Clinical and metabolic effects of different parenteral nutrition regimens in patients undergoing allogeneic bone marrow transplantation. Oral eicosapentaenoic acid for complications of bone marrow transplantation. Total parenteral nutrition vs oral diet in autologous hematopoietic cell transplant recipients. [Prospective comparative study of different amino acid and lipid solutions in parenteral nutrition of patients undergoing bone marrow transplantation]. Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Continuous versus cyclic parenteral nutrition during bone marrow transplantation: assessment and follow-up. Hyperalimentation in autologous bone marrow transplantation for solid tumors. Comparison of total parenteral versus partial parenteral plus enteral nutrition. A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study) Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. Parenteral glutamine protects hepatic function during bone marrow transplantation. A pilot study of oral glutamine supplementation in patients receiving bone marrow transplants. Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood. Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation. Effect of oral glutamine supplementation during bone marrow transplantation. A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress. Intravenous branched chain amino acid trial in marrow transplant recipients. Parenteral nutrition in bone marrow transplantation.
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).
                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.
                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.
                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. The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome. Autologous HCT patients often have poor oral intake for 2-4 weeks post transplant. To compare outcomes between patients provided prophylactic total parenteral nutrition (TPN) or an oral diet (OD), 55 well nourished breast cancer/ hematopoietic cell transplantation (HCT) patients were randomized to TPN (n=27), beginning day -1, or OD (n=28). Parameters studied include length of stay (LOS), engraftment, infections, survival, weight, anthropometrics, handgrip strength, and quality of life (QOL) In all, 50% of OD patients were given TPN due to poor oral intake for 10 consecutive days. No significant differences were found between the groups for any of the above parameters except weight and anthropometrics, which were better maintained in the TPN group than the OD group. Trends were seen for increased infections, more stable handgrip strength, and improved QOL in the TPN group vs the OD group. Prophylactic TPN did result in a more intact nutritional status and preservation of lean body mass post transplant but did not impact LOS or survival when compared to OD. For this reason, TPN should be reserved for autologous HCT patients with pretransplant nutritional depletion, complications post transplant, or prolonged poor oral intake. These results should not be extrapolated to allogeneic HCT patients but are likely applicable to other well nourished autologous HCT patients. The patient who will undergo a bone marrow transplant (BMT) has a high protein catabolism in the time period after the infusion of the marrow, and therefore there is a need for an adequate nutritional support. The objective of our study is to analyze the behavior of nutritional assessment parameters, the lipid metabolism, the number of days of mucositis, the number of infections, the number of days to recovery, and the number of hospitalization days when using different parenteral nutrition solutions: 22.5% and 45% branched chain amino acid solutions, and lipid solutions with long chain triglycerides (LCT), vs. medium chain triglycerides (MCT).
                We have carried out a prospective, randomized study in patients who underwent a BMT who received parenteral nutrition. The supply of nitrogen was 1.5 +/- 0.3 g of AA/kg/day (either in standard solution or in a 45% branched chain AA solution). The caloric supply was similar in all the groups, with a proportion of 60% coming from carbohydrates and 40% from lipids, either LCT or MCT/LCT. The nutritional assessment parameters were studied, as well as of the lipid metabolism, and also clinical evolutive data: number of days of mucositis, number of days of PN, number of days hospitalized, number of infections, rate of infection density. All the data were measured and/or quantified 4 times: pretransplant, on day--of the transplant, and after 7 and 14 days after the transplant.
                62 patients were studied. Group A: 19 patients treated with 22.5% branched chain amino acids + 20% LCT. Group B: 26 patients (45% branched chain amino acids + 20% LCT). Group C: 17 patients, (45% branched chain amino acids + 20% MCT/LCT). There is a quicker recover of the marrow in groups B + C: 14.4 vs. 11.7 and 11.1, with a p < 0.05. The nitrogen balance improves significantly in groups B and C (p < 0.05). The retinol-binding protein increases significantly from day 0 to day 7 (p < 0.01) in the LCT group (Group B). The phospholipids decrease in group B after one day (p < 0.05), and after the 7th day (p < 0.05). The triglycerides increase in group C between 7 and 14 days. The LDL/HDL quotient increases in group B after 14 days (p < 0.05). The triglycerides increase in group C between 7 and 14 days. The LDL/HDL quotient will increase in the B group after 14 days (p < 0.05). There are no differences in the number of days of mucositis, the total number of infections, the number of infections per 100 days of hospitalization, or in the number of hospitalization days.
                In patients who are given parenteral nutrition in the period immediately after the BMT, we found an improvement in the catabolic metabolism parameters when using a solution with a high proportion of branched chain amino acids (45%) and a smaller alteration of the metabolism of the plasmatic lipoproteins when we use MCT/LCT enriched solutions. Glutamine (Gln) is an important nutrient substrate for lymphocytes and macrophages in vitro. This pilot study evaluated effects of Gln supplementation on circulating lymphocytes and lymphocyte subsets after allogeneic bone marrow transplantation (BMT). Adult patients received either parenteral nutrition supplemented by L-Gln (Gln-PN) or standard Gln-free PN after BMT. Leukocyte and total lymphocyte counts were determined during hospitalization, and flow cytometry studies of peripheral mononuclear cells were performed 1 to 2 weeks after hospital discharge. The Gln-PN group demonstrated a higher percentage of blood lymphocytes during hospitalization. At flow cytometry, patients who received Gln-PN had an increased total lymphocyte count (332 +/- 50 versus 590 +/- 71 cells/microL, P = 0.010); greater numbers of total T lymphocytes (54 +/- 19 versus 229 +/- 70 cells/microL, P = 0.030); and higher CD4+ and CD8+ T-lymphocyte counts in peripheral blood compared with controls. Gln-PN may support lymphocyte recovery after BMT. Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition. Outpatient parenteral nutrition (PN) is often given to marrow transplant recipients after high-dose chemoradiotherapy until the resumption of adequate oral intake; however, it may adversely prolong resumption or oral calorie intake by contributing to early satiety.
                A double-blind, randomized study compared standard PN (final concentration 25% dextrose, 5% amino acids) with a hydration solution (5% dextrose) during the first 28 days of outpatient treatment. Patients were eligible for the study if they were > or = 2 years of age, < 65 days posttransplant, had < 70% oral caloric intake at hospital discharge, and required < or = 10 U insulin/L PN. Solutions were provided until the patient's oral intake met > or = 85% caloric requirements for 3 consecutive days.
                Two hundred fifty-eight marrow transplant recipients (128, PN and 130, hydration solution) were studied. Age, donor type, and diagnoses were similar in the two groups. Time to resumption of > or = 85% oral caloric intake was 6 days sooner in the hydration group than in the PN group (median 10 vs 16 days, respectively; p = .049). When adjusting for sex, age, donor type, total body irradiation, previous oral intake, acute graft-versus-host disease, and prednisone therapy, the hydration group resumed oral intake sooner than the PN group (relative risk = 1.51; 95% confidence interval [CI] 1.04 to 2.19; p = .029). The percentage of weight change from pretransplant values, adjusted for the above covariates and the number of weeks of treatment, indicated that the hydration solution group lost weight (4.63%) compared with the PN group (1.27%) after 4 weeks of therapy (p = .004). Rates of hospital readmissions, relapse of malignancy, and survival did not differ between the two treatment groups.
                We conclude that outpatient PN delays resumption of oral intake and that its replacement with hydration solution does not result in adverse patient outcome. To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation.
                Double-blind, randomized, controlled clinical trial.
                University teaching hospital.
                Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies.
                Parenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula.
                Nitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients.
                The glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (-1.4 +/- 0.5 g/d compared with -4.2 +/- 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 +/- 1 d compared with 36 +/- 2 d; P = 0.017).
                Patients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment. The aim of this prospective, randomized clinical trial was to compare the efficacy of parenteral nutrition (PN) in adult bone marrow transplant (BMT) patients on a continuous (CON) versus a cyclic (CYC) regimen. Twelve patients received CON PN and 12 CYC PN. The groups were homogeneous. CON PN received 27.2 +/- 3.7 kcal/kg/day and for CYC PN 25.9 +/- 4.2 kcal/kg/day (P= 0.45). The duration of PN was 20.4 +/- 7.9 days and 27.3 +/- 13.4 days respectively (P = 0.14). There were no differences between initial and final body weights, either within or between groups. The initial pre-albumin levels were 16.1 +/- 7.5 mg/dl and 20.1 +/- 4.9 mg/dl in CON PN and CYC PN, respectively (P= 0.22), and these were maintained throughout the study. Blood glucose levels did not differ between groups. Measures of liver function were moderately increased, but with no significant differences between groups. There were no significant differences regarding the efficacy of PN or the appearance of complications between CON PN and CYC PN in patients with BMT. Recipients of autologous bone marrow transplantation (ABMT) for solid tumors need nutritional support to maintain their body weight (BW). Severe BW-reduction (9.9%) was noticed retrospectively in ten ABMT patients fed orally, despite intensive counseling or occasional tube feeding. A prospective, randomized study of hyperalimentation (25 g nitrogen (N) and 3400 nonprotein kilocalories) with total parenteral nutrition (TPN) or partial parenteral plus enteral nutrition by tube feeding (PPN/EN) was done in 22 patients. Nutritional assessment included balance measurements of N, Na, K, Cl, P, Ca, Mg, Cu, and Zn, and serial measurements of BW, serum albumin, prealbumin, and transferrin. Both regimens were effective in maintaining BW (maximum percent of change, 2.5) and N-balance. Blood products accounted for an additional N-intake of 13% in both groups. The TPN group had a higher dietary N-intake versus PPN/EN, a positive K balance but negative Ca, Mg, Cu, and Zn balances. More mineral supplementation was given in the PPN/EN group where positive K, Mg, and Zn balances were seen. Visceral proteins and IgG, IgA, and IgM levels were decreased on days 7, 14, and 21. Creatinine clearance increased significantly in both groups. Compared with TPN, the PPN/EN group showed a twofold number of patients with a positive blood culture, although this observation did not reach statistical significance and patients had fewer days of diarrhea (31.1% versus 54.3%, P less than 0.01). Hyperalimentation with PPN/EN is an acceptable alternative to TPN in the nutritional support of ABMT recipients. Severe mucositis is a common cause of morbidity in hematopoietic stem cell transplant (HSCT) recipients. Glutamine has been shown to reduce mucositis in children receiving chemotherapy. Patients were randomized in a double-blind manner to receive glutamine or glycine at a dose of 2 g/m(2)/dose (maximum dose 4 g) twice daily until 28 days post transplant or discharge if sooner. Mucositis was graded by use of a modified Walsh scale. A total of 120 children were evaluable: 57 children received glutamine and 63 received glycine. The mean mucositis score was 3.0+/-0.3 vs 3.9+/-0.4 (P=0.07) in the glutamine and glycine groups, respectively. The glutamine group demonstrated a reduction in mean number of days of intravenous narcotics use (12.1+/-1.5 vs 19.3+/-2.8 in the glycine group, P=0.03) and total parenteral nutrition (17.3+/-1.7 vs 27.3+/-3.6 in glycine group, P=0.01). There was no statistically significant difference in toxicity between the two groups. Glutamine appears to be safe and beneficial in reducing the severity of mucositis. Strong consideration should be given to include oral glutamine supplementation as a routine part of supportive care of SCT patients. Painful oral mucositis is a common complication after bone marrow transplantation (BMT). Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium. This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT. Glutamine or a placebo (glycine) were administered from admission until day +28 in 193 BMT patients in a randomized, double-blind, placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day. In autologous BMT patients (n = 87) glutamine was associated with significantly less mouth pain by self report and by opiate use (5.0+/-6.2 days of morphine for glutamine vs 10.3+/-9.8 days for placebo; P= 0.005). Matched sibling BMT patients had no effect by self report and an increased duration of opiate use (23.2+/-5.7 days for glutamine vs 16.3+/-8.3 days for placebo) (P = 0.002). However, day 28 survival of allogeneic patients was improved by glutamine. No significant differences in TPN use, rate of relapse or progression of malignancy, parenteral antibiotic use, acute or chronic GVHD, or days of hospitalization were observed in either autologous or allogeneic recipients. No toxicity of glutamine was observed. We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients, possibly due to interaction with methotrexate. In a paper by Ziegler et al (Ann Intern Med 116: 821-828, 1992), total parenteral nutrition supplemented with L-glutamine (TPN/GLN) was reported beneficial in patients receiving bone marrow transplantation (BMT) for hematologic malignancies. By using a similar protocol, we studied 29 patients with both hematologic malignancies and solid tumors, and with both allogeneic and autologous BMTs. In a double-blind, randomized approach, patients were given isocaloric, isonitrogenous TPN after BMT until they consumed 50% of their required diet orally. Total body water and extracellular water were measured before and after TPN in 10 patients. Total body water increased in patients receiving standard TPN and decreased significantly in patients receiving TPN/GLN. Length of hospital stay after BMT was significantly (5.8 days) less in patients receiving TPN/GLN. Incidence of positive bacterial cultures, clinical infections, and mortality did not differ significantly between the two groups. When the groups were subdivided into patients with hematologic malignancies and those with solid tumors, there were no significant differences in the above variables associated with TPN/GLN. In 17 of 30 additional hospitalized patients receiving standard TPN, substitution of TPN/GLN did not have discernible clinical or laboratory effects but appeared to be safe. Inclusion of patients with solid tumors and a higher mortality in our patients may have obscured beneficial effects of TPN/GLN observed by others. Although standard supportive care for bone marrow transplant (BMT) recipients includes total parenteral nutrition (TPN), it has not been shown that this is the most appropriate method of nutritional support. To determine whether current BMT recipients require TPN during the early recovery period, we conducted a prospective, randomized clinical trial comparing TPN and an individualized enteral feeding program (counseling, high protein snacks and/or tube feeding). Nutritional assessment included measurement of serum proteins, anthropometry, and body composition analysis. For the latter, total body water and extracellular fluid were measured by standard radioisotope dilution techniques and used to quantitate body cell mass and body fat plus extracellular solids (FAT + ECS). In 27 TPN patients, body composition 28 days after BMT, expressed as a percentage of baseline, was body cell mass, 100%, extracellular fluid, 108%, FAT + ECS, 108%, and in 30 enteral feeding program patients, was body cell mass, 93%, extracellular fluid, 104%, and FAT + ECS, 94%. Only the difference in FAT + ECS was statistically significant (p less than 0.01). Compared to the enteral feeding program, TPN was associated with more days of diuretic use, more frequent hyperglycemia, and more frequent catheter removal (prompted by catheter-related complications), but less frequent hypomagnesemia. There were no significant differences in the rate of hematopoietic recovery, length of hospitalization, or survival, but nutrition-related costs were 2.3 times greater in the TPN group. We conclude that TPN is not clearly superior to individualized enteral feeding and recommend that TPN be reserved for BMT patients who demonstrate intolerance to enteral feeding. We conducted a controlled, double-blind study of parenteral glutamine supplementation in an unselected group of consecutive autologous transplant patients. Patients received 30 g of alanyl-glutamine dipeptide (Dipeptiven; Fresenius-Kabi, Bad Homburg, Germany) or glutamine-free amino acid solution i.v. from day +1 to day +14 or to discharge. All patients were assessed for clinical status, mucositis, blood counts, oral intake and immune reconstitution. Parenteral nutrition was administered according to predefined guidelines. Forty patients were randomized; 21 into the glutamine and 19 into the placebo arm. Glutamine patients had less days with diarrhoea (3.3 +/- 4.0 vs 4.3 +/- 3.0, P = 0.03), but they had more severe oral mucositis (mean 4 +/- 4.7 vs 1.4 +/- 2.3 days of mucositis score >13, P = 0.04), spent more days on opioids (mean 3.5 +/- 4.2 vs 1.2 +/- 2.2 days, P = 0.03) and left hospital later than placebo patients (mean 13.5 +/- 3.1 vs 11.7 +/- 2.4 days after transplant, P = 0.06). There were more relapses (P = 0.02) and deaths (P = 0.05) in the glutamine group. The cost of supportive care (mean 2960 +/- 1694 vs 1534 +/- 513 Euro, P = 0.002) was also greater for glutamine patients, mainly due to the cost of glutamine dipeptide itself. The described mode and dosage of glutamine administration did not produce meaningful benefit in our autologous transplant patients and it was certainly not cost-effective. Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT.
                For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double-blinded, to either oral GLN (n = 35) or glycine-control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high-dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO.
                There were 14 in-hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p > .05). Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN.
                Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long-term effects of GLN in BMT seems warranted. Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). The major pathological changes are seen in centrilobular (zone 3) hepatocytes and adjacent endothelium. Glutathione (GSH) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury. Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury. We have prospectively studied the effect of glutamine supplementation during BMT. Thirty-four patients undergoing BMT were randomised to receive either glycl-L-glutamine (n = 18) or an isonitrogenous mixture of non-essential amino acids (n = 16). Glutamine was shown to significantly preserve protein C (days +4 and +7, P < 0.05) and albumin levels (days 0 and +4, P < 0.02). Markers of thrombin and plasmin generation (thrombin-antithrombin, prothrombin fragment F1+2 and plasmin-antiplasmin levels) were not significantly changed between the two groups. These findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during BMT. Previous studies have shown reductions in protein C, albumin, factor X and factor VII levels post BMT. Falling protein C levels have been shown to be predictive of severe VOD. These data suggest a role for glutamine in the protection of hepatic function following BMT. Data from animal studies suggests that glutamine supplementation may reduce the incidence or severity of cytotoxic-induced mucositis. This study examined the effect of glutamine supplements on mucositis in patients receiving bone marrow transplants. 24 patients were randomly assigned to receive an oral supplement of either glutamine or placebo (16 g/day) from the time of transplantation until discharge from hospital. There was no significant difference in the incidence of oral mucositis, assessed either by the patient (mucositis score: glutamine 17 vs. placebo 26.6) or an independent observer (glutamine 31.1 vs. placebo 32.3), or the number of days of diarrhoea (glutamine 3.1 vs. placebo 3.3 days). Similarly there were no significant differences in haematological indices (haemoglobin, WBC, platelets), the requirement for parenteral nutrition or hospital stay. Possible reasons for this negative result, which contrasts with those obtained in recent studies of patients receiving intravenous glutamine after bone marrow transplants, are discussed. Nutritional effects have traditionally focused on outcomes, such as nitrogen balance, wound healing, or muscle strength. Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient. Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance, we assessed the mood of individuals participating in a randomized controlled blinded trial receiving GLN solutions. Patients (n = 23) undergoing marrow transplantation were randomized by the research pharmacist to receive either standard total parenteral nutrition (TPN) (control) or GLN-containing TPN (40 g of glutamine total). The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50% of estimated requirements. Before TPN and on admission to the hospital, the patient completed the Profile of Mood States questionnaire, a standardized test quantifying the degree of tension, depression, anger, vigor, fatigue, and confusion. The patient completed the questionnaire again at the end of TPN near discharge. The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN. The scores for vigor in the control group (delta scores) decreased over the course of hospitalization as would be expected with a serious illness. The group receiving glutamine TPN, however, essentially showed little change in vigor from baseline and the delta score was significantly different from the control group (delta vigor score -0.85 +/- 2.1 in the glutamine group vs. -5.90 +/- 1.7 in the control group; p = .07).(ABSTRACT TRUNCATED AT 250 WORDS) In a randomized trial we studied the impact of providing total parenteral nutrition (TPN) to bone marrow transplant (BMT) patients during their cytoreductive therapy, and for 4 weeks following BMT, on 8 parameters of outcome. A total of 137 patients over 1 year of age and with normal nutritional status were randomized either to receive TPN starting one week prior to transplant or to receive hydration with a 5% dextrose solution containing electrolytes, minerals, trace elements, and vitamins. TPN was ultimately required by 40 of the 66 control patients when nutritional depletion was documented. Average total calorie and protein intake was significantly higher for the TPN group than for the control group. Minimum follow-up was 1 year and median was 2 years. Overall survival, time to relapse, and disease-free survival were significantly improved in the TPN group. Engraftment, duration of hospitalization, and incidences of acute and chronic graft-vs.-host disease and bacteremia were not different. Thus TPN during BMT had a positive effect on long-term outcome. Prophylactic nutritional therapy appears to be indicated even for well-nourished individuals during cytoreduction and BMT. Because all patients receiving bone marrow transplant (BMT) and peripheral blood progenitor cell transplant (PBPCT) experience gastrointestinal (GI) toxicity from the preparative regimen of chemotherapy, with or without radiation, oral glutamine was administered during the preparatory regimen and after transplant to maintain GI structure and function.
                To evaluate effects of oral glutamine on nutritional status and overall outcome, a prospective, randomized, double-blinded study was performed on 58 autologous and allogeneic BMT patients. Patients received 30 g of oral glutamine or placebo daily.
                The trends of decreased median length of stay and the median number of days of total parenteral nutrition (TPN) were seen in the group supplemented with the >0.285-g/kg (the recommended dosage) dose of glutamine; however, there was no statistically significant difference in the nutritional status and overall patient outcome as assessed by days receiving TPN, number of days required until oral intake resumed, length of hospitalization, number of days and highest grade of mucositis, and quantity and number of days of diarrhea.
                This study does not support the hypothesis that oral glutamine may offer benefit. Further investigation is required regarding clinical tools for determining effectiveness, administration for tolerance and compliance, dosage, and potential of oral glutamine usage. In a randomized, double-blind, prospective clinical trial, we evaluated the metabolic effects of glutamine-supplemented parenteral nutrition in patients with bone marrow transplants. We compared hospital charge and cost data for the two groups of patients in the trial.
                Retrospective review.
                Bone Marrow Transplant Unit, Brigham and Women's Hospital, Boston, Mass.
                Forty-three patients admitted to the Bone Marrow Transplant Unit were assigned randomly to receive either standard parenteral nutrition or an isocaloric, isonitrogenous parenteral nutrition solution containing glutamine starting on day 1 after bone marrow transplant. The two groups were well matched for diagnosis, antineoplastic treatment, and sex.
                The primary clinical end points evaluated were nitrogen balance, length of hospitalization, incidence of infection, and results of microbial culture. After completion of the study, we compared the hospital charges for the categories of room and board, surgery, laboratory, pharmacy, radiology, ancillary, and miscellaneous between the two groups of patients.
                The two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements. A P value of < .05 was considered significant.
                Nitrogen balance improved in the glutamine-supplemented group compared with control subjects (-1.4 +/- 0.5 g/day vs 4.2 +/- 1.2 g/day, respectively; P = .002). Length of hospitalization was significantly shorter in the glutamine-supplemented group than in the control group (29 +/- 1 day vs 36 +/- 2 days, respectively; P = .017). The incidence of positive microbial cultures and clinical infection was also significantly lower with glutamine supplementation. Hospital charges were $21,095 per patient less in the glutamine-supplemented group compared with charges for patients who received standard therapy. Room and board charges were significantly different: $51,484 +/- 2,647 for the glutamine-supplemented group vs $61,591 +/- 3,588 in the control group (P = .02).
                This intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital. A double-blind, randomized controlled trial was performed to determine the effect of glutamine (GLN)-enriched intravenous feedings on the volume and distribution of body fluids in catabolic patients. Subjects with hematologic malignancies in remission underwent a standard treatment of high-dose chemotherapy and total body irradiation before bone marrow transplantation. After completion of this regimen, they were randomized to receive either standard parenteral nutrition (STD, n = 10) or an isocaloric, isonitrogenous nutrient solution enriched with crystalline L-glutamine (0.57 g/kg/day, GLN, n = 10). Extracellular water (ECW) and total body water (TBW), determined by bromide and heavy water dilution techniques, were measured before the conditioning treatment and after termination of the intravenous feedings that were administered for 27 +/- 1 days. In addition electrical resistance (R, in ohms, omega) and reactance (Xc, omega) of the body to a weak alternating current were measured at these time points. Both study groups were comparable for age, weight, height, sex, and diagnosis. Initial TBW was highly related to electrical resistance (r = -0.93, p less than 0.001). After conditioning therapy, bone marrow infusion, and intravenous feedings, a 20% expansion in ECW was observed in the STD group (ECW: 18.0 +/- 1.1 L vs. 14.9 +/- 1.0, p = 0.012), and this fluid retention was associated with a marked decrease in electrical resistance (R: 514 +/- 28 omega vs. 558 +/- 26, p less than 0.05). In contrast the extracellular fluid compartment in patients receiving GLN-supplementation did not change (ECW: 15.8 +/- 0.9 L vs. 15.4 +/- 0.8, p = 0.49), and the body's resistance was maintained (R: 552 +/- 27 omega vs. 565 +/- 23, p = 0.42). Expansion of ECW could not be related to differences in fluid or sodium intake, or to the use of diuretics or steroids. Patients receiving the STD solution, however, exhibited a greater number of positive microbial cultures (p less than 0.01) and a higher rate of clinical infection compared with the GLN patients (5/10 vs. 0/10, p less than 0.05); the fluid expansion in infected STD patients was greater compared with uninfected individuals (delta ECW: + 5.0 +/- 1.4 vs. 0.7 +/- 0.5, p = 0.007). In this model of catabolic stress, fluid retention and expansion of the extracellular fluid compartment commonly observed after standard total parenteral nutrition can be attenuated by administering glutamine-supplemented intravenous feedings, possibly by protecting the host from microbial invasion and associated infection. Branched chain amino acids (BCAA) improve nitrogen balance and end-organ function in surgical patients, but are untested in marrow transplant recipients. We compared nitrogen balance, urinary 3-methylhistidine-to-creatinine ratio, upper arm anthropometry, serum prealbumin, and day to peripheral engraftment in a randomized, double-blinded trial between 45% (high-leucine) and 23% BCAA intravenous solutions in 40 adult leukemia patients for 1 month following allogeneic marrow transplantation. Nutritional support, provided at approximately 30 nonprotein calories/kg and 0.21 g nitrogen/kg ideal weight, did not differ between groups. Despite greater nitrogen loss and muscle breakdown evidenced by increased 3-methylhistidine-to-creatinine ratio and loss of arm muscle area by study end in the 45% BCAA, no statistical differences were observed when nitrogen balance was compared by week and within stress level as defined by organ and infectious complications. It is likely the patients in the 45% BCAA experienced greater metabolic stress by study end. Serum prealbumin and day posttransplant to peripheral engraftment also did not differ between groups. The chances (power) of this study exceeded 85% in detecting a difference in nitrogen balance of 2.5 g during study week 1 and 4.0 g during week 2. The power during week 3 was 77% for detecting a difference of 4.0 g, and it is unlikely that the true difference exceeds this magnitude. Thus, we did not find any evidence that intravenous BCAA-enriched solutions improved nitrogen balance during the first month after marrow transplantation. Twenty-nine patients undergoing bone marrow transplantation (BMT) were randomised prospectively to evaluate the effect of parenteral nutrition (TPN) on morbidity and mortality. Fourteen patients received a standard regimen of TPN for 10 +/- 4 days (mean +/- SD). All patients had free access to oral diet, which was significantly reduced compared to pre-transplant intake. In the TPN group, serum bilirubin by day 14 and serum bilirubin and gamma glutamyl transferase by day 21 were significantly higher than in the controls (p < 0.05). These differences probably reflect the higher incidence of serious pyrexia (T > 38.5' C) and blood culture positive rates in the TPN group. Weight loss in the control group was significantly greater than that of the TPN group (p < 0.05). TPN did not affect time to grafting or incidence of graft-versus-host disease. The use of TPN in the nutritional support of patients in small BMT units requires careful consideration.
In this update an additional study that compared PN and Glutamine versus standard PN showed that the certain benefits of parenteral nutrition with added glutamine compared to standard PN for reducing hospital stay are no longer definite. When PN with glutamine is compared with standard PN, patients may not leave hospital earlier, but do have reduced incidence of positive blood cultures, than those receiving standard PN. Where possible use of intravenous fluids and oral diet should be considered as a preference to parenteral nutrition, however, in the event of a patient suffering severe gastrointestinal failure even with a trial of enteral feeding, PN with the addition of glutamine could be considered.