BK POLYOMAVIRUS AS THE CAUSE OF HEMORRHAGIC CYSTITIS IN PATIENTS TREATED WITH ALLOGENEIC STEM CELL TRANSPLANTATION

  • Stefan Stankovic Medical doctor
  • Irena Đunić
Keywords: allogeneic HSCT, BK polyomavirus, hemorrhagic cystitis

Abstract


Introduction: BK polyomavirus is a double-stranded DNA virus from the Polyomaviridae family. According to DNA sequences, this virus can be classified into six genotypes. In hematological patients enrolled in allogeneic hematopoietic stem cell transplantation (HSCT) programs, it can lead to hemorrhagic cystitis.

Aim: The aim of this study is calculating the prevalence of BK polyomavirus PCR (polymerase chain reaction) positivity in the blood and urine of patients involved in allogeneic HSCT, determining the predictive factors for clinical presentation of BK polyomavirus-associated hemorrhagic cystitis, as well as determining its effects on overall survival (OS) of the patients.

Materials and methods: This retrospective cohort study enrolled 42 patients from the Clinic of Hematology of the University Clinical Center of Serbia. The presence of the virus in blood and urine was determined by the PCR method. The survival rate of the patients in relation to hemorrhagic cystitis was calculated with the Kaplan-Meier method and comparison was performed with the log-rank test.

Results: A positive PCR result in the blood was found in 97.6% of the subjects, while urine tested positive in 100% of patients. The estimated survival time in patients without hemorrhagic cystitis was 44.357 months, while the group with the clinical presentation of hemorrhagic cystitis had an estimated survival time of 17.395 months. Based on the log-rank test, we found a significant difference in survival between those groups of patients (p = 0.049). With regards to leukocyte engraftment day, patients engrafted after D+14, had a higher frequency of hemorrhagic cystitis (p = 0.037).

Conclusion: BK polyomavirus-associated hemorrhagic cystitis is a common complication of treatment in patients suffering from hematological malignancies who are enrolled in an alo-HSCT program, and has a significant impact on OS.

References

Takasaka T, Goya N, Tokumoto T, Tanabe K, Toma H, Ogawa Y, et al. Subtypes of BK virus prevalent in Japan and variation in their transcriptional control region. J Gen Virol. 2004 Oct;85(Pt 10):2821-2827. doi: 10.1099/vir.0.80363-0.

Mackenzie EF, Poulding JM, Harrison PR, Amer B. Human polyoma virus (HPV)--a significant pathogen in renal transplantation. Proc Eur Dial Transplant Assoc. 1978;15:352-60.

Barber CE, Hewlett TJ, Geldenhuys L, Kiberd BA, Acott PD, Hatchette TF. BK virus nephropathy in a heart transplant recipient: case report and review of the literature. Transpl Infect Dis. 2006 Jun;8(2):113-21. doi: 10.1111/j.1399-3062.2006.00163.x.

Loeches B, Valerio M, Pérez M, Bañares R, Ledesma J, Fogeda M, et al; BKV Study Group of the Gregorio Marañón Hospital. BK virus in liver transplant recipients: a prospective study. Transplant Proc. 2009 Apr;41(3):1033-7. doi: 10.1016/j.transproceed.2009.02.021.

Muñoz P, Fogeda M, Bouza E, Verde E, Palomo J, Bañares R; BKV Study Group. Prevalence of BK virus replication among recipients of solid organ transplants. Clin Infect Dis. 2005 Dec 15;41(12):1720-5. doi: 10.1086/498118. Epub 2005 Nov 10.

Lee Y, Kim YJ, Cho H. BK virus nephropathy and multiorgan involvement in a child with heart transplantation . Clin Nephrol. 2019 Feb;91(2):107-113. doi: 10.5414/CN109520.

Gilis L, Morisset S, Billaud G, Ducastelle-Leprêtre S, Labussière-Wallet H, Nicolini FE, et al; Lyon BK virus Study group. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2014 May;49(5):664-70. doi: 10.1038/bmt.2013.235.

Leung AY, Suen CK, Lie AK, Liang RH, Yuen KY, Kwong YL. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Blood. 2001 Sep 15;98(6):1971-8. doi: 10.1182/blood.v98.6.1971.

Atilla E, Ateş C, Uslu A, Ataca Atilla P, Dolapçı I, Tekeli A, Topçuoğlu P. Prospective Analysis of Hemorrhagic Cystitis and BK Viremia in Allogeneic Hematopoietic Stem Cell Transplantation. Turk J Haematol. 2020 Aug 28;37(3):186-192. doi: 10.4274/tjh.galenos.2019.2019.0296.

Wu HL, Weber WC, Shriver-Munsch C, Swanson T, Northrup M, Price H, et al. Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications. Xenotransplantation. 2020 Jul;27(4):e12578. doi: 10.1111/xen.12578.

Laskin BL, Denburg MR, Furth SL, Moatz T, Altrich M, Kleiboeker S, et al. The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation. Clin Infect Dis. 2020 Dec 15;71(12):3044-3054. doi: 10.1093/cid/ciz1194.

Kerbauy LN, Kerbauy MN, Bautzer V, Chapchap EC, de Mattos VRP, da Rocha JDA, et al. Severe hemorrhagic cystitis caused by the BK polyomavirus is associated with decreased survival post-allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2019 Oct;21(5):e13101. doi: 10.1111/tid.13101.

Published
2022/09/26
Section
Original articles