20 BK Virus Subtype III Is Associated with Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Track: BMT Tandem "Scientific" Meeting
Thursday, February 14, 2013, 4:45 PM-6:15 PM
Ballroom A-D (Salt Palace Convention Center)
Koji Kato , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Toshihiro Miyamoto , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Yoshitaka Eto , Center for the study of global infection, Kyushu University Hospital, Japan
Koji Yonemoto , Biostatistics, Kurume University, Japan
Shuro Yoshida , Department of Hematology, Hamanomachi Hospital, Japan
Noriyuki Saito , Department of Hematology, Hamanomachi Hospital, Japan
Hideho Henzan , Department of Hematology, Hamanomachi Hospital, Japan
Yoshikiyo Ito , Department of Hematology, Harasanshin Hospital, Japan
Junichiro Yuda , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Masayasu Hayashi , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Shuichiro Takashima , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Shingo Urata , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Yoshikane Kikushige , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Seido Oku , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Takuro Kuriyama , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Yasuo Mori , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Tsuyoshi Muta , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Katsuto Takenaka , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan
Hiromi Iwasaki , Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Japan
Tomohiko Kamimura , Department of Hematology, Harasanshin Hospital, Japan
Tetsuya Eto , Department of Hematology, Hamanomachi Hospital, Japan
Takanori Teshima , Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Japan
Nobuyuki Shimono , Center for the study of global infection, Kyushu University Hospital, Japan
Jun Hayashi , Center for the study of global infection, Kyushu University Hospital, Japan
Koichi Akashi , Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Japan

[Background] BK virus (BKV) associated hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been increasingly reported. However, there is less information about diagnosis and treatment. The purpose of this study is to clarify the significance of viral subtypes in the pathogenesis of BKV-HC in Japanese subjects.

[Methods] Urinary decoy cells compatible with BKV reactivation were examined in patients every week as post-HSCT screening. The real-time quantitative PCR (qPCR) for BKV and adenovirus (ADV) were performed on urine samples when patients developed HC and/or had positive decoy cells. BKV subtypes (I-IV) were determined through viral DNA sequencing in each patients with positive BKV qPCR (>2x102 copies/ml).

[Results] A total of 84 allo-HSCTs were performed between July 2010 and April 2012(Fig). Of the 31 patients (pts) whom only BKV reactivation was detected, 11 developed HC. BKV subtypes were determined in these 31 pts (Ia: n=2, Ib-1: n=2, Ic: n=16, III: n=8, and IVb-1: n=3). Interestingly, BKV subtype III was found in 6 of 11 pts with BKV-HC. There was no direct correlation between development of HC and viral load (HC vs No-HC: 1.3 vs 2.0x107 copies/mL, p=0.86). In addition, there was no significant association between HC and other risk factors such as age (p=0.45), disease status (p=1.00), conditioning (p=0.71), donor source (p=0.43) and acute GVHD (p=0.71). Only BKV subtype III had a statistically significant correlation with HC (OR: 10.8, 95%CI: 1.64-70.93, p=0.013).

[Conclusion] BKV is ubiquitous among humans, infecting children asymptomatically and then persisting in renal tissue. Subtype Ic is most prevalent (>90%), followed by subtype IV, while subtype III are rarely found in Japan. Our data suggested the importance of BKV subtype III in the development of BKV-HC. Further studies focused on the viral genomic variation in the pathogenesis of BKV-HC are warranted.

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