Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

ABSTRACT Introduction and objective: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. Methods: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. Results: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65 × 103/L, 396 × 103/L, and 327.05 × 103/L, respectively (p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p = 0.226) Conclusion: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

INTRODUCTION AND OBJECTIVE: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. METHODS: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. RESULTS: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65×103/L, 396×103/L, and 327.05×103/L, respectively (p=0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p=0.395 and p=0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p>0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p=0.226) CONCLUSION: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital.

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.

Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital

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. .

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.

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.

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

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. .

Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJECTIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. CONCLUSION: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

Influência do CD 20 na refratariedade do linfoma de Hodgkin clássico ao tratamento inicial com o esquema ABVD, no Ceará, Brasil / Influence of CD 20 antigen expression in the refractoriness of classical Hodgkin lymphoma in the first line treatment with ABVD protocol in Ceará state, Brazil

INTRODUÇÃO: A significância prognóstica do marcador imunológico CD 20 no linfoma de Hodgkin clássico (LHc) ainda é incerta, particularmente no que se refere à refratariedade ao tratamento inicial. OBJETIVOS: Avaliar a influência da positividade do marcador CD 20 na refratariedade do LHc ao tratamento poliquimioterápico inicial, com o esquema doxorubicina 25 mg/m², bleomicina 10 mg/m², vinblastina 6 mg/m² e dacarbazina 375 mg/m² (ABVD), no Ceará, Brasil. MATERIAL E MÉTODOS: Estudo analítico incluindo 97 pacientes com diagnóstico de LHc firmado entre janeiro de 2000 e dezembro de 2004. A análise foi realizada avaliando variáveis demográficas, clínicas e laboratoriais. RESULTADOS: Foi evidenciada uma positividade do CD 20 em 38,1 por cento dos pacientes. Na análise bivariada, CD 20 positivo (razão de chance [RC] = 4,02; intervalo de confiança [IC] = 1,09 - 8,54; p = 0,02), a presença de sintomas B (RC = 4,02; IC = 1,18-17,51; p = 0,01) e a elevação da desidrogenase lática (mediana não-refratários 248,5 [200,5 - 389,5]; mediana refratários 356 [208,5 - 545]; p = 0,03) apresentaram relação de pior prognóstico quanto à refratariedade. Na regressão logística, o CD 20 positivo (RC ajustada = 3,6; IC = 0,99 - 13,09; p = 0,05) e a presença de sintomas B (RC ajustada = 5,41; IC = 1,16 - 25,34; p = 0,03) continuaram apresentando pior prognóstico. DISCUSSÃO: Esses dados coincidem com a literatura, em que a positividade do marcador CD 20 está relacionada com pior resposta ao tratamento com ABVD. CONCLUSÃO: Os nossos dados indicam que o tratamento com ABVD não é completamente adequado para a abordagem terapêutica inicial deste subgrupo de pacientes e novas pesquisas precisam ser realizadas no sentido de aperfeiçoar o tratamento destes pacientes.

INTRODUCTION: The prognostic value of CD20 antigen expression in classical Hodgkin lymphoma (cHL) is uncertain, particularly regarding the refractoriness to first-line treatment. OBJECTIVES: To assess the influence of CD20 positiveness on the refractoriness of cHL to first-line chemotherapy with ABVD protocol in Ceará State, Brazil. MATERIAL AND METHODS: Analytical study including 97 patients diagnosed with cHL between January/2000 and December/2004. The analysis was performed evaluating demographic, clinical and laboratory variables. RESULTS: CD20 antigen expression was positive in 38.1 percent of the patients. In the bivariate analysis, CD20 antigen expression (OR = 4.02; CI = 1.09 - 8.54; p = 0.02), the presence of B-symptoms (OR = 4.02; CI = 1.18-17.51; p = 0.01) and an elevated lactate dehydrogenase level (median not refractory 248.5 [200.5 - 389.5]; median refractory 356 [208.5-545]; p = 0.03) showed worse prognosis as to refractoriness. In the logistic regression analysis, the presence of CD 20 (OR = 3.6; CI = 0.99-13.09; p = 0.05) and B-symptoms (OR = 5.41; CI = 1.16-25.34; p = 0.03) continued to show worse prognosis. DISCUSSION: These findings coincide with literature data indicating that CD 20 antigen expression is associated with low response to treatment with ABVD. CONCLUSION: Our data show that the treatment with ABVD is not totally appropriate for the initial therapeutic approach in this subgroup of patients and that further studies are required to optimize their treatment.