Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT.
We conducted a prospective phase II study (NCT01385124). GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low dose anti-T-cell globulin (Fresenius). CBD 300 mg/day was given orally starting 7 days before transplantation until day 30.
Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or MDS and 35 patients (73%) were given a myeloablative conditioning. The donor was either an HLA-identical sibling (n=28), a 10/10 matched unrelated donor (n=16) or a one antigen mismatched unrelated donor (n=4). The median follow-up was 16 (range, 7-23) months. There were no grade 3-4 toxicities attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grade 2-4 and grade 3-4 acute GVHD by day 100 were 12.1% and 5%, respectively. Compared to 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grade 2-4 acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was 0.3 (p=0.0002). Rates of non-relapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidence of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively.
The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted.
Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
- [PubMed – as supplied by publisher]