6533b7dcfe1ef96bd1271ee3

RESEARCH PRODUCT

Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Juan Carlos Hernández-boludaNuria RabellaLaura FoxEstela GiménezAlejandro Pérez-pitarchRafael Ferriols-lisartDavid NavarroPere BarbaBeatriz Guglieri-lópezJosé Luis PiñanaIrene García-cadenasJorge SierraCarlos SolanoDavid ValcárcelAlbert EsquirolRodrigo Martino

subject

AdultMaleOncologymedicine.medical_specialtyPremedicationmedicine.medical_treatmentCongenital cytomegalovirus infectionHematopoietic stem cell transplantationAntiviral AgentsAllogeneic hematopoietic stem cells transplantationMechanistic target of rapamycin inhibitorQuantitative PCR03 medical and health sciences0302 clinical medicineTime-to-event analysisInternal medicineHumansTransplantation HomologousMedicineCumulative incidenceCytomegalovirus diseaseSurvival analysisRetrospective StudiesSirolimusTransplantationDose-Response Relationship Drugbusiness.industryHazard ratioHematopoietic Stem Cell TransplantationPK/PDvirus diseasesRetrospective cohort studyHematologyMiddle Agedmedicine.diseaseCytomegalovirus infectionsurgical procedures operativeCytomegalovirus DNAemia030220 oncology & carcinogenesisSirolimusCytomegalovirus InfectionsPreemptive antiviral therapySirolimus exposureFemalebusinessSerostatusImmunosuppressive Agents030215 immunologymedicine.drug

description

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.

yearjournalcountryeditionlanguage
2019-01-01
https://www.fundanet.incliva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=2831