BK Viruria in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: Increased Incidence in Patients Receiving Alemtuzumab (ALEM) as Conditioning Therapy and Lack of Efficacy of Cidofovir.

BK virus is a highly ubiquitous polyoma virus with a peak seroprevalence in childhood ranging from 60–100%. After primary infection, which is often asymptomatic or occasionally associated with fever and upper respiratory symptoms, the virus remains latent in the kidneys. During heavy immunosuppression, as occurs following agents such as Alem or anti-thymocyte globulin (ATG), the virus reactivates and can cause significant uroepithelial cell lysis with resultant hemorrhagic cystitis (HC). Between April 2003 and June 2004, 25 patients (15 males, 10 females) undergoing allogeneic (13 MSD, 12 VUD) hematopoietic stem cell transplantation for a variety of indications (18 MDS/AML, 3 NHL, 1 CLL, 2 MM, 1 CML) were found to have BK viruria. Patients ranged in age from 20–67 years. 16 patients underwent ablative conditioning (12 busulfex [Bu]-fludarabine [Flu]-Alem, 1 Bu-Flu-ATG, 2 total body irradiation (TBI)-cyclophosphamide (Cy), 1 TBI-etoposide) whereas 9 patients underwent reduced-intensity (RI) conditioning (5 Blu-Flu-Alem, 2 Bu-Flu-ATG, 1 Flu-Cy, 1 Cy-ATG). Patients treated on ablative regimens containing Bu received a total dose of 12.8 mg/kg whereas those treated with RI conditioning received 6.4 mg/kg. Those who received Flu got 30 mg/m²/d for 5 doses. Alem-based regimens contained 30 mg/d for 3 days or 20 mg/d for 5 days. Graft-versus-host disease (GVHD) prophylaxis consisted of: tacrolimus (FK) alone (n=16), FK + methotrexate (MTX) (n=7), FK + steroids (n=1), cyclosporine-MTX (n=1). 23 patients had BK viral loads in urine measured by PCR with peak levels ranging from 1500 copies/ml to > 200,000,000 copies/ml. BK virus was first detected in the urine anywhere from day −7 to day +85 post-transplant. The time to peak level of BK viruria ranged from day −2 to day + 85 (median 17 days). 40 % (10/25) of these BK viruric patients developed symptomatic HC and 16 % (4/25) developed uretostenosis and/or hydronephrosis (2 required ureteral stent placement). Only 1 of 14 patients treated with multiple doses of Cidofovir (range 3–26 doses) either cleared their viruria by qualitative assay or had greater than a 3 log reduction by quantitative PCR within 4 weeks of starting antiviral therapy; 2 of the 13 patients did have a 2 log reduction in viral load within 4 weeks of initiation of antiviral therapy. It is interesting that 27% (3/11) of patients not treated with Cidofovir cleared their BK viruria between 21–54 days post-transplant. Of note, an additional 6 patients were identified who received Alem; overall 21/23 patients who received Alem developed BK viruria. In conclusion, we found an extremely high incidence of BK viruria (91%) in patients receiving Alem as conditioning therapy for allogeneic SCT. This was associated with ureteral stenosis or hydronephrosis in 4 patients. Therapy with cidofovir given at two different doses had no impact on the excretion of BK virus.