Cyclosporine metabolite pattern in blood from patients with acute GVHD after BMT
Christians, U.; Spiekermann, K.; Bader, A.; Schottmann, R.; Linck, A.; Wonigeit, K.; Sewing, K.F.; Link, H.
Bone Marrow Transplantation 12(1): 27-33
1993
ISSN/ISBN: 0268-3369 PMID: 8374534 Document Number: 408046
The cyclosporine (CYA) metabolite patterns in blood were evaluated in patients with liver dysfunction after allogeneic BMT. Fifty-five BMT patients were included in the study until discharge from hospital. Blood trough levels of CYA and 12 of its metabolites were quantified using HPLC. The patients were assigned to three groups: Group I (no acute GVHD, n = 23), group II (acute GVHD of the skin and good liver function, overall acute (GVHD: Grade I: n = 18, grade II: n = 2) and group III (aute GVHD nd liver dysfunction, overall acute GVHD: Grade II: n = 2, grade III/IV: n = 8). Analysis of the trough blood concentrations of CYA and its metabolites revealed higher concentrations of metabolite AM19 in group III than in the other groups without reaching statistical significance. During acute GVHD of the liver, the metabolites AM19 (p lt 0.01), AM1c9 (p lt 0.05) and AM1A (p lt 0.05) were significantly elevated compared with patients with normal liver function while CYA and all other metabolites did not differ. The CYA metabolite pattern in patients with acute GVHD and liver involvement was identical with that of liver graft patients during acute graft rejection, while the metabolite patterns of the patients without acute GVHD paralleled that of kidney grafted patients with normal liver function. Acute GVHD of the liver leads to an impaired elimination of CYA with increased blood concentrations of single CYA metabolites. Since it is not yet clear whether CYA metabolites are associated with the adverse effects of CYA, the metabolite pattern should be monitored in patients with acute GVHD of the liver and bilirubin concentrations in serum of gt 34 mu-mol/l.