Anat Stern1,2, Carolyn D Alonso3, Carolina Garcia-Vidal4, Celia Cardozo4, Monica Slavin5, Michelle K Yong5, Su Ann Ho5, Seema Mehta Steinke6, Robin K Avery6, Philipp Koehler7,8, Christof Scheid7, Oliver A Cornely7,8,9,10, Johan Maertens11, Yasmine Abi Aad12, David J Epstein13, Genovefa A Papanicolaou1, Dionysios Neofytos12. 1. Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel. 3. Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, USA. 4. Division of Infectious Diseases, Hospital Clinic, Barcelona, Spain. 5. Department of Infectious Disease and the National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia. 6. Division of Infectious Diseases, Johns Hopkins University, School of Medicine, Baltimore, USA. 7. Faculty of Medicine and University Hospital Cologne, Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Excellence Center for Medical Mycology (ECMM), University of Cologne, Cologne, Germany. 8. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. 9. Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany. 10. German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. 11. Department of Hematology, Leuven, Belgium. 12. Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland. 13. Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
Abstract
OBJECTIVES: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). METHODS: This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). RESULTS: We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P < 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL; P = 0.007) and 4 weeks (0.96 ± 0.89 mg/dL; P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P < 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. CONCLUSIONS: One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
OBJECTIVES: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). METHODS: This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). RESULTS: We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P < 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL; P = 0.007) and 4 weeks (0.96 ± 0.89 mg/dL; P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P < 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. CONCLUSIONS: One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
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