HLA-identical sibling donor bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: influence of GVHD prophylaxis on outcome.
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.
Marks
D I
DI
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Hughes
T P
TP
Szydlo
R
R
Kelly
S
S
Cullis
J O
JO
Schwarer
A P
AP
Mackinnon
S
S
Apperley
J
J
Barrett
A J
AJ
Hows
J M
JM
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
D004273:DNA, Neoplasm; D006680:HLA Antigens; D012333:RNA, Messenger; D016572:Cyclosporine; D016044:Fusion Proteins, bcr-abl; D008727:Methotrexate