GVHD prophylaxis using low-dose cyclosporine improves survival in leukaemic recipients of HLA-identical sibling transplants.
Graft-versus-host disease (GVHD) prophylaxis of short duration (6 months) with low-dose cyclosporine A (CsA) starting at 1 mg/kg per day i.v. and four doses of methotrexate (MTX) were given to 171 consecutive leukaemic recipients of HLA-identical sibling transplants. In contrast, apart from MTX, retrospective controls received high-dose CsA, starting at 5-7.5 mg/kg per day i.v. and discontinued 1 yr post-transplant. In the low-dose CsA group, the probability of acute GVHD grades I-II (70% vs. 53%, P < 0.01), and chronic GVHD were increased (58% vs. 25%, P < 0.01), whereas the incidences of acute GVHD grades III-IV (9% vs. 5%, P = 0.62), and non-relapse mortality (20% vs. 22%, P = 0.58) were similar. Moreover, the probability of relapse was decreased (31% vs. 54%, P < 0.01), and both relapse-free (56% vs. 38%, P = 0.04) and overall survival (61% vs. 40%, P = 0.04) were markedly improved using the low-dose CsA regimen. In multivariate analyses, low-dose CsA was strongly associated with chronic GVHD [relative hazard (RH) 2.56, P < 0.01], which decreased the risk of relapse (RH 0.46, P < 0.01) and improved the probability of survival (RH 1.84, P < 0.01). In conclusion, a low-dose CsA regimen in leukaemic recipients of HLA-identical sibling transplants increases the rate of chronic GVHD, which seems to attenuate the risk of relapse, thereby improving patient survival owing to enhanced graft-versus-leukaemia effect.
Olsson
Richard
R
Centre for Allogeneic Stem Cell Transplantation, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden. richard.olsson@karolinska.se
Remberger
Mats
M
Hassan
Zuzana
Z
Omazic
Brigitta
B
Mattsson
Jonas
J
Ringdén
Olle
O
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D012189:Retrospective Studies; D035781:Siblings; D015996:Survival Rate; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate