Management of BK Virus-Associated Hemorrhagic Cystitis in Pediatric Malignancies

1. BK virus-associated hemorrhagic cystitis in children suffering malignancies:The report of three cases Dr. Shahla Ansari Professor of pediatric hematology and oncology. Ali-Asghar hospital Dr. Neda Ashayeri Fellow of pediatric hematology and oncology

2. Introduction • BK virus: • One of the main members belonging to polyomaviruses • Associated with HC • Rarely reported in the literature especially among young children following chemotherapy • we describes our experience on three children with malignancy under treated with chemotherapy suffering HC due to BK virus infection

3. Case 1: • A 3-year-old boy • Burkittlymphoma undertreated with chemotherapy • Two months after starting chemotherapy • Hematuriaand dysuria along with mild feverappeared • Ultrasonography: bladder with thickened and irregular wall containing floating and vesicular echogenic pattern have raised the probability of cystitis.

4. Nephrology cosult • PCR for BK virus: Positive/ copy number:1.000.000. • Rx: ciprofloxacin and IVIG. • After three days: hematuria was disappeared. Ciprofloxacin was continued led to decrease dysuria but it was not completely resolved. • Ten days later: BK virus copy number reduced to 395245. • IVIG was prescribed again for him that led to completely disappearing the symptoms and thus chemotherapy continued. • Final molecular assessment of BK virus one month after positivity led to negative result.

5. Case 2 • A 5-year girl • ALL from 18 months of age that under treated with chemotherapy. • Dysuriaand hematuria between the sessions of chemotherapy. • PCR for BK virus: Positive • Rx: Leflunomide + chemotherapy was discontinued.

6. Due to the patient's critically ill condition and appearing fever, positivity of BK virus in blood was also checked : Positive • Leflunomidewas continued. • After one month, symptoms completely resolved. The BK virus was rechecked that was revealed to be negative.

7. Case 3 • A 7years girl • Astrocytomathat underwent surgery for her mass. After one year the mass relapsed and then radiotherapy and chemotherapy began for her. • During the chemotherapy dysuria and hematuria. • Urine analysis: many RBCs without bacteria. • PCR for BK virus: Positive • Rx: Leflunamideand IVIG. • Dysuria but sever hematuria continued. So we prescribed Aryoseven and after 3 days hematuria resolved. • One month later, all the symptoms completely resolved and we rechecked the BK virus in the urine that was revealed to be negative.

8. Discussion • BK virus: primarily isolated in 1971 • Clinically, in most cases infected by BK virus can be in latent form till the body undergoes immunosuppression status that can lead to severe ill condition in affected patients. • reactivation of latent BK infection: • rarely presenting as a clinical problem • in the renal tubular epithelial

9. The primary route of transmission remains unclear, with both respiratory and oral routes proposed • Main risk factor for nephropathy due to transplantation or immunosuppression • The clinical manifestations: non-specific symptoms of renal dysfunction or bladder inflammation such as raised creatinine, dysuria or hematuria • An abnormal urinalysis can reveal renal tubular cells and inflammatory cells

10. BK virus-associated HC: frequent in patients who undergoing bone marrow transplantation but it rarely occurs among other immunosuppressed patients particularly in those who are planned for chemotherapy due to hematopoietic malignancies • This is unfortunate because HC can deteriorate disease course leading poorer outcome, longer hospitalization, higher mortality and morbidity, and increased financial burden. • As shown in our cases, we can first show that BK virus-related HC can be appeared early after starting chemotherapy due to leukemia or lymphoma in young children.

11. A 15-year-young female /2011/ france • Severe hemorrhagic cystitis. • Hodgkin disease, with chemotherapy using COOP then OPPA • A 5-year-old boy/ 2013/ Iran • Standard-risk ALL with t(12,21) • Intermittent fever and hematuria at the end of the second year of maintenance chemotherapy. • Chemotherapy protocol as ALL-BFM-90 • BK Rx: IVIG/ ciprofloxacin • A 10-year-old boy/ 2013/ Canada • ALL

12. Early diagnosis: can successfully help to control HC and to prevent its adverse consequences. • As the first attempt: Immunosuppression first reduced leading successfully elimination of infection • IVIG and leflunomide as the second line approach to eliminate virus and HC relief leading successfully improvement of HC. • Leflunomidehas a powerful antiviral activity by inhibiting virus replication in urinary system. • The beneficial effects of IVIG for treating BK virus have been also shown

13. Conclusion • Early detection of BK virus using RT-PCR technique • Administration of antiviral agents especially IVIG or leflunomide • BK virus-related HC can be successfully managed in children affected by hematopoietic malignancies • Their treatment by chemotherapy can be even continued after virus elimination.

14. Thank you