Plasma amino acid concentrations in patients with acute myelogenous leukemia.

Changes in plasma-free amino acid (PFAA) concentrations in the presence of solid tumors have been widely described. Conversely, the PFAA profile in patients with acute leukemias is less well defined. The aim of the present study was to clarify whether the PFAA profile is altered in patients with acute myeloid leukemia (AML), whether the profile differs from the PFAA profile of solid tumors, and whether it may predict outcome of AML. Fasting PFAA were measured in 40 untreated, normally nourished patients with AML (17 males, 23 females), ages 22-78 y, with white blood cell (WBC) counts ranging from 1.08 to 276.5 x 10(3)/cm2, and in 24 healthy volunteers. Plasma concentrations (mu mol/L, mean +/- SE) of glutamic acid (GLU), free tryptophan (FTRP), ornithine (ORN), and glycine (GLY) were significantly higher in AML (GLU: 90.2 +/- 6.1 versus 37 +/- 8; FTRP: 7.0 +/- 0.6 versus 4.8 +/- 0.3, P < 0.005; ORN: 108.7 +/- 5.8 versus 78 +/- 6, P < 0.001; GLY: 295.0 +/- 14.8 versus 239 +/- 9, P < 0.01), whereas serine (SER), methionine (MET), and taurine (TAU) were significantly lower in AML than in controls (SER: 109.0 +/- 5.8 versus 130 +/- 4, P < 0.03; MET: 25.5 +/- 1.3 versus 33 +/- 3, P < 0.03; TAU: 46.5 +/- 3.5 versus 81 +/- 2, P < 0.001), and tended to be even lower in patients who had not responded to chemotherapy or had relapsed within 18 mo of enrollment. Such changes were unrelated to age, sex, and WBC count. Changes in PFAA that occur in AML are only in part similar to those observed in solid tumors. The reduction of TAU appears to be a typical feature of AML and might be secondary to the deficiency of its precursors SER and MET. Further studies are under way aimed at clarifying whether PFAA might predict prognosis in AML, whether PFAA is normalized by remission induction, and if its correction may be of any benefit for patients with hematologic malignancies.

Clinical and metabolic effects of different parenteral nutrition regimens in patients undergoing allogeneic bone marrow transplantation.

BACKGROUND: Nutrients may interfere with physiological and pathophysiologic mechanisms. The present study was aimed at evaluating whether the differences in the quality of energy substrates administered with total parenteral nutrition (TPN) after cytoreductive therapy may influence the clinical outcome of patients undergoing bone marrow transplantation (BMT). METHODS: Sixty-six consecutive allogeneic BMT patients with hematologic malignancies were randomized to receive either a glucose-based (100% glucose) or a lipid-based (80% lipid, using an omega-6 long-chain triacylglycerol emulsion + 20% glucose) TPN, providing 146.3 kJ/kg body weight, 1.4 g of protein/kg of body weight, administered from day +1 to day +15 after BMT. Time to engraftment (EGT), incidence of sepsis and metabolic complications (hyperglycemia and hypertriglyceridemia), incidence of acute graft-versus-host-disease (A-GVHD) and relapse, survival at 18 months, incidence of deaths for A-GVHD and relapse were evaluated. RESULTS: Six patients dropped out before completing the study period. Thirty-one patients in the glucose-based TPN group and 29 patients in the lipid-based TPN group were evaluated. The incidence of hyperglycemia was significantly lower in the lipid-based TPN group than in the glucose-based TPN group (3.4% vs. 32%, respectively; P=0.004). Five patients in the glucose group and none in the lipid group died for A-GVHD (P<0.05). Survival at 18 months tended to be higher in the lipid group than in the glucose group (62% vs. 42%, P=NS). Rate of bone-marrow EGT, time to EGT, incidence of sepsis and fungal infections during TPN, incidence of A-GVHD, and rate of relapse at 18 months were not different in the two groups. CONCLUSIONS: The results obtained suggest that the use of lipid-based TPN after allogeneic BMT is associated with lower incidence of lethal A-GVHD and hyperglycemia, without negatively affecting the EGT of infused cells. Intravenously administered lipids might have influenced the severity of A-GVHD likely via modulation of immune response and synthesis of cytokines, prostaglandins, and leukotrienes that participate in the pathogenesis of graft-versus-host disease.

Plasma tryptophan levels and anorexia in liver cirrhosis.

