Associação entre os níveis plasmáticos de imatinibe e a resposta ao tratamento de leucemia mieloide crônica em pacientes de Manaus

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease that affects hematopoietic stem cells, which is characterized by the presence of Philadelphia chromosome, resulting from a balanced reciprocal translocation between arms 9 and 22 of ABL and BCR chromosomes, respectively. BCR-ABL gene acts on protein tyrosine kinases, driving cell proliferation of myeloid lineage, more specifically the granulocyte. Imatinib mesylate (MI) is the drug of choice for the treatment of this disease. However, although most of the results obtained with the therapy are excellent, some patients still show sub-optimal therapeutic response or still develop some type of resistance. Therefore, the aim of this study was to assess IM plasma levels in CML patients attended at a reference unit in Manaus and correlate them with variables that may interfere with these levels. Data collection consisted of a standardized questionnaire containing clinical information, socio-demographic, life habits, and use of other medications, as well as the use of Morisky Medication Adherence Scale questionnaire to estimate therapeutic adherence. Additionally, blood collection was performed to measure plasma concentration of the drug in the patient using HPLC-UV method. Molecular studies were performed to identify the presence of polymorphism in ABCG2 membrane transporter, which can influence the kinetic of the drug, decreasing its intracellular concentration. Among the results obtained, most patients were male, with a mean age of 52 years. After associating the clinical responses – hematological and molecular – with the plasma concentration obtained, there was a correlation between plasma concentration and major molecular response. Thus, patients who have RMM also have higher plasma concentrations of IM. Finally, it was concluded that therapeutic monitoring is a fundamental tool for optimal responses to the treatment, promoting necessary adjustments and contributing to patient survival.