[ADHERENCE TO ORAL ANTI-CANCER DRUGS IN HEMATO-ONCOLOGY].

INTRODUCTION: Non-adherence to medical treatment is prevalent in the context of potentially life-saving treatment for diseases such as cancer. Estimates of non-adherence to oral anti-cancer therapy range between 27% and 63% in studies of cancer patients. This represents a growing challenge, due to the paradigm shift in anti-cancer treatment from parenteral chemotherapy to oral anti-cancer drugs. The importance of adherence to medical treatment is highlighted by the World Health Organization which considers non-adherence to be a major public health concern. Studies in several malignancies have shown an adverse effect of nonadherence on treatment response, survival and quality of life, accompanied by an increase in health-care related costs. The clinical vignette accompanying this review demonstrates the complexity of management of adherence to oral anticancer therapy, through an example of an elderly chronic myeloid leukemia patient, non-adherent to serial tyrosine kinase inhibitors (imatinib, dasatinib). Her non-adherence was explained by subtle socio-demographic, patient-related and treatment-related factors, which in hindsight could have already been identified at diagnosis, resulting in preemptive management of these barriers and adherence. Routine management by the hematologist, using education alone resulted in improvement of adherence, which was predictably short-lived. Our use of a multilevel and multidisciplinary adherence-enhancing intervention, incorporating feedback based on electronic monitoring of adherence, resulted in improved adherence and treatment response in this patient. This exemplifies the contemporary evidence-based approach to non-adherence to oral-anticancer therapy.

Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

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).

Nursing care for adolescents and young adults with cancer: literature review.

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.

Differences in Toxicity Between Ashkenazi and Sephardic Jews With Colon Cancer Treated With Adjuvant Chemotherapy: A Prospective Study.

BACKGROUND/AIM: Ethnicity of cancer patients is increasingly being recognized as an important factor that may influence intergroup variation in toxicity and efficacy of chemotherapy. Data from our institution suggested that differences in chemotherapy-associated toxicity are not limited to distanced ethnic subgroups, such as Caucasians, Afro-Americans, or Asians, but may exist even between two closely related Caucasian ethnic subgroups, such as Ashkenazi and Sephardic Jews. This study aimed to explore differences in severity and frequency of various side effects, including neurotoxicity between patients from the two Jewish subgroups receiving oxaliplatin-containing adjuvant chemotherapy for colon cancer (CC). PATIENTS AND METHODS: We recruited 75 patients, with performance status 0-1 and no background of neuropathy between 2012 and 2016. All patients completed a neurotoxicity questionnaire (NQ) and a QoL questionnaire (QoLQ) at baseline and the NQ also at each treatment cycle; during follow up, patients filled out the NQ and the QoLQ every four months for a total of one year. RESULTS: Of the 75 participants, 66 were evaluable for the study including 34 (52%) Sephardic and 32 (48%) Ashkenazi Jews. Grade ≥2 vomiting and diarrhea occurred more often in Sephardic than in Ashkenazi patients (p=0.008 and 0.012, respectively). Of the 66 evaluable patients, 11 (17%) developed grade 3 neurotoxicity; of these, 9 were Sephardic and 2 were Ashkenazi (p=0.028). There were no significant differences in the dynamics of QoL between both subgroups. CONCLUSION: Sephardic patients receiving oxaliplatin-containing regimens are at an increased risk for neurotoxicity and other side effects as compared to their Ashkenazi counterparts.

Surveillance of infectious complications in hemato-oncological patients.

BACKGROUND: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance. OBJECTIVES: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel. METHODS: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel. , RESULTS: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used. CONCLUSIONS: Hematology centers should monitor infection rates and report them in a uniform methodology.

Effect of Adherence-enhancing Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia (TAKE-IT): A Quasi-experimental Pre-Post Intervention Multicenter Pilot Study.

