期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 25, 期 5, 页码 1022-1030出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2019.01.012
关键词
Cytomegalovirus DNAemia; Cytomegalovirus infection; Cytomegalovirus disease; Preemptive antiviral therapy; Sirolimus; Mechanistic target of rapamycin inhibitor; Allogeneic hematopoietic stem cells transplantation; Quantitative PCR; Sirolimus exposure; Time-to-event analysis; PK/PD
资金
- Institute de Salud Carlos III [FIS16/01433]
- PERIS 2018-2020 from Generalitat de Catalunya [BDNS357800]
The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were allografted from an unrelated donor, and the donor CMV-serostatus was negative in 51 cases (31%). Fifty-six recipients (34%) developed CMV DNAemia necessitating preemptive therapy, with a cumulative incidence of 36% at a median follow-up of 25 months. Time to CMV DNAemia necessitating preemptive therapy was best described using a Gompertz function. CMV DNAemia necessitating preemptive therapy-predicting factors were antithymocyte globulin-based conditioning regimen (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1 to 4.1; P < .01) and sirolimus concentration (HR,.94; 95% CI, .87 to .99; P < .01). The risk of CMV DNAemia-RAT decreased by 6% for each 1 ng/mL increase in sirolimus trough concentration. In conclusion, we provide evidence on the association between sirolimus blood concentration and incidence of CMV DNAemia necessitating preemptive therapy in allo-HSCT recipients. Moreover, this study presents the first predictive model describing the time to CMV DNAemia necessitating preemptive antiviral therapy as a function of sirolimus drug concentration. (C) 2019 American Society for Blood and Marrow Transplantation.
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