Protein Metabolism Assessed by 1–13C Leucine Infusions in Patients Undergoing Bone Marrow Transplantation

Abstract

Patients receiving cytoreductive therapy and bone marrow transplantation (BMT) are known to develop marked protein catabolism. To assess the contribution of whole body protein breakdown, amino acid oxidation and incorporation into proteins, plasma leucine kinetics (1-13C-leucine infusion technique) were determined in six patients five times within 14 days before and after cytoreductive therapy (Cyclophosphamide and total body irradiation) and marrow transplantation. Nitrogen balance became negative (-0.20 +/- 0.04 g/Kg/24 hr) after cyclophosphamide (p less than 0.01) and was -0.25 +/- 0.05 g/Kg/24 hr 7 days after BMT in spite of total parenteral nutrition. Plasma leucine concentration increased after BMT by 67% (p less than 0.0015). Leucine plasma appearance was 1.20 +/- 0.15 mumol/kg/min before treatment, it increased slightly and transiently after cyclophosphamide, and increased again from day 5 to day 7 after BMT (p less than 0.01), suggesting increased protein break-down. Leucine oxidation increased from 0.27 +/- 0.07 before therapy to 0.97 +/- 0.16 mumol/kg/min (p less than 0.02) after cyclophosphamide and BMT. Nonoxidative leucine disappearance rate decreased slightly from 0.92 +/- 0.08 to 0.75 +/- 0.16 mumol/kg/min after BMT (ns). Leucine metabolic clearance rate decreased from 11.8 +/- 1.65 before therapy to 6.9 +/- 0.70 ml/kg/min (p less than 0.02) after cytoreductive therapy. After BMT it increased again to 9.9 +/- 1.5 ml/kg/min (p less than 0.02). The results demonstrate that patients undergoing cytoreductive therapy and bone marrow transplantation develop negative nitrogen balance due to increased protein breakdown associated with increased leucine oxidation and increased metabolic clearance rate.(ABSTRACT TRUNCATED AT 250 WORDS)