Thomas Hueso1, Jordan Gauthier2, Marie Joncquel Chevalier-Curt3, Leonardo Magro2, Valérie Coiteux2, Rémy Dulery2, Benjamin Carpentier2, Julien Labreuche4, Gandhi Damaj5, Ibrahim Yakoub-Agha6, David Seguy7. 1. University of Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Lille, France; Normandie University, UNICAEN, CHU Caen, Department of Clinical Hematology, Caen, France. 2. University of Lille, CHU Lille, Stem Cell Transplantation Unit, Department of Hematology, Lille, France. 3. University of Lille, CHU Lille, Department of Biochemistry and Molecular Biology, Laboratory of Hormonology, Metabolism-Nutrition & Oncology, Center of Biology and Pathology, Lille, France. 4. University of Lille, CHU Lille, Department of Biostatistics EA 2694, Lille, France. 5. Normandie University, UNICAEN, CHU Caen, Department of Clinical Hematology, Caen, France. 6. University of Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Lille, France; University of Lille, CHU Lille, Stem Cell Transplantation Unit, Department of Hematology, Lille, France. 7. University of Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Lille, France; University of Lille, CHU Lille, Department of Nutrition, Lille, France. Electronic address: david.seguy@univ-lille.fr.
Abstract
BACKGROUND & AIMS: The gastrointestinal form of acute graft vs host disease increases morbidity and mortality following allogeneic hematopoietic cell transplantation. Plasma levels of citrulline, a non-proteinogenic amino acid, indicate functional enterocyte mass. We measured citrulline in patients before allogeneic hematopoietic cell transplantation and investigated its association with incidence and severity of gastrointestinal graft vs host disease. METHODS: We performed a retrospective study with 191 patients (69 women, 122 men; median age of 52 years) who underwent allogeneic hematopoietic cell transplantation for hematological malignancies at a tertiary center of France from January 2013 through April 2015. Levels of citrulline in plasma samples collected 30 days before graft infusion were measured by high performance liquid chromatography with tandem mass spectrometry. We assigned patients to groups with a high level of citrulline (>26 μmol/L) or low level of citrulline (≤26 μmol/L). The primary outcomes were difference between groups in incidence of stage 2-4 gastrointestinal graft vs host disease, death without hematological disease relapse (non-relapse mortality), relapse of the hematological disease, and overall survival through 2 years after transplantation. RESULTS: Ninety-six patients (50%) developed acute graft vs host disease and 37 (19%) developed a gastrointestinal form. Among patients with gastrointestinal involvement, 33 patients (89%) had stage 2-4 gastrointestinal graft vs host disease. In univariable analysis, low level of citrulline associated with higher cumulative incidence of stage 2-4 gastrointestinal graft vs host disease, non-relapse mortality, and shorter overall survival. In multivariable analysis, low level of citrulline was the only risk factor independently associated with stage 2-4 gastrointestinal graft vs host disease (hazard ratio, 3.06; 95% CI, 1.37-6.85; P = .007); it also associated with increased non-relapse mortality (hazard ratio, 2.29; 95% CI, 1.24-4.22; P = .008). CONCLUSIONS: In a retrospective study with 191 patients, we associated a low plasma level of citrulline before allogeneic hematopoietic cell transplantation with a higher risk for stage 2-4 gastrointestinal graft vs host disease and non-relapse mortality. This marker might be used to manage patients before allogeneic hematopoietic cell transplantation.
BACKGROUND & AIMS: The gastrointestinal form of acute graft vs host disease increases morbidity and mortality following allogeneic hematopoietic cell transplantation. Plasma levels of citrulline, a non-proteinogenic amino acid, indicate functional enterocyte mass. We measured citrulline in patients before allogeneic hematopoietic cell transplantation and investigated its association with incidence and severity of gastrointestinal graft vs host disease. METHODS: We performed a retrospective study with 191 patients (69 women, 122 men; median age of 52 years) who underwent allogeneic hematopoietic cell transplantation for hematological malignancies at a tertiary center of France from January 2013 through April 2015. Levels of citrulline in plasma samples collected 30 days before graft infusion were measured by high performance liquid chromatography with tandem mass spectrometry. We assigned patients to groups with a high level of citrulline (>26 μmol/L) or low level of citrulline (≤26 μmol/L). The primary outcomes were difference between groups in incidence of stage 2-4 gastrointestinal graft vs host disease, death without hematological disease relapse (non-relapse mortality), relapse of the hematological disease, and overall survival through 2 years after transplantation. RESULTS: Ninety-six patients (50%) developed acute graft vs host disease and 37 (19%) developed a gastrointestinal form. Among patients with gastrointestinal involvement, 33 patients (89%) had stage 2-4 gastrointestinal graft vs host disease. In univariable analysis, low level of citrulline associated with higher cumulative incidence of stage 2-4 gastrointestinal graft vs host disease, non-relapse mortality, and shorter overall survival. In multivariable analysis, low level of citrulline was the only risk factor independently associated with stage 2-4 gastrointestinal graft vs host disease (hazard ratio, 3.06; 95% CI, 1.37-6.85; P = .007); it also associated with increased non-relapse mortality (hazard ratio, 2.29; 95% CI, 1.24-4.22; P = .008). CONCLUSIONS: In a retrospective study with 191 patients, we associated a low plasma level of citrulline before allogeneic hematopoietic cell transplantation with a higher risk for stage 2-4 gastrointestinal graft vs host disease and non-relapse mortality. This marker might be used to manage patients before allogeneic hematopoietic cell transplantation.