Saundra N. Aker

Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition

Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition. To determine if muscle atrophy could be minimized with exercise therapy, 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive: (1) no therapy (controls), (2) physical therapy thrice weekly (PT3), or (3) physical therapy five times weekly (PT5). Patients were studied through 35 days posttransplant. Muscle protein status and turnover was assessed by weekly nitrogen balance, and creatinine and 3-methylhistidine excretion. Results favored a muscle protein-sparing effect of exercise, as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity. Changes in arm muscle area correlated with energy, but not protein intake. Large individual variation, inadequate nutritional support and differences in admission arm muscle area may have clouded these results.

A Double-Blind Randomized Trial Comparing Outpatient Parenteral Nutrition With Intravenous Hydration: Effect on Resumption of Oral Intake After Marrow Transplantation

BACKGROUND 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. METHODS 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 patients oral intake met > or = 85% caloric requirements for 3 consecutive days. RESULTS 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. CONCLUSIONS We conclude that outpatient PN delays resumption of oral intake and that its replacement with hydration solution does not result in adverse patient outcome.

Body composition changes in marrow transplant recipients receiving total parenteral nutrition

Nine patients with acute lymphocytic leukemia in remission, aged 12–35 years, undergoing allogeneic bone marrow transplantation (BMT) were studied for changes in body fluid balance and body composition. Body composition and fluids were assessed the first 4 weeks following BMT, using isotope dilution and anthropometry. Oral and parenteral nutrient intakes were recorded daily. Tracer dilution techniques were used to assess body fluid volumes and estimate body cell, lean body, and body fat masses. Body cell mass was lost (mean −1.62 kg, P < 0.05) without significant changes in body fat or lean body masses. There was an expansion of the extracellular fluid compartment (mean +0.8 l, P < 0.05) and a loss in the intracellular fluid compartment (mean −1.3 l, P < 0.05) with little change in total body water volume. Changes in body weight correlated poorly with body cell mass or fluid volume changes. Change in arm muscle area correlated well with changes in body cell mass (r = 0.61, P < 0.05) and lean body mass (r = 0.68, P < 0.05), while that of arm fat area did not reflect its isotope dilution‐derived counterpart. Instead, the change in arm fat area was related to shifts in fluid compartments. Prealbumin decreased significantly (mean −9.3 mg/dl, P < 0.05), while albumin decreased slightly (mean −0.1 mg/dl), and both were related to changes in body cell mass. Nitrogen balance was negative throughout the study and the overall mean was related to the change in body cell mass (r = 0.60, P < 0.05). Calorie and protein intakes were not associated with the changes in body composition, implying other causal factors.

The Use of Sterile and Low Microbial Diets in Ultraisolation Environments

The evidence for the use of sterile and low microbial diets in ultraisolation environments is reviewed. Studies have suggested that sterile food is not required for gut sterilization when oral nonabsorbable antibiotics are used, but if a low microbial food contains an antibiotic-resistant organism, colonization can occur. There may be a beneficial effect on the incidence of infection by serving pathogen-free foods, either sterile or low microbial, to the immunosuppressed patient regardless of type of environment, yet the comparative effectiveness of sterile and low microbial diets in preventing introduction of new pathogens accessing the host via the mouth, oropharynx, and esophagus has not been systematically evaluated.

Prolonged anorexia and elevated plasma cytokine levels following myeloablative allogeneic hematopoietic cell transplant

Myeloablative conditioning regimens commonly lead to prolonged anorexia and poor oral intake. In a prospective study of 147 patients receiving CY, total body irradiation and allogeneic hematopoietic cells, we determined the extent of decline in oral intake and assessed plasma cytokine levels and development of acute GVHD as explanations for protracted anorexia. For each patient, daily oral caloric intake was expressed as a percent of estimated basal requirements, calculated as basal energy expenditure, through day 20. Oral caloric intake was significantly reduced in 92% of patients and remained low. The nadir in oral intake occurred at days 10–12, when median oral caloric intake was 3% of basal energy requirements. Plasma cytokines known to affect appetite (IL2, IL6, tumor necrosis factor-alpha) were significantly elevated above normal following conditioning therapy (P<0.001 for each cytokine). Acute GVHD did not appear to affect oral intake to transplant day 20 in this cohort of patients; however, plasma levels of IL6 rose steeply before the clinical onset of GVHD. Persistent fever occurred with the greatest frequency in patients with most profound reduction in oral intake. We conclude that prolonged alterations in oral intake following this myeloablative regimen may be related to circulating cytokines known to alter eating behavior.

