First name
Jason
Middle name
T
Last name
Blackard

Title

BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation.

Year of Publication

2023

Date Published

04/2023

ISSN Number

1537-6613

Abstract

BK polyomavirus (BKPyV) infection is common after hematopoietic stem cell transplantation (HSCT) and is associated with the development of hemorrhagic cystitis (HC). The role that BKPyV plays in the pathogenesis of HC is not well characterized. We investigated the impact of BKPyV diversity on the development of HC using a previously established cohort of pediatric HSCT patients. There were 147 urine samples with quantifiable BKPyV at month 1 after HSCT; 137 (93.2%) were amplified using our in-house polymerase chain reaction approach and sent for next-generation sequencing. Subtype Ia was most frequent (61.3%), followed by subtype Ib1 (31.4%). The median viral load of subtype Ia samples was higher than for subtype Ib1 at month 1. Across the protein coding regions, APOBEC-induced mutations and signature patterns associated with HC were identified. This is the largest sequencing study of a single cohort of HSCT patients, providing a vast resource of sequence data for future analyses.

DOI

10.1093/infdis/jiad117

Alternate Title

J Infect Dis

PMID

37165301
Featured Publication
No

Title

Circulating endothelial cells and the study of vascular injury in children undergoing hematopoietic stem cell transplant.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1592-8721

DOI

10.3324/haematol.2022.280788

Alternate Title

Haematologica

PMID

35979718

Title

The natural history of BK polyomavirus and the host immune response after stem cell transplantation.

Year of Publication

2019

Date Published

2019 Dec 18

ISSN Number

1537-6591

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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 (eGFR) and overall survival for two years post-transplant. We examined factors associated with viral clearance by month 4 including BKPyV-specific T cells by enzyme-linked immune absorbent spot (ELISPOT) at month 3 and cidofovir use.</p>

<p><strong>RESULTS: </strong>We prospectively enrolled 193 participants (median age 10 years). 18% had viremia ≥10 000 copies/mL, and 45% had viruria ≥109 copies/mL in the first three months post-HCT. Among the 147 participants without cystitis (asymptomatic), 58 (40%) had any viremia. In the entire cohort and asymptomatic subset, viremia ≥10 000 copies/mL was associated with a lower creatinine/cystatin C eGFR two 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 viremia &lt;10 000 copies/mL, but not cidofovir exposure.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1093/cid/ciz1194

Alternate Title

Clin. Infect. Dis.

PMID

31851312

WATCH THIS PAGE

Subscription is not available for this page.