RESUMEN
Pathological angiogenesis is increasingly recognized to be an important feature of pathogenesis in solid tumors and also in leukemias. Specific blockers of angiogenesis are now being introduced into early clinical trials with encouraging results. Vascular endothelial growth factor (VEGF) seems to play a central role in tumor angiogenesis and is associated with a poor prognosis in both solid tumors and adult leukemias. In pediatric acute lymphocytic leukemia however, the expression of angiogenic molecules and its relation to prognosis and relapse are unknown. Therefore, we prospectively analyzed 46 pediatric patients with precursor B cell acute lymphocytic leukemia by semi-quantitative RT-PCR for expression of the angiogenic molecules VEGF, VEGF-C, iNOS and TGF-beta and correlated relapse and survival data with the expression of these factors. We found a high mRNA expression of TGF-beta and iNOS, a moderate expression of VEGF but no expression of bFGF and VEGF-C. A significantly higher expression of VEGF mRNA was found in patients with late relapses compared to patients without relapses (p=0.043). A significantly higher mRNA expression of iNOS was found in surviving patients compared with non-surviving patients (p=0.023). Angiogenic factors are expressed in the bone marrow of patients with pediatric B cell precursor ALL and VEGF is a potential candidate for therapeutic intervention as it is significantly higher expressed in children with late relapses. The mRNA expression of iNOS in the surviving children possibly reflects an increased activity of the immune system against the leukemia which leads to a superior survival.
Asunto(s)
Proteínas Angiogénicas/biosíntesis , Linfoma de Burkitt/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Proteínas Angiogénicas/genética , Células de la Médula Ósea/metabolismo , Linfoma de Burkitt/genética , Niño , Preescolar , Femenino , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Factor 2 de Crecimiento de Fibroblastos/genética , Humanos , Lactante , Masculino , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genética , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Factor C de Crecimiento Endotelial Vascular/genéticaRESUMEN
Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis.