BK Virus Infections in Pediatric Patients with Hematopoietic Stem Cell Transplantation

Abstract

Aim: BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication in patients after hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the incidence of BKV infection in pediatric patients receiving HSCT. Material and Methods: Total of 51 patients aged between 16 months and 16 years old and followed up between October 2015 and September 2017 were included in the study. The patients were monitored by quantitative real-time polymerase chain reaction (Anatolia Geneworks, Turkey) test for the detection of BKV DNA in urine and blood. Results: Of patients, 46 received allogeneic HSCT and 5 autologous HSCT. BKV DNA positivity was detected in urine and/or blood of total 27 (52.9%) patients in whom 26 (56.5%) of 46 patients with allogeneic transplantation, and 1 (20.0%) of 5 patients with autologous transplantation. BKV viral load in urine >107 copies/ml required for preemptive treatment was detected in 12 (26.1%) of 46 patients received allogeneic HSCT. The development of HC was prevented in 9 (75.0%) of the 12 patients given preemptive treatment, while 3 (25.0%) cases developed HC and cured by treatment. BKV viruria was detected >109 copies/ml in two weeks before the onset of HC and was accepted as a prognostic indicator for predictive diagnosis of HC. BKV viremia was found >104 copies/ml in 1 patient within two weeks before the onset of cystitis. Conclusion: Screening for BKV infection, especially BKV viruria in HSCT patients, is recommended for the predictive diagnosis of HC in patients at high risk.

Keywords

• BK virus
• hematopoietic stem cell transplantation
• haemorrhagic cystitis
• polymerase chain reaction

Hematopoetik Kök Hücre Transplantasyonu olan Pediatrik Hastalarda BK Virüs Enfeksiyonları

Abstract

Amaç: BK virus (BKV) ile ilişkili hemorajik sistit (HS), hematopoetik kök hücre transplantasyonu (HKHT) yapılan hastalarda yaygın görülen bir komplikasyondur. Bu çalışmanın amacı, HKHT yapılan çocuk hastalarda BKV enfeksiyonu insidansının araştırılmasıdır. Gereç ve Yöntemler: Çalışmaya Ekim 2015 ile Eylül 2017 tarihleri arasında izlenen, yaşları 16 ay ile 16 yıl arasında olan toplam 51 hasta dahil edilmiştir. Hastalar BKV DNA'nın idrar ve kanda tespiti için kantitatif gerçek-zamanlı polimeraz zincir reaksiyonu (Anaolia Geneworks, Türkiye) testiyle monitörize edilmiştir. Bulgular: Hastaların 46'sına allojenik HKHT ve 5'ine otolog HKHT yapılmıştır. Allojenik nakil yapılan 46 hastanın 26'sında (%56,5) ve otolog nakil yapılan 5 hastanın 1'inde (%20,0) olmak üzere toplam 27 (%52,9) hastanın idrar ve/veya kanında BKV DNA pozitifliği saptanmıştır. Allojenik HKHT yapılan 46 hastanın 12 (%26,1)'sinde preemptif tedavi için gereken idrarda >107 kopya/ml BKV viral yük düzeyi tespit edilmiştir. Preemptif tedavi uygulanan 12 hastanın 9'unda (%75,0) HS gelişmesi önlenirken 3'ünde (%25,0) HS gelişmiş ve tedaviyle iyileşmiştir. HS gelişmeden önceki iki hafta içinde BKV virurisi >109 kopya/ml olarak tespit edilmiş ve HS prediktif tanısı için prognostik bir gösterge olarak kabul edilmiştir. BKV viremisi 1 hastada sistit gelişmesinden önceki iki hafta içinde >104 kopya/ml olarak tespit edilmiştir. Sonuç: Yüksek riskli hastalarda HS prediktif tanısı için BKV enfeksiyonu, özellikle HKHT hastalarında BKV virüri taraması önerilir.

