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Allogeneic stem cell transplantation in the myelodysplastic syndromes: interim results of outcome following reduced‐intensity conditioning compared with standard preparative regimens
Author(s) -
Parker Jane E.,
Shafi Tariq,
Pagliuca Antonio,
Mijovic Aleksandar,
Devereux Stephen,
Potter Mike,
Prentice H. Grant,
Garg Mamta,
Yin John A.,
Byrne Jenny,
Russell Nigel H.,
Mufti Ghulam J.
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03796.x
Subject(s) - medicine , mucositis , fludarabine , transplantation , busulfan , surgery , myelodysplastic syndromes , gastroenterology , methotrexate , total body irradiation , alemtuzumab , hematopoietic stem cell transplantation , cyclophosphamide , chemotherapy , bone marrow
Summary. Conventional allogeneic stem cell transplantation (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 = 0·002) and/or co‐morbidity (19 vs 3, P < 0·0001) which precluded conventional transplantation, 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 significantly 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 < 0·05]. 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/intermediate‐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 3·5 year DFS to those receiving conventional regimens.