Low incidence of acute graft-versus-host disease and recurrent leukaemia in patients undergoing allogeneic haemopoietic stem cell transplantation from sibling donors with methotrexate and dose-monitored cyclosporin A prophylaxis.
One of the major aims of allogeneic haemopoietic stem cell transplantation has been the effective suppression of graft-versus-host disease (GVHD) without loss of a graft-versus-leukaemia effect. For GVHD suppression, one of the most frequently used regimens has been the combination of cyclosporin (CsA) and a short course of methotrexate (MTX) although the optimal usage of these agents remains unclear. Here, we report the results of 55 patients with standard risk leukaemia who have undergone allogeneic transplantation using either bone marrow (n = 48) or G-CSF mobilised peripheral blood stem cells (n = 7) using CsA and MTX for GVHD prophylaxis where the dosage of CsA was regularly adjusted to maintain a trough whole blood level of 95-205 ng/ml for the first 50 days post-transplant. To achieve this level of CsA in the immediate post-transplant period, over 40% of patients required dose adjustments of CsA as a result of sub-therapeutic levels on day +1 post-transplant. The achievement of CsA levels within the therapeutic range was expedited following the introduction of a sliding scale for dose adjustment. With this regimen we have observed a low incidence of acute GVHD with only 11% of patients developing > or =grade II disease. With a median follow-up of 66 months (range 8-132) the probability of relapse is only 6.6%. The disease-free survival probability for all patients was 72% at 5 years. These results demonstrate that effective GVHD prevention with CsA and MTX can be achieved without a high risk of recurrent leukaemia provided that rapid attainment of therapeutic CsA levels is achieved and maintenance within a low therapeutic range may help to maximise this effect.
Department of Haematology, Nottingham City Hospital and University of Nottingham, UK.
J L
JL
Byrne
C
C
Stainer
H
H
Hyde
G
G
Miflin
A P
AP
Haynes
E M
EM
Bessell
N H
NH
Russell
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence; D014019:Tissue Donors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate