RESUMO
Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.
Assuntos
Mesilato de Imatinib/uso terapêutico , Células Matadoras Naturais/citologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Estudos de Casos e Controles , Citocinas/metabolismo , Dasatinibe/uso terapêutico , Intervalo Livre de Doença , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Contagem de Linfócitos , Subpopulações de Linfócitos/citologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Suspensão de TratamentoRESUMO
In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Tioguanina/uso terapêutico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transformação Celular Neoplásica , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Tioguanina/efeitos adversosRESUMO
Three patients (aged 68-75 years) with histologically confirmed relapsed or refractory high-grade non-Hodgkin's lymphoma were entered in this pilot study in which gemcitabine 800 mg/m2 was given as a 30 min i.v. infusion once a week for 3 weeks. One patient responded with complete remission and the other two with partial remission and stable disease for 2 and 3 months, respectively. Haematological toxicity was modest with grade 4 leucopenia (one cycle) and grade 4 thrombocytopenia (two cycles). The activity and mild toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of high-grade non-Hodgkin's lymphoma.