Treatment Of BK Virus Infection Research Articles

Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

Research Progress on BK Virus Infection after Hematopoietic Stem Cell Transplantation--Review

BK virus infection is one of the common complications after hematopoietic stem cell transplantation(HSCT), which is also one of the reasons of the hemorrhagic cystitis．In recent years, although there are more studies of the risk factors related with human BK virus infection after hematopoietic stem cell transplantation, the risk factors related with BKV-associated hemorrhagio cystitis(BKV-HC) remain to be elucidated. Diagnosis of BK virus infection is mainly based on quantitative PCR of blood or urine. An effective strategy for treatment of these patients is the adoptive transfer of T lymphocytes specific to virus-associated antigens. In this review, the progressis of diagnosis and treatment of BK virus infection after hematopoietic stem cell transplantation are briefly summarized.

BK Virus Disease Following Allogeneic Stem Cell Transplantation: A Cohort Analysis

Abstract 1927BK virus (BKV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) affects the genitourinary (GU) tract with manifestations ranging from asymptomatic viruria to severe hemorrhagic cystitis. Knowledge about epidemiology, morbidity and clinical spectrum of BKV disease is limited. We studied a recent HSCT cohort at our institution to assess and quantify the incidence and severity of BKV disease.Between January 1, 2010 and December 31, 2011, 491 patients underwent first HSCT. BKV disease was defined as detection of BKV by PCR testing in association with GU symptoms. BKV disease was considered severe when patients had at least 1 of the following: hematuria with clot formation, GU tract inflammation on imaging, need for invasive GU interventions, or hospitalization for BKV disease management. Medical records were reviewed for patient and HSCT characteristics. For patients with BKV disease, reason for testing, clinical presentation and course, imaging results, and treatments were captured. Time at risk was censored at time of death, second HSCT or on July 1, 2012. Fisher's exact or Wilcoxon test were used to compare variables. Cox modeling was used to analyze potential risk factors for BKV disease.168 (34.2%) patients were tested for BKV at our institution during the study period. Median time to testing was 61 days (range, 2–663; IQR 19.5 – 114). 88 patients (17.9%) were diagnosed with BKV disease with an incidence rate of 0.54/1000 patient-days (95% CI, 0.43 – 0.66). Most common symptoms at presentation and during a first BKV disease episode are shown in the Table.TableCommon symptoms of BKV disease (n=88).SymptomAt presentationDuring first episodeDysuria45 (51.1%)59 (67.0%)Hematuria31 (35.2%)42 (47.7%)Urinary frequency16 (18.2%)40 (45.5%)Urgency10 (11.4%)21 (23.9%)Bladder spasms3 (3.4%)15 (17.0%)Flank pain3 (3.4%)11 (12.5%)31 patients had severe BK disease (35.2%, 6.3% of the cohort): 17 patients (19.3%) had hematuria with clot formation; 16 patients (18.2%) demonstrated GU tract inflammation on imaging studies, including bladder wall (14, 15.9%) or ureteral (5, 5.7%) thickening. 4 patients were hospitalized for management of BKV associated symptoms. Invasive GU interventions were performed in 16 (18.2%) patients including Foley catheter placement in 12, bladder irrigation in 7, intravesicular cidofovir in 3, cystoscopy in 2, and alum instillation in 1. Additional prescribed treatments during BKV disease episodes included quinolones (39, 44.3%), antispasmodics (29, 33.0%), IVIG (20, 22.7%) and pain medications (18, 20.5%). Cidofovir was used in 7 (8.0%) patients and leflunomide in 8 (9.1%). 3 patients had concomitant bacterial GU infections; 1 patient had GU adenovirus disease. Patients (n=71) were symptomatic for a median of 31 days (range 2–385, IQR 9–67). Additional BKV disease episodes were seen in 26/88 patients (29.5%).Median initial urine BKV load was 3.4×108 copies/mL (range; 600, >1×1010). Median peak urine BKV load during first BKV disease episode was 1.5×109 c/mL (range; 600, >1×1010). Blood BKV loads were obtained in 35 patients, with median initial BKV load of 800 c/mL (range, 0, 1.52×106) and median peak BKV load of 2000 c/mL (range, 0, 1.52×106). Detection of BKV viremia was 74% sensitive and 38% specific for severe BKV disease.Cohort characteristics associated with increased BKV disease risk included myeloablative conditioning (p=0.01), cyclophosphamide conditioning (p=0.0008), cord blood HSCT (p=0.03), GVHD prophylaxis with mycophenolate (MMF, p=0.0006) and acute GVHD (aGVHD) grades II-IV (p< 0.0001). On multivariate Cox modeling, time-dependent aGVHD (adjusted HR [aHR] 3.65, 95%CI 2.23 – 5.97), MMF use (aHR 3.11, 95%CI 1.76 – 5.48), and cyclophosphamide use (aHR 1.95, 95%CI 1.25 – 3.04) remained significant. Time-dependent aGVHD (aHR 5.02, 95%CI 2.20 – 11.5), cord blood HSCT (aHR 4.60, 95%CI 1.67 – 12.7) and cyclophosphamide use (aHR 2.17, 95%CI 1.04 – 4.56) were independent risk factors for severe BKV disease.BKV disease is a common complication of HSCT, associated with significant and prolonged morbidity, especially in the setting of aGVHD, cyclophosphamide and MMF use, and after cord blood HSCT. Prospective studies are needed to better define the morbidity of BKV disease and to properly inform the impact of future prophylaxis and treatment trials. Disclosures:Off Label Use: ciprofloxacin, levofloxacin, moxifloxacin, cidofovir, leflunomide use for treatment of BK virus infection. Marty:Chimerix: Consultancy, Research Funding.

