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 < 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 < 0.0015). Leucine plasma appearance was 1.20 ± 0.15 μmol/ kg/min before treatment, it increased slightly and transiently after cyclophosphamide, and increased again from day 5 to day 7 after BMT (p < 0.01), suggesting increased protein breakdown. Leucine oxidation increased from 0.27 ± 0.07 before therapy to 0.97 ± 0.16 μmol/kg/min (p < 0.02) after cyclophosphamide and BMT. Nonoxidative leucine disappearance rate decreased slightly from 0.92 ± 0.08 to 0.75 ± 0.16 μmol/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 < 0.02) after cytoreductive therapy. After BMT it increased again to 9.9 ± 1.5 ml/kg/min (p < 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. Leucine incorporation into proteins (protein synthesis) was not altered inspite of an increase in plasma leucine concentration. ( Journal of Parenteral and Enteral Nutrition 14:480-484, 1990)