Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis.
A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrations, variability of concentrations, and failures to maintain target levels that distinguished patients with low, intermediate, and high risks of acute GVHD (hazard ratios (HR) 1.77, 95%CI 1.36-2.32, p < 0.0001). This model was used to compare 95 patients with CsA and 239 with Tac GVHD prophylaxis. In the multivariate analysis, incorporating PK risk, no differences were observed for grade II-IV acute GVHD (HR 0.73, 95%CI 0.48-1.10, p = 0.13), but grade III-IV acute GVHD was lower in the Tac group (HR 0.47, 95%CI 0.28-0.78, p = 0.004). The observed difference was due to patients with high PK risk (HR 0.377, 95%CI 0.19-0.75, p = 0.005), but not with low and intermediate PK risk (p > 0.05). Patients in the Tac group had better GVHD relapse-free survival (HR = 0.659, p = 0.01) and comparable overall survival (p > 0.05). In conclusion, PK risk should be accounted for in comparisons of GVHD prophylaxis regimens with calcineurin inhibitors, and Tac was superior to CsA in patients with high, but not intermediate and low PK risk.
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. moisiv@mail.ru.
Ivan Sergeevich
IS
Moiseev
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Ekaterina Andreevna
EA
Burmina
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Albert Radikovich
AR
Muslimov
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Olga Vladislavovna
OV
Pirogova
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Sergey Nikolaevich
SN
Bondarenko
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Elena Igorevna
EI
Darskaya
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Yuliya Alexandrovna
YA
Tarakanova
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Nadegda Georgievna
NG
Senina
R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia.
Boris Vladimirovich
BV
Afanasyev
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D016019:Survival Analysis; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D055815:Young Adult
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
Allogeneic stem cell transplantation; Cyclosporine A; Graft-versus-host disease; Pharmacokinetics; Tacrolimus