Impact of a randomized, controlled trial of liberal vs conservative hospital discharge criteria on energy, protein, and fluid intake in patients who received marrow transplants.

OBJECT To determine if adult patients who received marrow transplants had faster resumption of oral energy and nutrient intake and shorter duration of intravenous (i.v.) fluid requirement if discharged from the hospital earlier than is customary. DESIGN Randomized, controlled trial of patients remaining hospitalized because of inadequate oral intake. Consenting patients were assigned randomly to remain hospitalized (hospital group) or be discharged to an ambulatory setting (ambulatory group). SUBJECTS Seventy-eight patients of the Fred Hutchinson Cancer Research Center who were consuming less than 33% of estimated energy requirement and requiring up to 3,000 mL of fluids per day intravenously. INTERVENTION Participants received nutrition counseling by a registered dietitian to promote resumption of oral intake. Daily oral intake records were analyzed to determine energy and nutrient content. MAIN OUTCOME MEASURES Days after study enrollment to consume 33% of energy and protein requirements and total number of days of i.v. fluid support were analyzed by group until discharge from the center, approximately 100 days after transplantation. STATISTICAL ANALYSES Demographic data were defined by group means. Differences between treatment procedures were determined by Cox regression analysis. No variables were confounding. RESULTS The hospital group took fewer days than the ambulatory group to resume oral energy intake (4.5 vs 8.0, P = .004) and to discontinue i.v. fluids (30.5 vs 48.5, P = .019). There was no difference between groups in days of parenteral nutrition support (P = .817) or days to resume oral protein intake (P = .470). APPLICATIONS/CONCLUSIONS Oral and gastrointestinal complications delay resumption of oral energy and protein intakes after transplantation. Earlier hospital discharge can achieve cost savings but may delay resumption of oral energy intake. Because of continued high-risk nutrition status and potential for rapid change in medical status, nutrition assessment and counseling are necessary in both the hospital and ambulatory setting to promote resumption of oral intake and discontinuation of i.v. fluids.

Intravenous Branched Chain Amino Acid Trial in Marrow Transplant Recipients

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.

Nutrient Support in Hematopoietic Cell Transplantation

High-dose cytoreduction and hematopoietic stem cell infusion form the basis for treatment of hematologic cancers, defects or failure of hematopoiesis, and some solid tumors. As an antitumor therapy, allogeneic hematopoietic cell transplantation (HCT) is superior to autologous HCT by induction of a graft-vs-tumor effect. However, recipients of allografts suffer higher transplant-related mortality owing to graft-vs-host disease (GVHD). Nutrition support research must recognize that HCT is a heterogeneous modality whose short and long-term outcomes are affected by transplant type, preparative regimens, diagnosis, disease stage, age, and nutritional status. The field of HCT will diversify further as lower dose cytoreduction and mixed chimerism grafts allow expansion of the technique to older patients and to other diseases.

Oral feedings in the cancer patient.

The importance of maintaining the cancer patients nutritional status is now recognized as a major part of the medical care. It is necessary for the oncology team to be aware of the psychological and physiological factors that interfere with food acceptance so that the correct food can be offered at the right time in the most palatable form. The oral route is the preferred method of feeding, and nutritional supplements, chosen according to the individual patients needs, are of great value in assuring an adequate oral intake. Diagnostic tests and therapy are frequent causes of disruption of the meal schedule and the dietary service must be flexible in providing the patient an opportunity to make up for missed meals. Taste disturbance, nausea, vomiting and mucositis caused by therapy may necessitate periods of intravenous hyperalimentation. Food aversions due to therapy can frequently be prevented by avoiding new or unusual foods in the hours before chemotherapy or irradiation. Regular nutrition counseling during clinic visits and/or hospitalization permits diet modification for specific therapeutic needs. The ultimate goal is the prevention of wasting and debilitation due to malnutrition in the cancer patient.

Primary Taste Thresholds in Children with Leukemia Undergoing Marrow Transplantation

Taste threshold for the four basic tastes were determined to assess taste impairments in 11 children with acute leukemia undergoing marrow transplantation and in 20 normal children. Thresholds were measured on admission, 2 days, and 45 days after transplant using the Up-Down Staircase method. No significant difference was noted between patients at admission and the control group for sweet, bitter, or salt. There was a significant difference between patients and controls for the sour threshold (p = 0.006). Patient threshold values on day 2 and day 45 (posttransplant were compared with admission values. No significant differences were seen, except for the salt threshold which was increased at day 2 posttransplant when compared with the admission values. We conclude that only minor changes in taste thresholds were demonstrated in this study. These changes probably do not account for abnormal food tastes reported by patients.