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Title: Reduced plasma amino acid levels during allogeneic haematopoietic stem cell transplantation are associated with systemic inflammation and treatment-related complications

Author
item WEISCHENDORFF, SARAH - Rigshospitalet - Copenhagen University Hospital
item KIELSEN, KATRINE - Rigshospitalet - Copenhagen University Hospital
item NEDERBY, MARIA - University Of Copenhagen
item SVENDSEN, LOTTE - University Of Copenhagen
item Burrin, Douglas - Doug
item HEILMANN, CARSTEN - Rigshospitalet - Copenhagen University Hospital
item IFVERSEN, MARIANNE - Rigshospitalet - Copenhagen University Hospital
item SENGELOV, HENRIK - Rigshospitalet - Copenhagen University Hospital
item MOLGAARD, CHRISTIAN - University Of Copenhagen
item MULLER, KLAUS - Rigshospitalet - Copenhagen University Hospital

Submitted to: Biology of Blood and Marrow Transplantation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2019
Publication Date: 3/15/2019
Citation: Weischendorff, S., Kielsen, K., Nederby, M., Svendsen, L., Burrin, D.G., Heilmann, C., Ifversen, M., Sengelov, H., Molgaard, C., Muller, K. 2019. Reduced plasma amino acid levels during allogeneic haematopoietic stem cell transplantation are associated with systemic inflammation and treatment-related complications. Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2019.03.018.
DOI: https://doi.org/10.1016/j.bbmt.2019.03.018

Interpretive Summary: Many patients that develop blood cancers are treated with radiation and chemotherapy which destroys their immune system. In order to restore the immune system, these patients receive a transplant of stem cells from a match donor, usually taken from bone marrow of a relative. After stem cell transplantation, these patients sometimes experience poor outcomes because of gastrointestinal toxicity, increased metabolic rate and muscle wasting. The purpose of this human clinical study was collect blood samples from 80 children and adult patients to test whether changes in the circulating amino acid concentrations before and after bone marrow transplantation correlate with treatment complications. The results showed that the concentration of several amino acids are lower than normal in patients that develop complications from bone marrow transplantation, such as immune rejection of transplanted immune cells. These results suggest that targeted amino acid supplementation should be consider to improve the nutrition status in bone marrow transplant patients.

Technical Abstract: Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged by cytotoxic effects of the conditioning regimen, resulting in tissue damage, systemic inflammation and elevated metabolic demands for amino acids to regenerate damaged tissues, reconstitute hematopoietic cells, and establish antioxidant defenses. Few studies have addressed the role of plasma amino acid (PAA) levels during transplantation, and it remains unknown if amino acid deficiency can aggravate treatment related morbidity. We determined plasma levels of the 23 human amino acids in 80 HSCT patients (age 1.1-55.4 years) before conditioning and on day +7 and +21 post-transplant along with C-reactive protein (CRP) and Interleukin 6 (IL-6) levels on day +7. Significant changes were observed in plasma concentrations of several human amino acids during HSCT. On day +7, several amino acids were inversely correlated with both CRP and IL-6, including glutamic acid, serine, alanine, glutamine, arginine, cysteine, glycine, histidine, lysine, tryptophan, threonine, taurine, proline, and methionine (r between -0.22 and -0.66, all p<0.05). Patients developing sinusoidal obstruction syndrome (SOS) had significantly lower total PAA levels compared to patients without SOS (2013 ng/l (1709-2318) vs 2706 ng/l (2261-3150), p=0.006) along with lower individual levels of glutamic acid, serine, arginine, glycine, lysine, valine, tryptophan, threonine, and proline (all p<0.05) on day +7. Patients with severe acute graft-versus-host disease had lower total PAA level (1922 ng/l (1738-2106) vs 2649 ng/l (2244-3055), p=0.014) and decreased levels of serine, glutamine, cysteine, glycine, lysine and threonine on day +7 (all p<0.05). These results indicate a relationship between low concentrations of certain amino acids and risk of treatment-related complications.