• Assessment
    Is there a relationship between a patient's intake of dietary protein and the risk of acute graft-versus-host-disease associated with allogeneic hematopoietic cell transplant for hematologic malignancy?
    • Conclusion

      One study, a positive quality retrospective cohort analysis, found that oral protein intake within 17 days of allogeneic bone marrow transplant was associated with decreasing the risk of acute GVHD. A prospective randomized trial is needed to support to evaluate the role of protein intake in acute GVHD.

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between hematopoietic cell transplant and its long-term affect on the nutritional intake (calories, protein) of transplant survivors?
    • Conclusion
      One study, a neutral-rated, retrospective, descriptive study, found that patients with extensive chronic GVHD as a result of allogeneic HCT were twice as likely to consume less than 85% estimated caloric needs one-year after HCT as compared to patients with limited or no GVHD. Protein intake was not affected one-year post transplant.
    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between hematopoietic cell transplant and its affect on mineral intake/absorption of cancer patients?
    • Conclusion
      One small, randomized group trial (positive quality) found that patients undergoing autologous bone marrow transplant experienced negative balance for copper, zinc and calcium. More studies of mineral deficiencies as a result of bone marrow transplant are needed.
    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Are the calorie needs for cancer patients undergoing hematopoietic cell transplant different than the RDA?
    • Conclusion

      Two studies (one positive-quality longitudinal study and one positive-quality RCT) suggest that patients receiving HCT for hematologic malignancies require, on average, 35-40 kcal per kg per day to maintain nitrogen balance and body weight during the first month post-transplant. However, energy requirements may be higher during acute GVHD and for patients receiving > 75% of their total daily energy intake via PN. These studies evaluated patients receiving myeloablative allogeneic HCT, and energy needs may be different for patients receiving non-myeloablative and/or autologous HCT.

       

    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between hematopoietic cell transplant and its affect on the oral caloric intake of patients with hematologic malignancies?
    • Conclusion
      Three small studies (neutral-quality RCT, a positive-quality retrospective cohort and ) evaluated the oral intake of patients with hematologic malignancies undergoing BMT. Oral intake during BMT was less than required energy needs in all three studies. One study showed that the remission induction phase (versus consolidation and BMT phases) had a more prominent effect on the reduction of oral caloric intake. These studies observed that oral caloric intake was far below the required energy needs during the early post-transplant period.
    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Are the protein requirements of patients with hematological malignancies undergoing hematopoietic cell transplant different than the RDA?
    • Conclusion
      Three studies (one neutral quality timeseries, one positive quality RCT, and one negative quality longitudinal study) assessed the protein requirements of patients undergoing HCT in order to maintain positive nitrogen balance in the post-transplant period. Although studies assess the needs of patients with hematological malignancies, the type of transplant varies within and among studies. T wo of these studies did not reach nitrogen balance with protein intakes of 1.2 g protein per kg to 1.7 g protein per kg. The one study that did reach nitrogen balance provided 2.2 g protein per kg. Although these studies indicate that the needs of patients undergoing HCT are higher than the RDA, more research is needed to identify more defined recommendations for actual grams of protein required. The patients in the above mentioned studies received myeloablative HCT regimens. More recently non-myeloablative HCT has begun to replace this earlier form of HCT. The protein needs of patients may be different with non-myeloablative HCT.
    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: Protein Needs vs. RDA: HCT 2006
       
  • Intervention
    Does the use of oral glutamine improve tolerance and support recovery from hematopoietic cell transplantation (HCT) among individuals with hematologic malignancies?
    • Conclusion

      Two(2) RCTs (1 positive quality, 1 neutral quality) all found that 16-30g glutamine per day orally is not effective in preventing diarrhea, improving oral intake or decreasing PN requirements, decreasing the need for pain medications, decreasing incidence of infectious complications, decreasing LOS, or improving survival in patients with hematologic malignancies receiving autologous or allogeneic HCT. The timing, dosage and method of administration of the glutamine all varied in these studies. Further trials are needed to clarify the relationship.

