RESUMEN
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.
Asunto(s)
Mesilato de Imatinib/uso terapéutico , Células Asesinas Naturales/citología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Estudios de Casos y Controles , Citocinas/metabolismo , Dasatinib/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Recuento de Linfocitos , Subgrupos Linfocitarios/citología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Privación de TratamientoRESUMEN
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
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Tioguanina/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Anemia Refractaria con Exceso de Blastos/tratamiento farmacológico , Anemia Refractaria con Exceso de Blastos/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Transformación Celular Neoplásica , Citarabina/efectos adversos , Daunorrubicina/efectos adversos , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Leucemia Mieloide/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/patología , Estudios Prospectivos , Inducción de Remisión , Tasa de Supervivencia , Tioguanina/efectos adversosRESUMEN
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.