Malnutrition Prevention after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT): A Prospective Explorative Interventional Study with an Oral Polymeric Formulation Enriched with Transforming Growth Factor Beta 2 (TGF-β2)

Abstract

Malnutrition is common after allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT), and interventions directed to correct nutritional status are warranted to improve transplant outcomes. In this prospective study, an oral polymeric formulation enriched with TGF-β2 (TE-OPF) was explored to correct malnutrition according to Patient-Generated Subjective Global Assessment (PG-SGA). TE-OPF was proposed to 51 consecutive patients who received transplants at our institution for hematological malignancies, and sufficient dose intake was established per protocol as at least 50% of the prescribed dose of TE-OPF: group A received adequate nutritional support; group B, inadequate. The study met the primary outcomes in terms of safety (no adverse events reported during TE-OPF intake except for its disgusting taste) and malnutrition (PG-SGA C 28 days after transplant): severely malnourished patients (PG-SGA C) accounted for 13% in group A and 88.9% in group B (p = 0.000). At the end of the study, after a median follow-up of 416 days, the estimated median Overall Survival (OS) was 734 days for well or moderately nourished patients (PG-SGA A/B) in comparison to 424 for malnourished patients (p = 0.03). Inadequate TE-OPF intake was associated with an increase in acute gastrointestinal Graft Versus Host Disease (GVHD) cumulative incidence (38% vs. 0% p = 0.006). A higher incidence of pneumonia was reported in group B (p = 0.006). IGF-1 levels at 14 and 28 days after transplant were significantly higher in group A and were associated with a lower incidence of acute GVHD (aGVHD). Higher subsets of B, T, and NK cells were found in group A, and a higher number of CD16+ NK cells was associated with a lower incidence of acute GVHD (p = 0.005) and increased survival at the end of the study (p = 0.023). Artificial neural network analysis suggested that inadequate TE-OPF intake, pneumonia, and sepsis significantly affected malnutrition 28 days after alloHSCT and survival 365 days after alloHSCT (normalized importance 100%, 82%, and 68%, respectively). In this exploratory and preliminary study, the use of TE-OPF appeared to reduce the incidence of malnutrition after alloHSCT, but larger and controlled studies are required.