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: Glutamine and Symptoms/Complications 2005
       
    Is the use of oral glutamine to decrease incidence or severity of oral mucositis associated with hematopoietic cell transplantation (HCT) for patients with hematological malignancies?
    • Conclusion

      Two (2) RCTs (1 positive quality, 1 neutral quality) found that 16-30g glutamine per day orally is not effective in decreasing the incidence or severity of oral mucositis associated with autologous or allogeneic hematopoietic cell transplantation for patients with hematologic malignancies. The timing, dosage and method of administration of oral glutamine all varied in these studies. Further trials are needed to clarify the relationship.

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: Glutamine and Symptoms/Complications 2005
       
    Is there a relationship between the intake of parenteral glutamine to improve tolerance and support recovery from a patient undergoing hematopoietic cell transplant (HCT) and the reduction of diarrhea associated with treatment?
    • Conclusion

      One meta-analysis (positive quality), that included 3 studies with 103 patients, did not find parenteral glutamine to be effective in reducing diarrhea in HCT patients.

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: Glutamine and Symptoms/Complications 2005
       
    Is there a relationship between the use of parenteral glutamine by patients to improve tolerance and support recovery from hematopoietic cell transplant (HCT) and the reduction of mucositis associated with treatment?
    • Conclusion

      One positive quality meta-analysis (3 studies with 103 patients) and one positive quality RCT reported no benefit of parenteral glutamine for the prevention/reduction in mucositis. One additional RCT found a statistically significant difference in peak mucositis scores, but not duration of mucosits, when comparing those who received parenteral glutamine with those who received placebo. All of the studies were limited by small sample size. The dosing, administration and timing of glutamine supplementation varied for the studies as well. Further studies are needed.

    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: Glutamine and Symptoms/Complications 2005
       
    Is there a relationship between the use of parenteral nutrition vs. control to reduce symptoms and support recovery and the reduction of symptoms associated with inpatient treatment for hematopoietic cell transplant?
    • Conclusion

      Four studies (1 RCT of neutral quality; 1 nonrandomized clinical trial of positive quality; 2 retrospective cohort studies of positive quality) found that PN should be used only in appropriately selected HCT patients due to an increased risk of treatment complications associated with PN as well as a lack of significant differences in long-term outcomes.  Criteria for patient selection for PN includes malnutrition and/or severe GI dysfunction.  Differences in types of studies and patient populations studied, differences in PN regimens, study design flaws, varying types of cancers studied, varying types of conditioning regimens used, and variations in type of transplant make it difficult to compare studies and draw conclusions.  Further research is needed to determine the best use of PN in HCT patients.

       

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between the use of parenteral nutrition vs. control to reduce symptoms and support recovery and the reduction of symptoms associated with outpatient treatment for hematopoietic cell transplant?
    • Conclusion

      One (1) + quality randomized, controlled trial (Charuhas et al, 1997) found that outpatient PN delays resumption of oral intake (p = 0.049), and that use of IV fluids for hydration as an alternative to PN does not have adverse patient outcomes in terms of weight loss, hospital readmissions, relapse of malignancies, or survival to 150 days post-transplant.  Although weight loss was statistically greater (p = 0.004) for the IV fluids group, the amount lost was not clinically significant.  Costs associated with provision of IV fluids were substantially less than costs of providing PN.  Charuhas et al. concluded that PN should be reserved for HCT outpatients who exhibit severe GI malfunction.  Further study is needed to determine the most appropriate use of PN in outpatient treatment for HCT.

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between the use of parenteral nutrition vs. control to reduce symptoms and support recovery and the reduction of symptoms associated with inpatient treatment for hematopoietic cell transplant for breast cancer patients?
    • Conclusion

      One neutral quality RCT found that while prophylactic PN preserved nutritional status and lean body mass better than oral diet in well-nourished breast cancer patients undergoing auto-HCT, there were no differences found in LOS or survival between the two groups.   The researchers concluded that well-nourished breast cancer patients who have no major complications or prolonged poor oral intake will probably not benefit from PN while undergoing auto-HCT.  Because of its expense and risk for infectious complications, PN should be used in appropriate breast cancer patients only. 

       

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between the use of parenteral nutrition vs. control to reduce symptoms and support recovery and the reduction of symptoms associated with inpatient treatment for allogeneic hematopoietic cell transplant?
    • Conclusion

      One cost-benefit analysis (negative quality) found that PN did not result in significantly improved outcomes for allo-HCT patients.  Parenteral nutrition was associated with increased rates of infection and subsequently higher costs.  The researchers concluded that intensive nutritional monitoring to eliminate unnecessary PN can result in significant cost savings for allo-HCT providers.

       

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between a patient's increased protein intake via total parenteral nutrition to improve tolerance and support recovery from hematopoietic cell transplant and the reduction of complications associated with hematopoietic cell transplant?
    • Conclusion
      One small, positive quality, randomized trial compared the use of standard nitrogen TPN to high-nitrogen TPN, with equal caloric values and found that the high-nitrogen formula better preserved nitrogen balance without causing clinical complications. No other positive findings were noted. Larger trials are needed to find statistical significance in other clinical outcomes.
    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between a patient's intake of branched chain amino acid-enriched total parenteral nutrition to improve tolerance and support recovery from hematopoietic cell transplant (HCT) for hematologic malignancy, and the reduction of complications associated with HCT?
    • Conclusion

      One randomized, double-blinded positive quality study evaluated the use of BCAA-enriched PN in patients receiving HCT for hematologic malignancies. No differences in treatment related complications (sepsis, fever, GVHD, elevated LFTs, steroid requirements, pneumonia, nitrogen balance) or outcomes (time to engraftment, resumption of oral intake) were observed between patients receiving 23% BCAA and 45% BCAA-enriched PN solutions. 

       

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between a patient's nutritional intake (protein and calories) from total parenteral nutrition as compared to peripheral parenteral nutrition to improve tolerance and support recovery from hematopoietic cell transplant (HCT), and the reduction of complications associated with HCT?
    • Conclusion
      Three studies (one positive quality prospective randomized group trial, one neutral quality retrospective cohort, and one neutral quality non-randomized study) compared the effectiveness of using TPN vs. PPN in the post-BMT period. The nutritional content of the solutions, duration of nutritional supplementation, consideration and quantification of ad lib oral intake, type of malignancy, and differing cancer treatment regimens (autologous vs. allogeneic cell transplantation) varied among the studies. Evaluation of outcomes is further limited by small sample size (2 studies) and poor study design (2 studies) and limited data reported (1 study). The only study, although limited by small sample size, that had similar calorie and protein intake in both TPN and PPN/EN solutions (25 g N/day and 136:1 calorie:nitrogen) showed that either solution was effective in supporting recovery from bone marrow transplant by maintaining body weight and nitrogen balance without causing additional complications. The other two studies had inadequate nutritional support in the PPN solution and the results varied (one favored TPN, the other PPN). A larger, prospective randomized trial with equivocal nutritional content in TPN and PPN solutions and similar treatment regimens is needed.
    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006
       
    Is there a relationship between the use of a lipid-based TPN solution to improve tolerance and support recovery in hematopoietic marrow transplant patients, and the reduction of complications associated with hematopoietic marrow transplant?
    • Conclusion
      Two randomized trials (positive quality) noted no significant differences between a standard lipid-based TPN solution to TPN solution with little or no lipids for time to engraftment, disease relapse, incidence of infection, and incidence and time to onset of graft-versus-host disease in patients undergoing hematopoietic marrow transplant for hematologic malignancy. The larger trial (512 patients) focused on controlling blood glucose to <200 mg/dL and therefore did not have evidence of hyperglycemia, while the smaller study (66 patients) did not maintain glucose levels at <200 mg/dL and had incidence of hyperglycemia.
    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Search Plan and Results: HCT: Calories, Protein, Lipids, Nutritional Intake, EN/PN 2006