An Observational study of Non-adherence in Patients with Chronic Myeloid Leukemia on Treatment with Imatinib – Prevalence, Predictors and Outcomes.

INTRODUCTION : Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that originates in an abnormal pluripotent bone marrow stem cell(1). It is consistently associated with a fusion gene, the BCR-ABL1, which is located on the Philadelphia chromosome. The Philadelphia chromosome is formed by the translocation t(9;22)(q34;11) – which results in juxtaposition of the ABL gene from Chromosome 9 to the BCR gene in Chromosome 22. This gene codes for a fusion protein (BCR-ABL) which has constitutive tyrosine kinase activity, resulting in uncontrolled myeloid proliferation. Although the major initial laboratory abnormality noted is usually neutrophilic leukocytosis, the BCR-ABL1 is found in all myeloid lineages as well as some lymphoid cells and endothelial cells. If untreated, CML will progress from an indolent chronic phase to a more aggressive accelerated phase or blast crisis. AIMS AND OBJECTIVES : Prevalence Estimation – To determine the prevalence and severity of non-adherence to Imatinib among CML patients in the month prior to interview; provided that these patients have been on treatment for at least 6 months. • Identification of Predictors of Non-Adherence – To identify those variables which are predictive of patient non-adherence. • Non-Adherer Analysis: To assess impact of non-adherence on outcome. • To assess patient-perceived adverse effects with Imatinib • To document degree of knowledge of disease. • To document the toxicity profile of imatinib in patients with CML. MATERIALS AND METHODS : The study is designed as an observational study in patients with chronic myeloid leukemia, who are currently under follow-up in the department of Hematology, CMC Hospital Vellore, during the period May 1st 2012 – July 31st 2012. All patients with CML on Imatinib Mesylate (Glivec / Veenat) for at least 6 months were included in the study. All patients were counseled about the study and informed consent was taken from all patients prior to enrollment. In case of minors (age <18years), assent forms were signed by one parent prior to enrollment. RESULTS : There were 454 patients eligible for study, of which 2 patients refused consent for participation, who did not wish to divulge information on compliance, despite assurances that it would have no bearing on the cost subsidy for therapy. Data was collected from the 452 patients who gave consent. The median age of presentation in this study was 42 years (range: 4-81). Children and adolescents comprised 3.7% of the study population, and patients above 60yrs of age comprised 8.5% of the population under study. There was a striking male predominance (67.5% versus 32.5%). The majority of patients had received only primary school education (47.5%), 21.4% had high school education and 27.6% were university educated. Fifteen patients (3.3%) were uneducated. CONCLUSION : 1. Non-compliance (3 missed doses per month) is seen in 8% of the population under study. 2. Non-compliance is a complex issue with some society-specific causes – such as frequent festivals, and practices of fasting. 3. University education is associated with higher rates of compliance. 4. Minor toxicities are commonly seen with imatinib, and in a small proportion of patients will translate to non-compliance with medication. 5. Rates of compliance may be improved by utilizing involving pharmacist/nurse involvement in patient care. 6. Non-compliance with daily dosing of Imatinib (>3 doses missed per month) is associated with a suboptimal cytogenetic response at 18months and suboptimal molecular responses at 24months. 7. Interphase FISH on peripheral blood is a practical method to assess cytogenetic response, and it correlates well with molecular response at 18months and 24months