Human polyomavirus BK (BKV) load and haemorrhagic cystitis in bone marrow transplantation patients

Summary:We reviewed 242 allogeneic hematopoietic stem cell transplantation (HSCT) recipients retrospectively over a 2-year period (January 1998-December 1999 in order to analyze the characteristics and assess the outcomes of infectious complications in patients after HSCT in Korea. Bacteria were the major pathogens before engraftment, and viral and fungal infections predominated during the post-engraftment period. Varicella zoster virus was the most common viral pathogen after engraftment. Cytomegalovirus disease occurred mainly in the late-recovery phase. The frequency of mold infection was higher than that of yeast. There was a relatively high incidence of tuberculosis (3.0%) and Pneumocystis carinii pneumonia (6.5%). One case of death by measles confirmed by autopsy was also noted. Overall, cumulative mortality was 43% (104/242), and 59.6% of these deaths (62/104) were infection-related. Allogeneic HSCT recipents from unrelated donors were prone to infectious complication and higher mortality than those from matched sibling (17/39 (43.6%) vs 45/203 (22.2%), respectively; Po0.01; odd ratio 2.5; 95% confidence interval 1.2-5.1). As infection was the main post-HSCT complication in our data, more attention should be given to the management of infections in HSCT recipients.

Section: Discussionsupporting

confidence: 66%

Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea

Lee

Choi

et al. 2004

“…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%.…”

Section: Discussionmentioning

confidence: 57%

“…3,7,10,23 However, more than half of the patients remained asymptomatic with BKV viruria. 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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Uhm

Hamad

Michelis

et al. 2014

Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10 10 copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P = 0.003), CMV viremia (HR 1.88, P = 0.014) and aGVHD grade 3-4 (HR 1.71, P = 0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

“…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. As proposed by Bedi et al and others,17,23,31,32 BKV-HC is a threestep process, in which the last phase corresponds to hematopoietic reconstitution.…”

Section: High Burden Of Bk Virus-associated Hemorrhagic Cystitis L Gimentioning

confidence: 99%

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

Gilis

Morisset

Billaud

et al. 2014

118

149

on behalf of the Lyon BK virus Study group 5 BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P ¼ 0.028), unrelated donor (P ¼ 0.0178), stem cell source (P ¼ 0.0001), HLA mismatching (P ¼ 0.0022) and BU in conditioning regimen (P ¼ 0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P ¼ 0.0005) and peripheral blood stem cells (P ¼ 0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P ¼ 0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (Po0.0001), more RBC (P ¼ 0.0003) and platelet transfusions (Po0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at h2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.