Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia

摘要

Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein carbonyls and thiobarbituric acid reactive substances) were assessed in association with febrile neutropenia. The vitamin C status of the study participants decreased from 44 ± 7 μmol/L to 29 ± 5 μmol/L by week one ( p = 0.001) and 19 ± 6 μmol/L by week two ( p 0.001), by which time all of the participants had undergone a febrile episode. By week four, vitamin C status had increased to 37 ± 10 μmol/L ( p = 0.1). Pre-transplantation, the cohort comprised 19% with hypovitaminosis C (i.e., 23 μmol/L) and 8% with deficiency (i.e., 11 μmol/L). At week one, those with hypovitaminosis C had increased to 38%, and at week two, 72% had hypovitaminosis C, and 34% had outright deficiency. C-reactive protein concentrations increased from 3.5 ± 1.8 mg/L to 20 ± 11 mg/L at week one ( p = 0.002), and 119 ± 25 mg/L at week two ( p 0.001), corresponding to the development of febrile neutropenia in the patients. By week four, these values had dropped to 17 ± 8 mg/L ( p 0.001). There was a significant inverse correlation between C-reactive protein concentrations and vitamin C status ( r = ?0.424, p 0.001). Lipid oxidation (thiobarbituric acid reactive substances (TBARS)) increased significantly from 2.0 ± 0.3 μmol/L at baseline to 3.3 ± 0.6 μmol/L by week one ( p 0.001), and remained elevated at week two ( p = 0.003), returning to baseline concentrations by week four ( p = 0.3). Overall, the lowest mean vitamin C values (recorded at week two) corresponded with the highest mean C-reactive protein values and lowest mean neutrophil counts. Thus, depleted vitamin C status in the HSCT patients coincides with febrile neutropenia and elevated inflammation and oxidative stress.