OBJECTIVE: Increased brain tryptophan (TRP) availability for serotonin synthesis may play a role in the pathogenesis of anorexia. Since in chronic liver failure, increased plasma and cerebrospinal fluid TRP concentrations are characteristically reported, we hypothesize that also in liver cirrhosis increased brain TRP availability may constitute the pathogenic mechanism of anorexia. To test this hypothesis, the association between anorexia and plasma TRP was investigated. METHODS: Anorexia and plasma amino acid concentrations were evaluated in 16 patients with liver cirrhosis and compared with those obtained in 13 healthy volunteers. RESULTS: According to a questionnaire, 11 cirrhotic patients were considered as anorectic. In these patients, brain TRP availability was significantly higher than in nonanorectic patients and controls. DISCUSSION: Increased brain TRP availability is also associated with anorexia in liver cirrhosis, and supports the hypothesis that increased serotonergic activity may constitute the common pathogenic mechanism for anorexia associated with different diseases.

Biochemical indices may not accurately reflect changes in nutritional status after allogeneic bone marrow transplantation.

The validity of biochemical indices routinely used for nutritional assessment was evaluated in patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Sixteen patients received total parenteral nutrition (TPN) for 15 days (35 kcal kg.body wt-1.day-1; 1.4 g amino acid.kg body wt-1.day-1) starting 1 day after transplantation. Nutritional status was evaluated before and after the TPN period by determining anthropometric (body weight, triceps skinfold thickness, and midarm circumference) and biochemical (transferrin, prealbumin, ceruloplasmin, and C3c) indices. Anthropometric indices, which were within the normal range before TPN, were not changed on day 15; transferrin and prealbumin concentrations significantly (p = 0.03) decreased whereas ceruloplasmin and C3c significantly (p = 0.03) increased. The levels of acute-phase proteins (alpha-1-acid glycoprotein, alpha-1-antitrypsin, and C-reactive protein), determined in 8 of the 16 patients at the same time intervals, were increased after 15 days of TPN and were significantly inversely correlated with transferrin and prealbumin. On the basis of these data, it appears that biochemical indices are not sufficiently reliable in the nutritional assessment of bone marrow transplantation patients because the levels of these substances are markedly affected by the acute-phase response secondary to febrile episodes and graft-versus-host disease, which frequently complicate transplantation.

Tumor-induced changes in host metabolism: a possible marker of neoplastic disease.

A large number of "biologic markers" for cancer have been described, including tumor-associated antigens, ectopic hormones, enzymes, and effects of tumor on the host's metabolism. Although tumors may metabolically differ from each other, they may induce similar derangements in glucose, lipid, and protein metabolism in the host. In particular, changes in carbohydrate metabolism may induce glucose intolerance that may be early and easily detected using an oral glucose tolerance test. Hypertriglyceridemia and reduced exogenous lipid clearance may represent an early marker of deranged lipid metabolism. Changes in protein metabolism, as reflected by plasma amino acid profile, may also represent a new diagnostic tool for cancer. Among other amino acids, free tryptophan seems to be the best candidate as a new useful marker for monitoring neoplastic disease. It is conceivable that, based on the understanding of the differences in plasma amino acid profiles, more specific and rational antineoplastic strategies may arise.

Plasma amino acid imbalance in patients with lung and breast cancer.

In order to evaluate whether different solid tumors may specifically influence plasma free amino acid (PFAA) profile, PFAA were analysed in seventy-four patients with lung (41 patients) and breast cancer (33 patients) and 28 healthy subjects. In lung cancer patients a significant reduction of gluconeogenic amino acids, threonine, serine, glycine and a significant increase of free tryptophan and glutamic acid was found. In breast cancer patients a significant increase of ornithine, glutamic acid and free tryptophan was found. The comparison of PFAA profiles between lung and breast cancer suggests that different tumors have a different influence on the host's PFAA pattern.

Cytokines, tryptophan and anorexia in cancer patients before and after surgical tumor ablation.

Serotoninergic system activity and cytokine production have been both implicated in the pathogenesis of cancer anorexia. To verify the existence of relationships between tryptophan, cytokines and anorexia, twenty cancer and six non-neoplastic patients were studied. Plasma amino acid concentration, including tryptophan, and spontaneous and LPS stimulated tumor necrosis factor and interleukin-1 release from peripheral blood mononuclear cells were determined before and after surgery in both groups of patients. A close relationship between plasma free tryptophan concentration and anorexia was observed, whereas no relationship between cytokine production and either anorexia or plasma tryptophan was found in cancer patients.