Clinical diagnosis and treatment of BK virus infection in renal transplant recipients

To explore methods of clinical diagnosis and treatment of BK virus (BKV) infection in renal transplant recipients. Urine samples were collected from 227 renal transplant recipients who had undergone renal transplantation at most 48 months to detect the decoy cells. Samples of urine and peripheral blood (BP) were collected to undergo real-time PCR to detect the BKV DNA. Part of the renal-recipients received graft biopsy. The recipients with BKV viruria or viremia were divided into 2 groups: intervention group and control group. The 51 patients of the intervention group had the doses of cyclosporine A (CsA) reduced (n=19), had their doses of FK506 reduced (n=22), or underwent replacement of FK506 with CsA (n=10). And other 29 patients in the control group did not receive any intervention. Acute rejection was intensively monitored. The amount of decoy cells, and BKV load in the urine and PB samples were measured again after 3 months. The positive rates of urine decoy cell, BKV viruria, and viremia in all patients were 33.0%, 33.5%, and 15.4% respectively. In the intervention group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB before intervention were 5.0/10 HP, 1.50 x 10(4) copies/ml and 0 copy/ml respectively ; and the median levels of decoy cell in urine, and of BKV DNA in urine and PB were all 0 after intervention, all significantly lower than those before intervention (all P < 0.01). In the control group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB were 6.0 /10 HP, 0.79 x 10(4) copies/ml, and 0 copy/ml respectively before observation, and the median level of BKV load in urine ofter observation was 2.21 x 10(4) copies/m, significantly higher than that before observation (P < 0.01), however, the median levels of decoy cells in urine and of BKV DNA in PB were 5.0 /10 HP and 0 copy/ml respectively, not significantly different from those before observation ( both P > 0.05). The differences between the levels of urine decoy cells, urine BKV DNA level and blood BKV DNA level of the intervention group were all significantly greater than those of the control group (Z = -2.749, -5.089, -1.996; P = 0.006, 0.000, 0.046 respectively). And during the intervention no acute rejection was observed. Four cases of BKVAN were diagnosed. Treatment of immunosuppression reduction showed effectiveness in 4 BKVAN recipients. The levels of decoy cells in urine, and BKV load in urine and in PB samples were all decreased. The graft functions were improved. Urine cytology is very convenient, useful and sensitive for the evaluation and followup of renal transplant patients, and can reflect renal histological presentation indirectly. Also BKV DNA detection in the urine and peripheral blood is important to screen the evidence of BK reaction in order to prevent irreversible graft damage of BKVAN. The treatment of immunosuppressant reduction and replacement of FK506 with CsA are effective in BKV infection recipients at the early stage.