Assuntos
Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Tretinoína/administração & dosagemRESUMO
In a multicenter trial, 259 young adults (15-49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte-macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Leucemia Mieloide/tratamento farmacológico , Pré-Medicação , Doença Aguda , Adolescente , Adulto , Amsacrina/administração & dosagem , Amsacrina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Divisão Celular/efeitos dos fármacos , Terapia Combinada , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide/genética , Leucemia Mieloide/patologia , Leucemia Mieloide/cirurgia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Células-Tronco Neoplásicas/efeitos dos fármacos , Modelos de Riscos Proporcionais , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Risco , Terapia de Salvação , Estimulação Química , Transplante Homólogo , Resultado do TratamentoRESUMO
Post-remission options were compared in a population of 262 relapsing and refractory acute myeloid leukemia patients achieving complete remission (CR) after the same re-induction according to etoposide - mitoxantrone - cytarabine (EMA) trials. The selection of post-remission therapy depended on trial recommendations, age, performance status, and availability of an HLA-identical sibling. One hundred and thirty patients received chemotherapy consolidation courses, 50 received autologous stem cell transplantation (SCT), and 43 underwent allogeneic bone marrow transplantation (BMT), while 39 did not receive any additional therapy. The preliminary analysis identified 3 favorable prognostic factors correlated with event-free survival (EFS): M3 subtype, previous CR duration > 1 year, and transplantation. Three year EFS was 68 vs. 23% with autologous SCT and allogeneic BMT in M3 patients and, respectively, 41 vs. 20% in non-M3 patients. Three year probabilities of treatment-related mortality were 11 and 47%, respectively. A statistical model was conceived with adjustment on prognostic factors and post-remission option. In the multivariate analysis, autologous SCT appeared significantly better than allogeneic BMT (P < 0.01) or chemotherapy (P = 0.001), while allogeneic BMT was not statistically different than chemotherapy. This indicates a high treatment-related toxicity with allogeneic BMT in patients re-induced by highly intensive chemotherapy, and therefore a tendency for a better outcome with autologous SCT as post-remission treatment in those patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Terapia de Salvação , Transplante de Células-Tronco , Doença Aguda , Adolescente , Adulto , Idoso , Terapia Combinada , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Recidiva Local de Neoplasia/mortalidade , Indução de Remissão , Taxa de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Primary resistant acute myeloid leukemia (AML) has a very poor prognosis. Etoposide-mitoxantrone-cytarabine (EMA) timed sequential chemotherapy including a first sequence combining mitoxantrone (12 mg/m(2) per day over 3 days) with cytarabine (500 mg/m(2) per day over the same period), and a second sequence consisting in etoposide (200 mg/m(2) per day for 3 days) and cytarabine as in the first sequence, has been proposed as a salvage regimen. Over a 10-year period, 66 primary resistant AML patients have been treated by EMA salvage chemotherapy. All patients displayed intermediate- or high-risk karyotypic abnormalities. Of the 66 patients, 24 [36%, 95% confidence interval (CI): 25-49%] achieved complete remission (CR). Thirty-eight patients were resistant to EMA chemotherapy and four patients died from toxicity during aplasia. After CR achievement, 18 patients received consolidation therapy. Five patients with an HLA-identical sibling donor underwent allogeneic stem cell transplantation (SCT), one patient received autologous SCT, two patients received a second course of EMA chemotherapy, and ten were scheduled for 6-monthly maintenance courses (mini-EMA). Median follow-up was 7.3 years. At the time of analysis, 21 of the 24 patients (87%) who achieved CR have relapsed. Median disease-free survival (DFS) was 5 months (95% CI: 4.3-7.7 months). Median overall survival (OS) was 5 months (95% CI: 3.8-6.7 months). There were only two long-term remitters (3%). In the univariate analysis, CR achievement was mainly related to white blood cell (WBC) count at the time of starting salvage therapy with poorer outcome for patients with more aggressive leukemia (WBC count > or =10 x 10(9)/l) (CR rates: 50% vs 10%, p<0.001). Overall survival was also influence by WBC count (median OS: 7.2 months vs 2.8 months, respectively, for WBC