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The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation
Benjamin L Laskin1,2, Michelle R Denburg1,2, Susan L Furth1,2
1Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Insights
BK polyomavirus (BKPyV) viremia after hematopoietic cell transplantation (HCT) is linked to reduced kidney function and survival. Monitoring BKPyV viremia and T-cell responses may improve patient outcomes.
Area of Science:
- Virology
- Immunology
- Transplantation Medicine
Background:
- BK polyomavirus (BKPyV) is a known cause of hemorrhagic cystitis post-hematopoietic cell transplantation (HCT).
- Limited understanding exists regarding host immune responses, antiviral efficacy, and the long-term renal impact of asymptomatic BKPyV replication.
- Investigating these factors is crucial for improving patient care after HCT.
Purpose of the Study:
- To quantify BKPyV viruria and viremia in pediatric and young adult HCT recipients.
- To assess the association between BKPyV viral load, kidney function (eGFR), and overall survival at two years post-HCT.
- To identify factors, including T-cell response and antiviral treatment, associated with viral clearance.
Main Methods:
- Prospective enrollment of 193 children and young adults undergoing allogeneic HCT.
- Quantification of BKPyV viruria and viremia at multiple time points pre- and post-HCT.
- Measurement of BKPyV-specific T cells and assessment of cidofovir use for viral clearance analysis.
Main Results:
- 45% of participants had significant viruria (≥10^9 copies/mL) and 18% had significant viremia (≥10,000 copies/mL) within 3 months post-HCT.
- High BKPyV viremia (≥10,000 copies/mL) was associated with lower eGFR and increased mortality risk (aHR 2.2) at 2 years.
- Viral clearance by Month 4 correlated with detectable BKPyV-specific T cells, not cidofovir treatment.
Conclusions:
- Screening for BKPyV viremia in HCT patients can identify those at risk for kidney disease and reduced survival.
- These findings support prospective BKPyV viremia monitoring and T-cell testing to guide prevention and treatment strategies.
- Potential clinical practice changes include proactive BKPyV monitoring to manage complications and improve long-term outcomes.
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 <10 000 copies/mL, but not cidofovir exposure.
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.
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