1. Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
- Author
-
Juan Carlos Hernández-Boluda, Nuria Rabella, Laura Fox, Estela Giménez, Alejandro Pérez-Pitarch, Rafael Ferriols-Lisart, David Navarro, Pere Barba, Beatriz Guglieri-López, José Luis Piñana, Irene García-Cadenas, Jorge Sierra, Carlos Solano, David Valcárcel, Albert Esquirol, and Rodrigo Martino
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Premedication ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Hematopoietic stem cell transplantation ,Antiviral Agents ,Allogeneic hematopoietic stem cells transplantation ,Mechanistic target of rapamycin inhibitor ,Quantitative PCR ,03 medical and health sciences ,0302 clinical medicine ,Time-to-event analysis ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Cumulative incidence ,Cytomegalovirus disease ,Survival analysis ,Retrospective Studies ,Sirolimus ,Transplantation ,Dose-Response Relationship, Drug ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,PK/PD ,virus diseases ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Cytomegalovirus infection ,surgical procedures, operative ,Cytomegalovirus DNAemia ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Preemptive antiviral therapy ,Sirolimus exposure ,Female ,business ,Serostatus ,Immunosuppressive Agents ,030215 immunology ,medicine.drug - Abstract
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.
- Published
- 2019