The Plasma Concentrations of the Anorexigenic PYY and Orexigenic Ghrelin Decrease and Increase Respectively during Chemotherapy in Children with Acute Lymphoblastic Leukaemia, as the Leukemic Burden Is Gradually Eliminated and the Body Weight Improves.

Abstract

Anorexia and cachexia are common manifestations in children with acute lymphoblastic leukaemia (ALL) at diagnosis. Possible mediators of the anorexia-cachexia syndrome are hormones, cytokines, and adipokines from peripheral tissues, and neurotransmitters, neuropeptides, cytokines, and other hormones in the hypothalamus. Peptide YY (PYY) and ghrelin are gastrointestinal track-derived hormones involved in the short- and long-term regulation of food intake and energy balance. PYY, synthesized mainly by endocrine cells of the terminal ileum and colon, is released into the systemic circulation in response to a meal and participates in signalling the end of the meal at the hypothalamus. PYY exerts its pro-satiety actions possibly through an Y2 receptor-mediated mechanism. Ghrelin, secreted predominantly from X/A-like endocrine cells of the oxyntic glands of the stomach, is primarily secreted in the fasting state, with plasma concentrations falling within one hour of a meal. Its role in food intake and energy balance is opposite to that of PYY, as it exerts orexigenic effects through activation of the hypothalamic neuropeptide Y-Y1 (NPY-Y1) pathway. We evaluated the secretion of PYY and ghrelin at diagnosis and during chemotherapy in children with ALL. Ten patients aged 2-7years were included in this perspective study. All patients were treated following the same protocol (HOPDA97)1. A physical examination was performed and blood chemistries were evaluated by standard techniques. Preprandial PYY and active ghrelin levels were determined by specific radioimmunoassays (Linco Research, Inc., USA). Measurements were performed at diagnosis prior to chemotherapy and at several time points prior to each next cycle of chemotherapy for up to 18 months (6–10 measurements per patient). Baseline PYY levels were 213.2±85.3pg/ml, increased significantly to 283.9±72.9pg/ml after the induction and consolidation phase of chemotherapy, and returned progressively to pre-treatment levels at the 6th cycle of the maintenance phase. Baseline active ghrelin concentrations at diagnosis were low (32.6±8.6pg/ml), fluctuated throughout the study period and stabilized at significantly higher levels (57.4±31.6pg/ml) after the 8th cycle of maintenance phase of chemotherapy. These data suggest that in children with ALL and anorexia-cachexia the levels of PYY decrease with time, as the leukemic burden is eliminated. In contrast, active ghrelin levels are relatively low at diagnosis, remain low during the early cycles of chemotherapy, but normalize with the elimination of the leukemic burden, paralleling the body weight gain trajectory.