Impact of Preemptive Therapy for Cytomegalovirus on Toxicities after Allogeneic Hematopoietic Cell Transplantation in Clinical Practice: A Retrospective Single-Center Cohort Study

• Published in: Biology of blood and marrow transplantation 2020-08, Vol.26 (8), p.1482-1491
• Main Authors: Zavras, Phaedon, Su, Yiqi, Fang, Jiaqi, Stern, Anat, Gupta, Nitasha, Tang, Yuexin, Raval, Amit, Giralt, Sergio, Perales, Miguel Angel, Jakubowski, Ann A., Papanicolaou, Genovefa A.
• Format: Article
• Language: English
• Subjects: Acute kidney injury (AKI); Cytomegalovirus (CMV); Foscarnet; Ganciclovir; Hematopoietic cell transplantation (HCT); Neutropenia; Preemptive therapy (PET); Treatment-related toxicity; Valganciclovir
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2020.03.019

•We assessed toxicities by day 100 associated with preemptive therapy (PET) in a cohort of cytomegalovirus-seropositive hematopoietic cell transplantation recipients.•Neutropenia occurred in 41.8% of PET versus 28.6% of no PET patients (P = .0009).•Acute kidney injury (AKI) occurred in 10.2% of PET versus 7.8% of no PET patients (P = .19).•In multivariate models, PET increased the risk of neutropenia and AKI by 1.8- and 2.8-fold, respectively. (Val)ganciclovir (vGCV) or foscarnet (FCN) as preemptive therapy (PET) for cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) is associated with myelosuppression and nephrotoxicity, respectively. We analyzed a cohort of CMV-seropositive (R+) HCT recipients managed preemptively at a single center. The objectives of our study were to (1) quantify the frequencies of neutropenia and acute kidney injury (AKI) through day +100 (D100) post-HCT and at PET discontinuation and (2) assess the impact of PET on neutropenia and AKI in multivariate models. This was a retrospective cohort study of adult CMV R+ recipients who underwent allo-HCT at Memorial Sloan Kettering Cancer Center from March 18, 2013, through December 31, 2017, and were managed with PET. Patients were grouped by receipt of PET (PET and no PET). Neutropenia and AKI were defined by Common Terminology Criteria for Adverse Events version 4. Frequencies of toxicities by D100 were compared between relevant groups. The impact of PET on toxicities was examined in univariate and multivariate Poisson/negative binomial regression models. Of 368 CMV R+ HCT recipients, 208 (56.5%) received PET. Neutropenia by D100 occurred in 41.8% and 28.6% patients in PET and no PET, respectively (P = .0009). PET increased the risk of neutropenia (adjusted relative risk = 1.81; 95% confidence interval [CI], 1.48 to 2.21; P < .0001) in multivariate analyses. AKI by D100 occurred in 12.0% and 7.8% patients in PET and no PET, respectively (P = .19). PET increased the risk of AKI by 2.75-fold (95% CI, 1.71 to 4.42; P < .0001). When PET recipients were grouped by first antiviral, neutropenia by D100 occurred in 34.8% and 48.9% of vGCV and FCN recipients, respectively, (P = .08), and AKI occurred in 13.0% and 34.0% of vGCV and FCN recipients, respectively (P = .001). At discontinuation of vGCV or FCN, neutropenia was present in 11.2% versus 2.1% patients, respectively (P = .08), and AKI was present in 1.9% of versus 12.8% patients respectively (P = .005). Preemptive