Monthly Key Publication Reviews

Publication: Andersen, S., Fichera, R., Banks, M. et al. Proactive enteral nutrition for patients undergoing allogeneic stem cell transplantation - implementation and clinical outcomes. Eur J Clin Nutr 78, 251–256 (2024). https://doi.org/10.1038/s41430-023-01367-8. 

Reviewer: Valentina Da Prat, MD, ASPEN Global Parenteral Nutrition Fellow 2024

Why is This Paper Important: Clinicians managing the nutritional support of patients undergoing allogeneic bone marrow transplantation (ASCT) face significant difficulties related to the high burden of persistent post-ASCT nutrition impact symptoms, such as mucositis1. As a result, a large proportion of patients undergo parenteral nutrition (PN), which may carry some risks in the immunocompromised and often hyperglycemic, hyperlipemic, and/or volume overloaded ASCT patients2. Previous studies have shown that enteral nutrition (EN) is associated with a reduced risk of graft-versus-host disease (GvHD), improved gut microbial homeostasis, and increased survival rates compared to PN3,4. Despite this, there is a lack of shared protocols for the implementation of EN in ASCT patients.

Summary: This study is divided into two phases. In the first phase, the authors conducted a staff survey, which revealed that the main barriers to the use of EN in ASCT patients include uncertain EN tolerance, lack of confidence in nasogastric tube (NGT) placement, and inadequate training and resources. In the second phase, the authors developed a nutrition support algorithm based on proactive EN or on-demand nutrition support according to the ASCT conditioning regimen: 

  • in patients undergoing myeloablative/reduced intensity conditioning, NGT placement is performed the day after ASCT after achieving an adequate platelet count (30,000/mm3 in this study) and proactive EN is started at a low rate (30 mL/h) with a fiber-free, high-protein, 1.25 kcal/mL polymeric formula and gradually incremented as oral intake decreases;
  • in patients undergoing non-myeloablative conditioning, EN is initiated only when food intake decreases and oral nutritional supplements are ineffective despite symptomatic therapy.

Of 99 patients receiving myeloablative/reduced intensity conditioning, 84 (84.8%) were started on proactive EN, which was continued as the only artificial nutrition support in 61 (72.6% of patients receiving EN). In the remaining cases, EN had to be discontinued due to enterocolitis, NGT dislodgement/obstruction, or EN intolerance. Patients receiving EN alone (n=61) compared to patients receiving PN (n=36) had a significantly shorter length of stay (median 19 vs. 22 days, p=0.012), improved nutritional status at discharge (rate of well-nourished patients according to the Subjective Global Assessment 96% vs. 71%, p=0.005), and increased survival (patients alive at day 100 95% vs. 81%, p=0.036). 

Commentary: After attempting to identify the main barriers to EN implementation through a survey, the authors provided an interesting algorithm for nutritional support ASCT patients, suggesting that severe mucositis may not be a contraindication to EN if proactively started immediately after ASCT. Indeed, the authors were able to keep almost two thirds of the patients PN-free. However, there are potential biases regarding the impact of EN on clinical outcomes. First, the two populations have significant differences in conditioning regimens and baseline nutritional status, which may have contributed to worse clinical outcomes in the PN group; unfortunately, data on comorbidities and baseline laboratory parameters are not available. Second, the sample size may be inadequate for certain outcomes, and multivariable analyses were not performed due to the relatively small number of patients. Third, clinical outcomes may have been influenced by differences in energy and protein delivery in the two groups, but no comparison is available regarding the actual calorie and nutrient load provided to patients. 

Despite these biases and some potentially interesting outcomes not evaluated (e.g., infectious complications) and key definitions missing (e.g., clear criteria for EN intolerance), this study provides a thought-provoking and inspiring example of how nutritional support for ASCT patients can be improved. 

References:

  1. Urbain P, Birlinger J, Lambert C, Finke J, Bertz H, Biesalski HK. Longitudinal follow-up of nutritional status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2013;48(3):446-451. doi:10.1038/BMT.2012.158
  2. Soussi MA, Besbes H, Mellouli F, et al. Parenteral Nutrition Complications in Children Undergoing Bone Marrow Transplantation. J Pediatr Hematol Oncol. 2019;41(7):E473-E477. doi:10.1097/MPH.0000000000001560
  3. Beckerson J, Szydlo RM, Hickson M, et al. Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies. Clin Nutr. 2019;38(2):738-744. doi:10.1016/j.clnu.2018.03.008
  4. Zama D, Gori D, Muratore E, et al. Enteral versus Parenteral Nutrition as Nutritional Support after Allogeneic Hematopoietic Stem Cell Transplantation: a Systematic Review and Meta-Analysis. Transplant Cell Ther. 2021;27(2):180.e1-180.e8. doi:10.1016/j.jtct.2020.11.006
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