RESUMO
The initial chemotherapy in acute myeloid leukaemia (AML) comprises a first phase of induction and a second phase of consolidation. In the majority of patients, the induction treatment leads to complete remission (CR), defined as microscopic disappearance of leukaemic disease along with the return of normal haematopoiesis. However, despite the introduction of more efficacious consolidation regimens, a worryingly large proportion of AML patients in CR will subsequently experience relapses with poor prospects of long-term survival. A relapse is assumed to be the result of expansion of residual leukaemic cells that have escaped the initial chemotherapy. The anti-leukaemic functions of T cells and natural killer (NK) cells has formed the background to the use of interleukin-2 (IL-2), a T- and NK cell-activating cytokine, with the aim to eliminate residual leukaemia and hence reduce the relapse rate in AML, but the clinical trials using IL-2 monotherapy have yielded disappointment. A recent phase III study has demonstrated that post-consolidation treatment with the combination of histamine dihydrochloride (HDC) and IL-2 significantly prevents relapse in AML patients. Here we account for the preclinical background to the use of HDC/IL-2 in AML along with a review of clinical results.
Assuntos
Antineoplásicos/uso terapêutico , Agonistas dos Receptores Histamínicos/uso terapêutico , Histamina/uso terapêutico , Imunoterapia/métodos , Interleucina-2/uso terapêutico , Leucemia Mieloide Aguda/terapia , Animais , Ensaios Clínicos como Assunto , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Agonistas dos Receptores Histamínicos/uso terapêutico , Histamina/uso terapêutico , Interleucina-2/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Quimioterapia Combinada , Histamina/imunologia , Agonistas dos Receptores Histamínicos/imunologia , Humanos , Interleucina-2/imunologia , Leucemia Mieloide Aguda/imunologia , Indução de RemissãoRESUMO
Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection, especially in patients infected with genotype 3 virus, but its significance for the outcome of antiviral treatment is not fully understood. We have monitored steatosis in liver biopsies from 231 patients with chronic HCV infection who received pegylated recombinant interferon-alpha and ribavirin in a phase III study (DITTO trial). The degree of steatosis, along with relevant metabolic parameters, was correlated with the early disappearance of virus and with the final outcome of treatment. Our data suggest that the presence of steatosis impairs the early reduction of viral load during treatment in patients infected with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Based on these findings, we propose that interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of benefit to patients infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on the other hand, should be offered early antiviral treatment.