Presentation of BK polyomavirus–associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation

Author:

Imlay Hannah123ORCID,Xie Hu1,Leisenring Wendy M.1ORCID,Duke Elizabeth R.12ORCID,Kimball Louise E.1,Huang Meei-Li1,Pergam Steven A.12ORCID,Hill Joshua A.12,Jerome Keith R.14,Milano Filippo12,Nichols W. Garrett5,Pang Phillip S.6,Hirsch Hans H.7,Limaye Ajit P.2,Boeckh Michael12

Affiliation:

1. Fred Hutchinson Cancer Research Center, Seattle, WA;

2. Department of Medicine, University of Washington, Seattle, WA;

3. Department of Medicine, University of Utah, Salt Lake City, UT;

4. Department of Laboratory Medicine, University of Washington, Seattle, WA;

5. Chimerix Inc., Durham, NC;

6. Vir Biotechnology Inc., San Francisco, CA; and

7. Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland

Abstract

Abstract BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.

Publisher

American Society of Hematology

Subject

Hematology

Reference53 articles.

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5. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients;Cesaro;J Antimicrob Chemother,2018

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