BACKGROUND: Nonadherence to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has been associated with inferior outcomes. Scarce evidence exists on the effectiveness of adherence-enhancing interventions. The present pilot study evaluated the feasibility and effectiveness of an intervention to improve TKI adherence in adult CML patients. PATIENTS AND METHODS: Using a quasi-experimental pre-post intervention design, we included a convenience sample of 58 CML patients (median age, 60.5 years; interquartile range, 19) receiving TKI treatment in 4 hematology institutes in Israel (median previous treatment duration, 34 months; interquartile range, 60). Of the 58 patients, 36 (62%) were receiving first-line treatment. TKI adherence was assessed using electronic monitoring for 7 months (4 months for the baseline assessment and for 3 months after the intervention) and defined as the percentage of days with dosing taken as prescribed. The multilevel intervention combined training of health care workers and multiple behavioral change techniques (eg, motivational interviewing, feedback on electronic monitoring printouts, behavioral change techniques tailored to reasons for nonadherence). The baseline and postintervention adherence were compared using generalized estimating equation models. RESULTS: The median baseline electronically monitored adherence (n = 55) was 97.5% (range, 48%-100%). The odds of taking the drug daily as prescribed were 58% greater after intervention (odds ratio, 1.58; 95% confidence interval [CI], 1.16-2.15). Adherence improved by only 1.5% overall (95% CI, 0.1%-2.8%) but by 8.5% (i.e. from 71.2% average adherence before intervention, to 79.6% after; P = .04) in a subgroup of 10 nonadherent patients (baseline adherence < 90%). CONCLUSION: TKI adherence improved with our pilot intervention, mainly in patients with suboptimal baseline adherence.

Identifying Tyrosine Kinase Inhibitor Nonadherence in Chronic Myeloid Leukemia: Subanalysis of TAKE-IT Pilot Study.

BACKGROUND: There are inconsistencies in reports on correlates for nonadherence (NA) to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). The diagnostic accuracy of subjective adherence measures using electronic monitoring (EM) as the reference standard is yet to be determined. This study aimed to evaluate correlates of TKI NA using EM and test the diagnostic accuracy of subjective adherence measures. PATIENTS AND METHODS: CML patients receiving a TKI for any duration were enrolled at 4 hematology institutes, and adherence was measured for 4 months. EM adherence was the reference adherence measure, expressed as the percentage of days with the drug taken as prescribed. Subjective adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) self-report and clinician-reported visual analog scale (VAS) at 2 time points. Baseline theory-derived correlates of NA were identified using single and multiple regression analysis. The diagnostic accuracy of BAASIS and clinician-reported VAS was tested against an exploratory EM NA cutoff of < 95%. RESULTS: The median EM adherence (n = 55) was 97.5% (range, 48-100%), while the 25th percentile was 92.1%. Lack of membership in a CML patient support group, living alone, and third-line treatment were associated with EM NA on multiple regression analysis. The BAASIS self-report (n = 94) had a sensitivity of 67% and a specificity of 71% for diagnosing NA, while clinician-reported VAS (n = 89) had a sensitivity of 78% and specificity of 42%. CONCLUSION: A quarter of patients had potentially clinically meaningful NA. These NA correlates and the BAASIS provide a basis for identifying nonadherent patients who can be targeted by interventions.

Tailoring the GVHD prophylaxis regimen according to transplantation associated toxicities-Substituting the 3rd dose of methotrexate to mycophenolate mofetil.

We hypothesized that in patients with early post allogeneic transplantation toxicities, the omission of the 3rd dose of methotrexate with concomitant starting of MMF would favorably affect complications. We found a higher incidence of grade 2-4 acute GVHD in patients given two doses methotrexate and MMF (n=31) compared to those given three courses of methotrexate (n=70) (p=.004), while grade 3-4 was similar. Other transplantation outcomes, including overall regimen-related-toxicity, were comparable. We conclude that tailoring the GVHD prophylaxis regimen may decrease the early post transplantation complications, however this come at the extent of a higher incidence of non-severe acute GVHD.