Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease.
Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity following allogeneic bone marrow transplantation. Thalidomide is active in salvage therapy for high-risk or resistant CGVHD. In a prospective randomized trial, we tested initial therapy with thalidomide. Patients with extensive CGVHD were randomized to receive either cyclosporine and alternate-day prednisone (n = 27, no-thalidomide [no-thal] group) or cyclosporine, prednisone, and thalidomide (200-800 mg/day; n = 27, thal group). Although most patients responded, initial therapy with thalidomide did not improve control of CGVHD. Response rates were 83% versus 89% at 2 months (P = .7), 88% versus 84% at 6 months (P > .8) and 85% versus 73% at 1 year (P = .5) in the thal and no-thal groups, respectively. Multivariate analysis revealed related donor transplant (odds ratio [OR] = 11.3; P =.03) and de novo or quiescent onset of CGVHD (OR = 7.7; P =.04) to be significant predictors of good early response, whereas a platelet count of > or =100,000/microL was a significant predictor of good response (OR = 10.4; P =.04) at 1 year. Survival for the thal and no-thal groups was similar at 1 year (66% versus 74%) and 2 years (66% versus 54%, P = .85). Multivariate analysis revealed progressive onset CGVHD (relative risk [RR] = 4.2; P =.01), unrelated donor (RR = 5.7; P < .01), sex mismatch (RR = 7.9; P < .01), and platelet counts of <100,000/microL (RR = 3.8; P = .01) as significant predictors of poorer survival. These data suggest that despite a high response rate (79% response and 53% complete response) and encouraging survival rates (70% at 1 year and 60% at 2 years), thalidomide offers no clinical benefit when incorporated into initial therapy for CGVHD. The value of thalidomide as salvage therapy requires further study.
Arora
M
M
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Wagner
J E
JE
Davies
S M
SM
Blazar
B R
BR
Defor
T
T
Enright
H
H
Miller
W J
WJ
Weisdorf
D F
DF
D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007239:Infections / Q000209:etiology / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage*; D011379:Prognosis; D012307:Risk Factors; D016879:Salvage Therapy; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D013792:Thalidomide; D016572:Cyclosporine; D011241:Prednisone