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OBJECTIVE: The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia. METHODS: A retrospective review was performed of 100 non-electronic records of patients with Ph(+) chronic myeloid leukemia treated with imatinib mesylate. The study period was from January 2001 to January2011. Data were analyzed by Chi-Square and Correspondence analysis using the Statistical Analysis System software package. RESULTS: At the beginning of treatment 41% of patients were in advanced stages of the disease. The unavailability of the drug (44.8%) and myelotoxicity (25.7%) were the most frequent reasons for interruption. The adherence rate was < 90% in 47% of the cases. The low adherence influenced the cytogenetic response (p-value = 0.020) and molecular response (p-value = 0.001). Very high adherence (> 95%) induced complete cytogenetic response, major cytogenetic response and major molecular response. CONCLUSION: The population of this study obtained lower-than-expected therapeutic responses compared to other studies.

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Objetive: The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia. Methods: A retrospective review was performed of 100 non-electronic records of patients with Ph+ chronic myeloid leukemia treated with imatinib mesylate. The study period was from January 2001 to January2011. Data were analyzed by Chi-Square and Correspondence analysis using the Statistical Analysis System software package. Results: At the beginning of treatment 41% of patients were in advanced stages of the disease. The unavailability of the drug (44.8%) and myelotoxicity (25.7%) were the most frequent reasons for interruption. The adherence rate was < 90% in 47% of the cases. The low adherence influenced the cytogenetic response (p-value = 0.020) and molecular response (p-value = 0.001). Very high adherence (> 95%) induced complete cytogenetic response, major cytogenetic response and major molecular response. Conclusion: The population of this study obtained lower-than-expected therapeutic responses compared to other studies. .

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BACKGROUND: In 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. OBJECTIVE: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. METHODS: This 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. RESULTS: The 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. CONCLUSION: Significant 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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Background: In 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. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This 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. Results: The study population consisted of 100 patients who were mostly male (51%) with ages rangingbetween 21 and 40 years (42%), from the countryside (59%), in the chronic phase (95%), with high-riskprognostic factors (40%); the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant 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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The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.

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BACKGROUND: Microcirculation dysfunction, as a consequence of localized vascular insufficiency, is considered to be one of the dominant causes of surgical flap necrosis. Several vasoactive drugs have been tested for the pharmacological treatment of tissue ischemia, with varying degrees of success. This study aimed to assess the impact of buflomedil and sildenafil on the viability of random skin flaps in rats. METHODS: Caudally pedicled skin flaps (10 x 3 cm) were created on the backs of rats. The animals were randomly assigned, in groups of 10, to three treatment groups: one group served as the vehicle control group, one group received buflomedil (10 mg/kg/d, orally), and a third group received the same dosage of sildenafil. Following seven days of dosing, the animals were sacrificed, and the viable flap area was determined. RESULTS: The average viable flap area for each group was: 16.2 ± 3.56 cm² (control group), 17.69 ± 2.54 cm² (buflomedil group), and 18.28 ± 3.74 cm² (sildenafil group). Data analysis by the Kruskal-Wallis test failed to show a statistically significant difference between the three groups. CONCLUSIONS: Neither buflomedil nor sildenafil showed a reduction in the necrotic area of random skin flaps in rats.

INTRODUÇÃO: A insuficiência no aporte sanguíneo e a consequente disfunção gerada no fluxo da microcirculação são consideradas causas dominantes de sofrimento de um retalho cirúrgico. Várias drogas vasoativas têm sido testadas para o tratamento farmacológico da isquemia tecidual, porém com graus variáveis de sucesso. Este estudo teve como objetivo avaliar a influência do buflomedil e do sildenafil na viabilidade de retalhos cutâneos ao acaso, em ratos. MÉTODO: Foram confeccionados retalhos cutâneos no dorso de ratos, com dimensões de 10 x 3 cm e base caudal. Foram utilizados 30 ratos, divididos em três grupos de 10 ratos cada: um grupo que recebeu apenas o veículo da solução (grupo controle); um grupo que recebeu buflomedil (grupo buflomedil); e um terceiro grupo que recebeu sildenafil (grupo sildenafil). A via de administração foi a oral e a dose foi de 10 mg/kg/dia para cada droga, durante sete dias. Ao final desse período, os animais foram sacrificados, sendo realizada a determinação das áreas viáveis dos retalhos. RESULTADOS: A média das áreas viáveis dos retalhos foi de 16,2 ± 3,56 cm² para o grupo controle, de 17,69 ± 2,54 cm² para o grupo buflomedil, e de 18,28 ± 3,74 cm² para o grupo sildenafil. A análise dos dados pelo teste de Kruskal-Wallis não demonstrou significância estatística entre os três grupos. CONCLUSÕES: A utilização do buflomedil e do sildenafil demonstrou não diminuir a área de necrose de retalhos randomizados em ratos.

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Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug.

RESUMO

The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.

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Dasatinib is a highly effective second generation tyrosine kinase inhibitor approved for the treatment of imatinib-resistant or intolerant chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. This article reviews the results of phase I, II and III studies and looks at the efficacy and safety of dasatinib. This review also provides practical recommendations for the management of side effects.

RESUMO

Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug.

Assuntos

RESUMO

Dasatinib is a highly effective second generation tyrosine kinase inhibitor approved for the treatment of imatinib-resistant or intolerant chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. This article reviews the results of phase I, II and III studies and looks at the efficacy and safety of dasatinib. This review also provides practical recommendations for the management of side effects.

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