BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation.

2023

04/2023

1537-6613

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.

10.1093/infdis/jiad117

J Infect Dis

37165301

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

2022

08/2022

1592-8721

10.3324/haematol.2022.280788

Haematologica

35979718

Psychometric Evaluation of the Brief RCOPE and Relationships with Psychological Functioning among Caregivers of Children Undergoing Hematopoietic Stem Cell Transplant.

2021

2021 Apr 16

1099-1611

<p><strong>OBJECTIVE: </strong>Spiritual and religious (S/R) coping is a relevant yet understudied domain of coping among caregivers of children undergoing hematopoietic stem cell transplantation (HCT). The aims of this manuscript are to: 1) conduct the first psychometric evaluation of the Brief RCOPE in this population; 2) examine levels of and changes in S/R coping over time; and 3) explore the relationship between S/R coping trajectories and psychological functioning post-HCT.</p>

<p><strong>METHODS: </strong>Caregivers (n=170) of children (ages ≤12 years, n=170) undergoing HCT completed the Brief RCOPE and the Brief Symptom Inventory (BSI) pre- and at multiple time points post-HCT discharge. Factor structure, internal consistency, and validity were examined. Growth mixture models were used to identify subgroups with similar S/R coping trajectories, with group memberships added to mixture models to explore relationships between group membership and caregiver psychological functioning trajectories.</p>

<p><strong>RESULTS: </strong>The Brief RCOPE exhibited the previously-supported two factor structure and each subscale demonstrated strong internal consistency (α=.85 and .92). Validity was supported by significant correlations with BSI scores. There were distinct subgroups of caregivers with different patterns of positive (n=4 subgroups) and negative (n=3 subgroups) S/R coping, with negative coping subgroup membership predicting changes in psychological functioning.</p>

<p><strong>CONCLUSIONS: </strong>The Brief RCOPE is a promising measure for assessing S/R coping among caregivers of children undergoing HCT and has the potential to identify caregivers at risk for poorer long-term psychological functioning. This article is protected by copyright. All rights reserved.</p>

10.1002/pon.5705

Psychooncology

33864325

Acute kidney injury in children after hematopoietic cell transplantation is associated with elevated urine CXCL10 and CXCL9.

2020

2020 Mar 09

1523-6536

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic (HCT) provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS: </strong>Children (&gt;2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at two large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value which was recorded ±1 day from when the research urine sample was obtained, as compared to the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI).</p>

<p><strong>RESULTS: </strong>A total of 176 patients were included from two pediatric centers. Thirty-six subjects from one center were analyzed as a discovery cohort and the remaining 140 subjects from the second center were analyzed as a validation cohort. AKI rates were 18-35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (p&lt;0.01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-gamma and interferon-alpha. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding.</p>

<p><strong>CONCLUSIONS: </strong>CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population.</p>

10.1016/j.bbmt.2020.02.024

Biol. Blood Marrow Transplant.

32165324

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

2019

2019 Dec 18

1537-6591

<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>

10.1093/cid/ciz1194

Clin. Infect. Dis.

31851312