RESUMO
PURPOSE: The aim of the present study was to investigate the efficacy and adverse effects of HCAG and FLAG re-induction chemotherapy in acute myeloid leukemia (AML) patients of low- and intermediate-risk groups following induction failure. METHODS: A total of 98 AML patients were enrolled. Among these subjects, 47 patients were treated with HCAG chemotherapy, while 51 patients were treated with FLAG chemotherapy. RESULT: The complete remission (CR) and overall remission (OFF) were 24% and 38%, respectively in patients with HCAG induction chemotherapy, while the corresponding percentages were 28% and 42% in subject receiving FLAG chemotherapy. The median survival time of progress-free survival (PFS) was 29.8 (95% CI 23.749-35.851) months in the HCAG group and 30.8 (95% CI 21.728-39.872) months in the FLAG group (P = 0.620). A total of 42 patients in the HCAG group suffered from grade 4 hematological toxicity, while this adverse reaction was noted for all patients who were treated with FLAG chemotherapy (P = 0.023). A total of 19 cases indicated apparent nonhematological toxicity in the HCAG group, while only 40 (78.4%) were noted with these adverse reactions in the FLAG group (P = 0.000). CONCLUSION: The HCAG regimen exhibited a similar effect compared with the FLAG regimen in low- and intermediate-risk groups, although the HCAG regimen significantly decreased the toxicity compared with that noted in the FLAG regimen group.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Aclarubicina/administração & dosagem , Aclarubicina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mepesuccinato de Omacetaxina/administração & dosagem , Mepesuccinato de Omacetaxina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Risco , Método Simples-Cego , Falha de Tratamento , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivadosRESUMO
The K562 cell line has erythroid origin and is used for the study of fetal haemoglobin (HbF) production after treatment with several drugs, such as hydroxyurea, cisplatin and cytosine arabinoside (Ara C). It represents an important tool for the study of cancer differentiation therapy and treatment of thalassaemia and sickle cell disease. Although subject to intense research, the mechanisms involved in the induction of HbF are not fully established, and the regulation of several genes and signalling pathways has been proposed. Using the methodology of differential display, we investigated the changes in gene expression in K562 cells treated with doxorubicin and aclarubicin, which induce HbF expression and cell cycle arrest. Several genes were shown to present differential expression patterns, many of them related to the iron signalling pathway. Particular attention was given to Ndrg1, expressed as early as 24 h after treatment, which can be regulated by iron and is involved with blocking of the cell cycle. A review of the literature shows that, similar to doxorubicin and aclarubicin, most of the drugs used to induce HbF present some kind of effect on the iron signalling pathway, activating in the cells the machinery necessary for the incorporation of extracellular iron. Considering these results, as well as the fact that in erythroid cells the synthesis of haemoglobin is of vital importance, we propose that the production of fetal haemoglobin in erythroid cells is highly dependent on the iron signalling pathway.