Efeitos adversos e resposta citogenética em pacientes com leucemia mieloide crônica tratados com imatinibe

Background: The treatment of chronic myeloid leukemia (CML) employs drugs known as tyrosine kinase inhibitors (TKIs). Comparative analyses of the effects of different TKIs has shown that these substances can reduce the immunogenicity of leukemic cells, and prejudice anti-tumoral immunity. Once the TKIs differ in terms of their direct influence on cells of the immunological system, the objective of this work was therefore to analyze alterations in the immunological systems of CML patients using different TKI drugs. Methodology/Principal findings:A review of the literature revealed that imatinib is considered to be the new paradigm for treatment of CML; however, use of this drug can result in inhibition of activation of immune system cells and development of resistance. Second and third generation TKIs can be used in the treatment of patients resistant to imatinib, but can have immunosuppressor effects. Nilotinib is more effective than imatinib in recently-diagnosed patients, however at high doses can induce myelosuppression and diminish cytokine production. Dasatinib was found to induce a rapid full cytogenetic response, with heightened in vivo immune-stimulation, in contrast to an immunosuppression observed in vitro. The mutated T315I phenotype of CML only shows a response to treatment with inhibitors that do not compete with ATP, involving aurora kinases that control mitosis, progression of the cellular cycle, and apoptosis induction. MK0457, which is able to act in the presence of the mutation, presents important bone marrow toxicity, while in small doses danusertib has shown anti-proliferative and pro-apoptotic activity against a wide spectrum of BCR-ABL-positive cells.Conclusions/Significance: Selection of the most suitable tyrosine kinase inhibitor in patients showing positive to the BCR-ABL mutation requires previous analysis of the phenotype and the influence of the TKI on the immunological system.

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“…Patients treated with imatinib can develop neutropenia, trobocytopenia, and anemia as adverse side-effects [9,12,14,15] .…”

Section: Imatinibmentioning

confidence: 99%

Immunological implications of the use of tyrosine kinase inhibitors in chronic myeloid leukemia

et al. 2012

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Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review

Sampaio

Santos

Marques

et al. 2021

WJCO

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly ― the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

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Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

Cid¹,

Magalhães²,

Quixadá³

et al. 2013

Revista Brasileira De Hematologia E Hemoterapia

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BackgroundIn the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. ObjectiveTo evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. MethodsThis retrospective study was based on information obtained from patients' records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC). All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. ResultsThe study population consisted of 100 patients who were mostly male (51%) with ages ranging between 21 and 40 years (42%), from the countryside (59%), in the chronic phase (95%), with high-risk prognostic factors (40%); the prognosis of high risk was not associated with complete hematologic response or complete cytogenetic response, but correlated to complete molecular response or major molecular response. Reticulin condensation was associated with complete hematologic response and complete cytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. The high adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. ConclusionSignificant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

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Efeitos adversos e resposta citogenética em pacientes com leucemia mieloide crônica tratados com imatinibe

Cited by 3 publications

References 24 publications

Immunological implications of the use of tyrosine kinase inhibitors in chronic myeloid leukemia

Immunological implications of the use of tyrosine kinase inhibitors in chronic myeloid leukemia

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

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