.ac.uk British Journal of Haematology, 2002, 119, 144–154 144 Ó 2002 Blackwell Publishing Ltd