1. The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation
- Author
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Xiang Zhu, Taylor Moatz, Susan L. Furth, Adam Lane, Kelly E. Lake, Sonata Jodele, Jason T. Blackard, Bridget Litts, Benjamin L. Laskin, Alix E. Seif, Carolyn Lutzko, Stella M. Davies, Christopher E. Dandoy, Steve Kleiboeker, Timothy S. Olson, Nancy Bunin, Michelle R. Denburg, Michelle Altrich, Gregory Wallace, and Alexandra Duell
- Subjects
Microbiology (medical) ,medicine.medical_treatment ,Viremia ,Hematopoietic stem cell transplantation ,030230 surgery ,medicine.disease_cause ,Asymptomatic ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Child ,Polyomavirus Infections ,business.industry ,Hematopoietic Stem Cell Transplantation ,Immunity ,virus diseases ,medicine.disease ,BK virus ,Transplantation ,Major Articles and Commentaries ,Infectious Diseases ,chemistry ,BK Virus ,030220 oncology & carcinogenesis ,Immunology ,medicine.symptom ,business ,Stem Cell Transplantation ,Hemorrhagic cystitis ,Cidofovir ,Kidney disease - Abstract
Background BK polyomavirus (BKPyV) is associated with symptomatic hemorrhagic cystitis after hematopoietic cell transplantation (HCT). Little is known about the host immune response, effectiveness of antiviral treatment, or impact of asymptomatic replication on long-term kidney function. Methods In children and young adults undergoing allogeneic HCT, we quantified BKPyV viruria and viremia (pre-HCT and at Months 1–4, 8, 12, and 24 post-HCT) and tested associations of peak viremia ≥10 000 or viruria ≥109 copies/mL with estimated kidney function (glomerular filtration rate, eGFR) and overall survival at 2 years posttransplant. We examined the factors associated with viral clearance by Month 4, including BKPyV-specific T cells by enzyme-linked immune absorbent spot at Month 3 and cidofovir use. Results We prospectively enrolled 193 participants (median age 10 years) and found that 18% had viremia ≥10 000 copies/mL and 45% had viruria ≥109 copies/mL in the first 3 months post-HCT. Among the 147 participants without cystitis (asymptomatic), 58 (40%) had any viremia. In the entire cohort and asymptomatic subset, having viremia ≥10 000 copies/mL was associated with a lower creatinine/cystatin C eGFR at 2 years post-HCT. Viremia ≥10 000 copies/mL was associated with a higher risk of death (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1–4.2). Clearing viremia was associated with detectable BKPyV-specific T cells and having viremia Conclusions Screening for BKPyV viremia after HCT identifies asymptomatic patients at risk for kidney disease and reduced survival. These data suggest potential changes to clinical practice, including prospective monitoring for BKPyV viremia to test virus-specific T cells to prevent or treat BKPyV replication.
- Published
- 2019