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A importância das características clínico-laboratoriais e do halving time na avaliação de resposta molecular na leucemia mielóide crónica: estudo retrospectivo de um grupo de doentes
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Advisor(s)
Abstract(s)
Introdução: Na Leucemia Mielóide Crónica (LMC), a monitorização de
resposta ao tratamento com inibidores de tirosina-cinase (TKI) baseia-se na
avaliação da resposta hematológica, citogenética e molecular ao longo do
tempo, estando definidos critérios de resposta óptima, sub-óptima e falência
aos 3, 6 e 12 meses de tratamento. Os doentes com mais de 10% de
transcrito BCR-ABL1 aos 3 meses são considerados como tendo resposta
sub-óptima e pior prognóstico a longo prazo. No entanto, existe uma
proporção de doentes que atingem respostas moleculares favoráveis
posteriormente.
Objectivos: Num grupo de doentes com LMC, em fase crónica, sob
tratamento com Imatinib (IM), avaliar as diferenças clínico-laboratoriais entre
os doentes com resposta molecular óptima e resposta sub-óptima aos 3
meses de tratamento. Nos doentes com resposta sub-óptima, avaliar a
capacidade do halving time e da redução logarítmica de predizer respostas
moleculares subsequentes.
Material e Métodos: Análise retrospectiva de um grupo de 24 doentes com
LMC, em fase crónica, diagnosticados no nosso centro entre 1 de Janeiro de
2006 e 31 de Agosto de 2014. Revisão dos parâmetros clínico-laboratoriais e
avaliação de resposta óptima, sub-óptima e falência aos 3, 6 e 12 meses de
tratamento. Determinação do halving time e redução logarítmica da %BCRABL1
em doentes com resposta sub-óptima aos 3 meses de Imatinib.
Resultados: Aos 3 meses de tratamento, 14 doentes tinham resposta óptima
e 10 sub-óptima. Os doentes com resposta sub-óptima apresentavam um
valor mais elevado de transcrito ao diagnóstico (p<0,05). Neste grupo de
doentes, o halving time tem valor preditivo de falência de resposta
(AUC=0,83; p=0,02) e de resposta molecular óptima aos 6 meses
(AUC=0,93; p<0,0001). A redução logarítmica aos 3 meses foi preditiva de
resposta molecular óptima aos 6 meses (AUC=0,96; p<0,0001) e aos 12
meses (AUC=0,83; p=0,03). Um valor de 22,59 dias de halving time e uma
redução logarítmica de -1,1log aos 3 meses de tratamento, parecem ter um
bom poder discriminativo dos doentes que alcançam resposta molecular
óptima aos 6 meses.
Conclusão: Estes resultados sublinham a importância da quantificação de
transcrito ao diagnóstico na interpretação da resposta molecular obtida aos 3
meses, assim como o contributo, numa fase precoce de tratamento, de
parâmetros de cinética de decréscimo de transcrito na discriminação dos
doentes com resposta sub-óptima aos 3 meses que alcançarão
posteriormente respostas moleculares favoráveis.
Introduction: In Chronic Myeloid Leukaemia (CML), the response to treatment with tyrosine-kinase inhibitors is monitored based on the evaluation of hematologic, cytogenetic and molecular responses, with specific criteria defining responses as optimal, suboptimal or failure at 3, 6 and 12 months of treatment. Patients with BCR-ABL1 transcript above 10% at 3 months are considered suboptimal responders, with worse long-term outcomes. However, a proportion of these patients will still achieve a favourable molecular response. Aims: To evaluate the clinic and laboratory differences between patients with optimal and suboptimal response at 3 months, in a group of patients with chronic-phase CML treated with Imatinib. Within suboptimal responders, to evaluate the predicting value of subsequent molecular response of the halving time and logarithmic reduction. Methods: Retrospective analysis of a group of 24 patients with chronic-phase CML, diagnosed in a single centre between January 2006 and August 2014. Review of the clinic and laboratory parameters and response evaluation at 3, 6 and 12 months of treatment. Determining the halving time and logarithmic reduction of %BCR-ABL1 in the group of patients with suboptimal response at 3 months of treatment with Imatinib. Results: After 3 months of treatment, 14 and 10 patients had optimal and suboptimal responses, respectively. Patients with suboptimal response presented with a higher transcript value at diagnosis (p<0,05). In this group of patients, the halving time was predictive of response failure (AUC=0,83; p=0,02) and optimal response at 6 months (AUC=0,93; p<0,0001). The logarithmic reduction at 3 months was predictive of optimal molecular response at 6 (AUC=0,96; p<0,0001) and 12 months (AUC=0,83; p=0,03). An halving time of 22,59 days and a -1,1log reduction at 3 months of treatment showed a good predictive value of achieving an optimal response at 6 months. Conclusion: These results outline the importance of transcript quantification at the time of diagnosis in the interpretation of the 3-month molecular response, as well as the role of kinetic parameters of transcript decrease, at an early timepoint, in discriminating patients with suboptimal response at 3 months that will respond favorably in the long-term.
Introduction: In Chronic Myeloid Leukaemia (CML), the response to treatment with tyrosine-kinase inhibitors is monitored based on the evaluation of hematologic, cytogenetic and molecular responses, with specific criteria defining responses as optimal, suboptimal or failure at 3, 6 and 12 months of treatment. Patients with BCR-ABL1 transcript above 10% at 3 months are considered suboptimal responders, with worse long-term outcomes. However, a proportion of these patients will still achieve a favourable molecular response. Aims: To evaluate the clinic and laboratory differences between patients with optimal and suboptimal response at 3 months, in a group of patients with chronic-phase CML treated with Imatinib. Within suboptimal responders, to evaluate the predicting value of subsequent molecular response of the halving time and logarithmic reduction. Methods: Retrospective analysis of a group of 24 patients with chronic-phase CML, diagnosed in a single centre between January 2006 and August 2014. Review of the clinic and laboratory parameters and response evaluation at 3, 6 and 12 months of treatment. Determining the halving time and logarithmic reduction of %BCR-ABL1 in the group of patients with suboptimal response at 3 months of treatment with Imatinib. Results: After 3 months of treatment, 14 and 10 patients had optimal and suboptimal responses, respectively. Patients with suboptimal response presented with a higher transcript value at diagnosis (p<0,05). In this group of patients, the halving time was predictive of response failure (AUC=0,83; p=0,02) and optimal response at 6 months (AUC=0,93; p<0,0001). The logarithmic reduction at 3 months was predictive of optimal molecular response at 6 (AUC=0,96; p<0,0001) and 12 months (AUC=0,83; p=0,03). An halving time of 22,59 days and a -1,1log reduction at 3 months of treatment showed a good predictive value of achieving an optimal response at 6 months. Conclusion: These results outline the importance of transcript quantification at the time of diagnosis in the interpretation of the 3-month molecular response, as well as the role of kinetic parameters of transcript decrease, at an early timepoint, in discriminating patients with suboptimal response at 3 months that will respond favorably in the long-term.
Description
Keywords
Leucemia Mielóide Crónica BCR-ABL1>10% Resposta sub-óptima Halving time Redução logarítmica