Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?
One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.
Storb
R
R
Divisions of Clinical Research, Fred Hutchinson Cancer Research Center; Seattle, WA 98104, USA.
Leisenring
W
W
Anasetti
C
C
Appelbaum
F R
FR
Deeg
H J
HJ
Doney
K
K
Martin
P
P
Sullivan
K M
KM
Witherspoon
R
R
Pettinger
M
M
Bensinger
W
W
Buckner
C D
CD
Clift
R
R
Flowers
M E
ME
Hansen
J A
JA
Pepe
M
M
Chauncey
T
T
Sanders
J
J
Thomas
E D
ED
D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D017567:Karnofsky Performance Status; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D015999:Multivariate Analysis; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D019172:Transplantation Conditioning; D017211:Treatment Failure
D016572:Cyclosporine; D008727:Methotrexate