title: HLA-identical sibling donor bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: influence of GVHD prophylaxis on outcome.
abstract: We have analysed the results of treating 140 consecutive patients with chronic myeloid leukaemia (CML) in chronic phase by bone marrow transplantation (BMT) using marrow from HLA-identical siblings performed between February 1981 and July 1991. Three different regimens were used sequentially to prevent graft-versus-host disease (GVHD): cyclosporin A (CsA) alone (n = 39), T-cell depletion of donor marrow (n = 51) and CsA with methotrexate (MTX) (n = 50). Eighty-four patients (61%) survive at a median of 49 months from BMT (range 3-120). The actuarial overall and leukaemia-free survivals at 5 years were 52% and 41% respectively. The actuarial probabilities of leukaemia-free survival and haematological relapse at 2 years for the CsA only group were 65% and 4%, for the T-cell depletion group 40% and 41% and for the CsA/MTX group 68% and 6% respectively. For the T-cell depletion group the probability of leukaemia-free survival was significantly lower (P less than 0.001) and the probability of relapse significantly higher (P less than 0.001) than for other methods of GVHD prophylaxis; differences between the other two groups were not significant. Previous reports that T-cell depletion with Campath-1M results in a high rate of relapse are confirmed. Patients in the CsA/MTX group have been monitored with cytogenetic and polymerase chain reaction studies for residual BCR/ABL transcripts. We conclude that the combination of CsA/MTX is currently the best available approach to prevention of GVHD after BMT for CML and in our hands it is not associated with a major risk of relapse.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.forename: R
authors.initials: R
authors.lastname: Szydlo
authors.forename: S
authors.initials: S
authors.lastname: Kelly
authors.forename: J O
authors.initials: JO
authors.lastname: Cullis
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
authors.forename: J
authors.initials: J
authors.lastname: Apperley
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
authors.forename: J M
authors.initials: JM
authors.lastname: Hows
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D006680:HLA Antigens; D012333:RNA, Messenger; D016572:Cyclosporine; D016044:Fusion Proteins, bcr-abl; D008727:Methotrexate