Keywords

• BK virus
• hematopoietik kök hücre transplantasyonu
• hemorajik sistit
• polimeraz zincir reaksiyonu

References

1. Cesaro S, Dalianis T, Hanssen Rinaldo C, Koskenvuo M, Pegoraro A, Einsele H, et al. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated hemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018;73(1):12-21.
2. Han SB, Cho B, Kang JN. BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation. Korean J Pediatr. 2014;57(12):514-9.
3. Erard V, Kim HW, Corey L, Limaye A, Huang ML, Myerson D, et al. BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients. Blood. 2005;106(3):1130-2.
4. O'Donnell PH, Swanson K, Josephson MA, Artz AS, Parsad SD, Ramaprasad C, et al. BK virus infection is associated with hematuria and renal impairment in recipients of allogeneic hematopoetic stem cell transplants. Biol Blood Marrow Transplant. 2009;15(9):1038-48.
5. Dalianis T, Ljungman P. Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients. Anticancer Res. 2011;31(3):939-44.
6. Berber I, Erkurt MA, Yetkin F, Kuku I, Kaya E, Bodakci E, et al. BK virus in allogeneic and autologous bone marrow transplantation: review article. American Journal of Medical Sciences and Medicine. 2014;2(5):85-8.
7. Hayden RT, Gu Z, Liu W, Lovins R, Kasow K, Woodard P, et al. Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2015;17(2):234-41.
8. de Padua Silva L, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95(7):1183-90.

9. Bogdanovic G, Priftakis P, Giraud G, Kuzniar M, Ferraldeschi R, Kokhaei P, et al. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation. J Clin Microbiol. 2004;42(11):5394-6.
10. Gorczynska E, Turkiewicz D, Rybka K, Toporski J, Kalwak K, Dyla A, et al. Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005;11(10):797-804.
11. Oshrine B, Bunin N, Li Y, Furth S, Laskin BL. Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19(12):1702-7.
12. Laskin BL, Denburg M, Furth S, Diorio D, Goebel J, Davies SM, et al. BK viremia precedes hemorrhagic cystitis in children undergoing allogeneic hematopoietic stemcell transplantation. Biol Blood Marrow Transplant. 2013;19(8):1175-82.
13. Giraud G, Priftakis P, Bogdanovic G, Remberger M, Dubrulle M, Hau A, et al. BK-viruria and hemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts. Bone Marrow Transplant. 2008;41(4):737-42.
14. Cesaro S, Tridello G, Pillon M, Calore E, Abate D, Tumino M, et al. A prospective study on the predictive value of plasma BK virus-DNA load for hemorrhagic cystitis in pediatric patients after stem cell transplantation. J Pediatric Infect Dis Soc. 2015;4(2):134-42.
15. Kwon HJ, Kang JH, Lee JW, Chung NG, Kim HK, Cho B. Treatment of BK virus-associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single-center experience. Transpl Infect Dis. 2013;15(6):569-74.
16. Giraud G, Bogdanovic G, Priftakis P, Remberger M, Svahn BM, Barkholt L, et al. The incidence of hemorrhagic cystitis and BK viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen. Haematologica. 2006;91(3):401-4.
17. Lee YJ, Zheng J, Kolitsopoulos Y, Chung D, Amigues I, Son T, et al. Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations. Biol Blood Marrow Transplant. 2014;20(8):1204-10.
18. Mori Y, Miyamoto T, Kato K, Kamezaki K, Kuriyama T, Oku S, et al. Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):458-65.
19. Park YH, Lim JH, Yi HG, Lee MH, Kim CS. BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: clinical characteristics and utility of leflunomide treatment. Turk J Hematol. 2016;33(3):223-30.
20. Pérez-Huertas P, Cueto-Sola M, Escobar-Cava P, Fernández-Navarro JM, Borrell-García C, Albert-Marí A, et al. BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in the pediatric population. J Pediatr Oncol Nurs. 2017;34(1):13-9.
21. Gilis L, Morisset S, Billaud G, Ducastelle-Leprêtre S, Labussière-Wallet H, Nicolini FE, et al. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2014;49(5):664-70.