Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation

Abstract

Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 ؋ 10 12 versus 5.7 ؋ 10 7 genome copies/d, P < .001) and larger total amounts of BKV excreted during BMT (4.9 ؋ 10 13 versus 7.7 ؋ 10 8 genome copies, P < .001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT. (Blood. 2001;98:1971-1978

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

“…1 Post-engraftment HC is strongly associated with BKV, although the role of BKV in its pathogenesis has not yet been fully elucidated. 1,3,7,8,10,11,23,24,[29][30][31][32] In this study, BKV viruria was detected in 83.7% among patients who had urine PCR BKV testing in the presence of a diagnosis of HC. This is comparable to previously published rates of post-engraftment BKV viruria ranging from 79 to 100%.…”

“…29,[33][34][35] With the advent of quantitative BKV PCR techniques, BKV load in the urine was quantitatively related to the occurrence of HC. 11, 29 Leung et al 11 demonstrated that HC patients had approximately 10 5 times higher peak viruria and total viral excretion than non-HC patients. The present study also showed that there was a significant difference in the viral load between the patients with asymptomatic viruria and symptomatic patients with BK-HC.…”

“…[1][2][3][4][5][6] While early-onset HC is usually mild with microscopic hematuria and secondary to the chemoradiation (e.g., CY), more severe HC with gross hematuria develops in the later course of allo-HSCT (⩾30 days after transplant) and is strongly associated with BK virus. 1,3,[7][8][9][10][11][12] Polyomavirus BK (BKV) is a double-stranded non-enveloped DNA virus first isolated from a urine sample obtained from a renal transplant recipient. [13][14][15] Primary infection occurs in childhood and remains in a latent phase most commonly in the kidney.…”

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

“…Transient BK viruria occurs in all allo-HSCT patients 19 with 4-25% of the patients developing sustained BKV-HC. 8,15,17,19,20,[26][27][28][29] A peak in BK viruria X3 to 6-log correlates with the occurrence of HC. 1,18,29,30 Consistent with these data, all the patients in our study had a BK viruria higher than 10 8 copies/mL indicating that BK viruria may not be the most relevant factor for the prediction of BKV-HC severity.…”

“…8,17,18 About 5-40% of the patients subsequently develop active HC. 13,19 HC is graded according to a literaturebased consensus definition: 17 Grades 1 and 2 correspond to the presence of microscopic and macroscopic hematuria, respectively; Grades 3 and 4 imply clots and severe bladder hemorrhage with renal impairment, respectively. Several studies have provided a better understanding of post-engraftment BKV-HC pathogenesis, suggesting a dual chronological process.…”