Tyrosine kinase inhibitors in patients with chronic myelogeneous leukemia: defining the role of social risk factors and non-adherence to treatment.

OBJECTIVE: To assess the role of social risk factors on adherence to tyrosine kinase inhibitors (TKI) therapy in chronic myeloid leukemia (CML) patients. METHODS: This is a retrospective study and eligible patients were adults with CML on TKI treatment. Cases of no adherence to treatment were confirmed during pharmacists' consultation (patient-reported adherence). Baseline characteristics between groups were compared between cases and controls groups. Risk factors identified in bivariate analysis (p<0.2) were included in multivariate model. A qualitative investigation assessed whether such predictors of non-adherence had causal relationship. RESULTS: Of 151 patients with CML consulted by pharmacists, 21% had adherence problems. Despite patients with secondary school (p=0.03), most of investigated social risk factors did not differ between groups. However, by using a qualitative approach, patients' level of education could not explain low adherence rates behavior. CONCLUSIONS: Social determinants of health, herein investigated, were unlikely to predict adherence to treatment. Regression techniques may lead to untrue statements, so future researches should consider investigating the causes, not only the statistical estimates.

Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas / Chronic myeloid leukemia and other chronic myeloproliferative disorders

A leucemia mieloide crônica (LMC) é uma doença clonal da medula óssea caracterizada pela presença do cromossomo Philadelphia (Ph), resultante da translocação entre os cromossomos 9 e 22. O gene híbrido assim formado, BCR-ABL codifica proteínas com atividade de tirosinoquinases que regulam o crescimento celular. A partir da década de 80, o transplante alogênico de células-tronco hematopoéticas (TCTH) se tornou tratamento de escolha para pacientes com idade menor que 55 anos de idade e doador compatível. Não obstante, a partir do advento dos inibidores de tirosinoquinases, drogas de alta eficácia e baixa toxicidade, houve uma mudança no algoritmo de tratamento da LMC. As indicações do TCTH foram restritas em decorrência da mortalidade relacionada a este procedimento e o mesilato de imatinibe tornou-se o novo tratamento de escolha para esta enfermidade. No Brasil e possivelmente em outros países em desenvolvimento, as condições socioeconômicas fazem com que o TCTH ainda seja considerado como primeira linha de tratamento em algumas situações. O TCTH permanece indicado nas doenças (ou neoplasias) mieloproliferativas, como a mielofibrose primária em situações de alto risco e pacientes portadores de policitemia vera ou trombocitose essencial que tenham evoluído para mielofibrose com características de alto risco.

Chronic myeloid leukemia (CML) is a clonal disease of the bone marrow characterized by the presence of Philadelphia chromosome (Ph) which results from translocation between chromosome nine and 22. The hybrid gene, BCR-ABL, encodes proteins with tyrosine kinase activity that regulate cell growth. From the 80ïs allogeneic hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for patients younger than 55 years of age and donor. However, from the advent of tyrosine kinase inhibitors, drugs of high efficacy and low toxicity, there was a change in the treatment algorithm of CML. The indications of HSCT have been restricted as a result of mortality related to this procedure and imatinib mesylate has become the new treatment of choice for this disease. In Brazil and possibly in other developing countries, socio-economic conditions make HSCT still feasible as first-line treatment in some situations. The HSCT remains indicated for Ph negative myeloproliferative disorders such as high risk myelofibrosis or patients with polycythemia vera or essential thrombocytosis that have evolved to myelofibrosis with high-risk features.

O tratamento da Leucemia Mielóide Crônica com mesilato de imatinibe / Therapy of Chronic Myeloid Leukemia with imatinib mesylate

O mesilato de imatinibe é atualmente o tratamento de escolha para pacientes com Leucemia mielóide Crônica (LMC) recém-diagnosticados. Desde os primeiros estudos clínicos em 1998 até o estudo IRIS, que comparou o uso em primeira linha de imatinibe com interferon + ara-C, esta droga vem se consolidando em segurança e eficácia. Ainda há, entretanto questionamentos sobre a melhor dose inicial, a identificação dos pacientes que mais se beneficiariam e a melhor abordagem frente a respostas sub-ótimas e resistência. Os principais estudos clínicos publicados com mesilato de imatinibe são revisados no presente artigo, e discutidos sob a perspectiva da realidade brasileira.

Imatinib mesylate is currently the gold-standard therapy for patients with newly diagnosed Chronic Myelogenous Leukemia. From the clinical trials in 1998 to the IRIS study, which compared first line imatinib treatment with interferon and low dose ara-C, this drug has been consolidated in regards to its safety and efficacy. There are still some questions to answer. Which would be the best initial dose? Are there any patients who benefit more than others? What is the best approach to suboptimal response and resistance? The most important published clinical studies are reviewed in the current article and discussed from a Brazilian perspective.