Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
Guglieri-Lopez, Beatriz (Hospital Universitari Doctor Peset (València))
Perez-Pitarch, Alejandro (Hospital Clínico Universitario de València)
Garcia Cadenas, Irene (Institut d'Investigació Biomèdica Sant Pau)
Gimenez, Estela (Hospital Clínico Universitario de València)
Barba, Pere (Hospital Universitari Vall d'Hebron)
Rabella, Núria (Institut d'Investigació Biomèdica Sant Pau)
Hernandez-Boluda, Juan Carlos (Hospital Clínico Universitario de València)
Fox, Maria Laura (Hospital Universitari Vall d'Hebron)
Valcárcel, David (Hospital Universitari Vall d'Hebron)
Esquirol, Albert (Institut d'Investigació Biomèdica Sant Pau)
Ferriols-Lisart, Rafael (Hospital Clínico Universitario de València)
Sierra, Jorge (Institut d'Investigació Biomèdica Sant Pau)
Solano, Carlos (Universitat de València)
Navarro, David (Universitat de València)
Martino Bofarull, Rodrigo (Institut d'Investigació Biomèdica Sant Pau)
Piñana, José Luis (Instituto de Salud Carlos III)
Universitat Autònoma de Barcelona

Date:	2019
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.
Grants:	Ministerio de Economía y Competitividad PI16/01433
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Allogeneic hematopoietic stem cells transplantation ; Cytomegalovirus DNAemia ; Cytomegalovirus disease ; Cytomegalovirus infection ; Mechanistic target of rapamycin inhibitor ; PK/PD ; Preemptive antiviral therapy ; Quantitative PCR ; Sirolimus ; Sirolimus exposure ; Time-to-event analysis
Published in:	Biology of blood and marrow transplantation, Vol. 25 Núm. 5 (may 2019) , p. 1022-1030, ISSN 1523-6536

DOI: 10.1016/j.bbmt.2019.01.012
PMID: 30639821

9 p, 1.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles