Glutamine Dipeptide Enriched Parenteral Nutrition Significantly Increase Short-Term Survival after HLA-Identical Allogeneic Stem Cell Transplantation.
Authors: Torres Henrique O.G. , Vilela Eduardo G. , Cunha Aloisio S. , Goulart Eugenio M.A. , Souza Marcelo H.C. , Aguirre Ana Carolina C. , Azevedo Wellington M. , Lodi Fernanda M. , Bittencourt Henrique N.S. 
Published: April 2020

Abstract
Sixty-one consecutive patients with hematologic malignancies submitted to HLA-identical sibling allogeneic stem cell transplantation (allo-SCT) were followed in order to evaluate the relationship between the use of glutamine as part of parenteral nutrition (PN) and death/complications related to the procedure. Patients were randomly and blindly assigned to receive either glutamine enriched PN (group 1) or regular PN (group 2). The glutamine dipeptide (Dipeptiven® - Fresenius Kabi) was associated with parenteral nutrition in the first week following transplantation (D0−D+6). Infectious complications, acute GVHD, length of stay (LOS), deaths on D+100 and D+180 and, when possible, intestinal permeability as measured by urinary excretion of lactulosis and mannitol (on admission, D+6 and D+14) were the end-points. Eight patients were excluded from randomization because they refuse to take glutamine or glutamine was not available on D0, but were followed and analyzed as controls, so that group 1 comprised 27 patients and group 2 thirty-four (26+8). Demographics did not differ between groups (age - 37 ± 11 versus 36 ± 8.7, and gender - 14 versus 18 females). Diseases (CML n=37; AML n=12; ALL n=7; MDS n=4; MM n=1) were equally distributed between groups. Patients on group 1 received an average of 23.4g of glutamine/day, corresponding to 49% of the average protein delivery through PN (total 47.9g, against 50 g/day on group2, NS). They were allowed to eat ad libitum. Infection and acute GVHD incidences, and LOS median (36 versus 36.5) were similar on both groups. Intestinal permeability, which showed to be already affected on admission, was not affected by the use of glutamine, but consistently worsened throughout the study, from admission to D+14. Transplant-related mortality (TRM) rate was 29.5% on D+100 (18 deaths, 4 on group 1 and 14 on group 2) and 40.1% on D+180 (25 deaths, 7 on group 1 and 18 on group 2). Survival analysis showed statistical difference on univariate analysis, with a better survival for Group 1 both on D+100 (p= 0.02, log-rank) and D+180 (p=0.02). A Cox regression model was applied using variables that showed a p value of less than 0.2 (diagnosis-related risk, graft source - peripheral blood or bone marrow, conditioning regimen and use of glutamine). Use of glutamine, both on D+100 (HR 6.4; CI95% 1.81–22.44 - p=0.004) and D+180 (HR 4.9; CI95% 1.76–13.61 - p=0.002) was associated with a significantly higher chance of survival. Statistical significance is maintained if the cases excluded from randomization are also excluded from analysis. The results showed that glutamine dipeptide enriched PN plays a role on increasing short-term survival after allo-SCT. Benefits of glutamine dipeptide seems to be independent of mucosal damage/recovery, at least on short term, as intestinal permeability between admission and D +14 was not affected by its use.