Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.
Yeshurun et al.·Biology of Blood and Marrow Transplantation
Klarer NutzenGRADEModerat81 Zitate
Stichproben = 48 Pat.
DauerMedian 16 Monate
Kontrolle101 historische Kontrollpatienten unter…
EndpunktAkute GVHD Grad II–IV
Verblindungoffen
DesignPhase-II-Studie (unkontrolliert mit historischen Kontrollen)
Cannabinoidcbd
Max. Dosis300.0 mg
Applikationoral
”Kernaussage
CBD zusätzlich zur Standardprophylaxe senkte die akute GVHD-Inzidenz signifikant gegenüber historischen Kontrollen (HR 0,3; p=0,0002).
Zusammenfassung
n=48 alloHCT-Patienten (79 % akute Leukämie/MDS), CBD 300 mg/Tag oral (Tag −7 bis +30) zusätzlich zu Standard-GVHD-Prophylaxe; kumulative Inzidenz akuter GVHD Grad II–IV bis Tag 100: 12,1 %, Grad III–IV: 5 %; kein Patient entwickelte akute GVHD während CBD-Einnahme. Hazard Ratio für Grad-II–IV-GVHD vs. 101 historische Kontrollen: HR=0,3 (p=0,0002). Non-Relapse-Mortalität Tag 100: 8,6 %; keine CBD-assoziierten UAW Grad 3–4.
InterventionCannabidiol (CBD) 300 mg/Tag oral, beginnend 7 Tage vor Transplantation bis Tag 30, zusätzlich zu Standard-GVHD-Prophylaxe (Cyclosporin + kurzes Methotrexat-Schema)
C
Kontrolle101 historische Kontrollpatienten unter Standard-GVHD-Prophylaxe
O
OutcomeKumulative Inzidenz akuter GVHD Grad II–IV bis Tag 100: 12,1%; Hazard Ratio für Grad II–IV akute GVHD vs. historische Kontrollen: 0,3 (p=0,0002)
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
Herabgestuft wegen
Ungenauigkeit
Qualitätsprofil
Größe★★★★★
VerblindungOffen
EffektstärkeKlarer Nutzen
Zitate / Jahr★★★★★
Autoren
Yeshurun M, Shpilberg O, Herscovici C, Shargian L, Dreyer J, Peck A, Israeli M, Levy-Assaraf M, Gruenewald T, Mechoulam R, Raanani P, Ram R.
Design: Phase-II-Studie (unkontrolliert mit historischen Kontrollen)
Teilen
Abstract
Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic 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 phase II study. 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. 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 myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were 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 grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse 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 incidences 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. (clinicaltrials.gov: NCT01385124).