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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).

Cancer patients belonging to the adolescent and young adult (AYA) age group have unique and very specific needs, which require special attention from the caring staff. The difficulty in maintaining the personal and professional development at this age is both natural and normal. Adding to this, coping with a life-threatening disease turns this stage in life into a period with many dilemmas and challenges of quite a complex nature. AYA patients have to deal with issues above and beyond the disease itself, which create a very complex coping picture. On top of that, prognosis for this age group has not improved in recent years, unlike the situation in other age groups like children and adults. The literature on this subject is extensive and comprehensive. However, most of the papers on this subject are very specific and narrow in their approach, each dealing with a specific topic. In this article, we bring together many different papers which make a wide and comprehensive picture of the subject of AYAs coping with cancer, coupled with recommendations for the caring staff. In this review we focus on the various aspects of the disease and treatments in AYAs, based on the conceptual model of quality of life proposed by Ferrell and colleagues [Cancer Nurs 1992;15:153-160; Cancer Nurs 1992;15:247-253], including physical, social, emotional and spiritual aspects. From the psychological standpoint, most of the papers discuss the negative aspects; however, in this article we try to include some articles from the positive psychology school of thought. From our findings it is apparent that there is an opportunity and need to further explore research in this regard. It is apparent that taking a unique approach to AYA cancer patients is needed in order to deal with the unique needs of this age group. This article aims at putting a framework around this issue, with actionable recommendations for the caring staff.

Introduction: Medication non-adherence (MNA) to tyrosine kinase inhibitors TKIs occurs in around 30% of chronic myeloid leukemia (CML) patients and is associated with adverse outcomes (Noens, 2009; Marin, 2010). Data on adherence-enhancing interventions (AEIs) in CML are scarce and an improvement in dose implementation has yet to be shown. Objective: To evaluate the efficacy of a multilevel AEI in improving MNA to TKIs in CML. Methods: We initiated a prospective multicenter (N=4) pre-post adherence intervention pilot study in CML (NCT01768689). Patients were eligible if they had received at least 3 months of imatinib, nilotinib or dasatinib for CML, irrespective of treatment line or subsequent duration. TKI adherence was assessed for 7.5 months using electronic monitoring (EM) with MEMS (Medical Events Monitoring System 6) and BAASIS. The MEMS bottle cap contains a micro-electronic circuit that registers dates and times of cap opening. The BAASIS is a 4-item patient reported outcome used to assess adherence in solid organ transplants and CML (Cleemput, 2007; Noens, 2009). We designed an investigational AEI to address known barriers to TKI adherence in CML (Figures 1 & 2), using components with proven efficacy in improving MNA in chronic diseases. The key elements were: behavioral change techniques (BCT); motivational interviewing (MI; Figure 2); and multilevel including patient (Figure 1), peer group and health care provider levels (not shown). The BCT taxonomy developed by Michie et al (Ann Behav Med, 2013) was used in Figures 1 & 2 to describe the intervention and to facilitate its reproducibility. During the first 4.5 months of adherence monitoring, MNA was managed as per local practice. The intervention phase was then initiated (Figure 1) and adherence measured for a further 3 months. The pre and post-intervention periods were defined as the 3 months before and after the initiation of the AEI, respectively. The primary outcome measure was EM adherence using MEMS, and primary analysis was the comparison between pre and post-intervention adherence, expressed as the percentage of days with drug taken as prescribed. Generalized Estimating Equation model was used to adjust for correlation between adherence levels pre and post intervention, measured in the same patient. We also explored the association between adherence according to BAASIS (at 3 different time-points during the pre/post intervention periods) and the corresponding 1-month periods of EM adherence. Results: Between 10/2013 and 7/2014, we enrolled 55 CML patients (median age, 60.5 years; median current TKI duration, 34 months) receiving imatinib (59%), nilotinib (18%) or dasatinib (23%). Median pre-intervention EM adherence was 97.5% (min 48%; 10th percentile: 82.6%; 25th: 92.1%; 75th: 99.3%; 90th: 100%; max 100%) and the mean was 93%. Non-membership in a CML patients group (51%), living alone (18%) and 3rd line treatment (9%) were each risk factors for pre-intervention MNA on multivariate analysis, whereby mean adherence was 7% (p<0.01), 10.2% (p=0.03) and 13.9% (p=0.01) lower than patients without each of these risk factors, respectively. The estimated mean adherence was near perfect (99.7%) with none of the above risk factors (N=21; 38%). The AEI affected a 1.45% improvement in adherence for the whole cohort (95% CI: 0.09-2.8%, p=0.04). The AEI led to an improvement of 2.51% in the non-members of a CML patient group (95% CI: 0.2-4.8%, p=0.03) relative to 0.25% (p=0.71) in the members. By extrapolation, this corresponds to an additional 5.3 days of correct intakes over 1 year for the whole cohort, and 9.5 days for non-members of a CML patient group. Using an exploratory cut-off of EM adherence ≥ 95% as adherent, the BAASIS (N=132) correctly classified 75.5% (74/98) as adherent and 73% (25/34) as non-adherent. Conclusion: The effect of the AEI is modest but statistically significant, and higher in non-members of a CML patients group. At the same time, this study shows the futility and potential resource wasting of trying to improve adherence in the large group of near-perfect adherers without risk factors. Our pilot study provides proof of concept that EM adherence may be improved in CML patients by a multilevel AEI, and that the magnitude of improvement is higher in subgroups at risk. These subgroups should be identified, if possible, by combining patient characteristics with the BAASIS. Disclosures Leader: Novartis: Research Funding. Sharf:Pfizer: Honoraria; BMS: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria, Research Funding; Ariad: Honoraria, Research Funding. Tousset:MWV Healthcare: Employment. Ellis:Novartis: Other: Advisory Board; Pfizer: Other: Advisory Board. Raanani:BMS: Other: Advisory Board; Pfizer: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; Ariad: Other: Advisory Board.

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