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A phase II/III randomized, multicenter trial of prednisone/sirolimus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft--host disease: BMT CTN 0801. Haematologica 2018 Nov;103(11):1915-1924 PMID: 29954931 PMCID: PMC6278959

Pubmed ID



Initial therapy of chronic graft--host disease is prednisone ± a calcineurin-inhibitor, but most patients respond inadequately. In a randomized, adaptive, phase II/III, multicenter trial we studied whether prednisone/sirolimus or prednisone/sirolimus/photopheresis was more effective than prednisone/sirolimus/calcineurin-inhibitor for treating chronic graft--host disease in treatment-naïve or early inadequate responders. Primary endpoints of this study were proportions of subjects alive without relapse or secondary therapy with 6-month complete or partial response in phase II, or with 2-year complete response in phase III. The prednisone/sirolimus/photopheresis arm closed prematurely because of slow accrual and the remaining two-drug three-drug study ended in phase II due to statistical futility with 138 evaluable subjects. The two-drug and three-drug arms did not differ in rates of 6-month complete or partial response (48.6% 50.0%, =0.87), or 2-year complete response (14.7% 15.5%, =0.90). Serum creatinine values >1.5 times baseline were less frequent in the calcineurin-inhibitor-free arm at 2 months (1.5% 11.7%, =0.025) and 6 months (7.8% 24.0%, =0.016). Higher adjusted Short Form-36 Physical Component Summary and Physical Functioning scores were seen in the two-drug arm at both 2 months (=0.02 and =0.04, respectively) and 6 months (=0.007 and =0.001, respectively). Failure-free survival and overall survival rates at 2 years were similar for patients in the the two-drug and three-drug arms (48.6% 46.2%, =0.78; 81.5% 74%, =0.28). Based on similar long-term outcomes, prednisone/sirolimus is a therapeutic alternative to prednisone/sirolimus/calcineurin-inhibitor for chronic graft--host disease, being easier to administer and better tolerated.

Author List

Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolaños-Meade J, Sarantopoulos S, Alousi AM, Abhyankar S, Waller EK, Mendizabal A, Zhu J, O'Brien KA, Lazaryan A, Wu J, Nemecek ER, Pavletic SZ, Cutler CS, Horowitz MM, Arora M, BMT CTN.


Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin


jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6