BK Virus-associated Hemorrhagic Cystitis Research Articles

BK virus-associated hemorrhagic cystitis in pediatric stem cell transplantation: a case report and scoping review.

BK virus-associated hemorrhagic cystitis (BK-HC) is a debilitating and poorly understood complication of hematopoietic stem cell transplantation (SCT). Hematuria, dysuria, and other symptoms associated with BK-HC are common in the immediate post-SCT period, making BK-HC difficult to distinguish from other conditions presenting with these symptoms. Despite published criteria for diagnosis, the degree to which these criteria are consistently applied to either clinical diagnosis or to studies informing BK-HC management is unclear. We present a case of BK-HC in a pediatric SCT recipient, and discuss the challenges associated with treatment in the absence of rigorous data to inform clinical management. We reviewed all cases of BK viruria at our center in patients undergoing SCT between January 2015 and December 2019. We then performed a scoping review of publications in PubMed addressing BK-HC, specifically focusing on how BK-HC was defined. Publications using the keywords "BK polyomavirus" and "hemorrhagic cystitis" were included if they involved a clinical study of SCT recipients and a full-text article was available in English. Case reports were excluded. Analysis focused on whether BK-HC was explicitly defined and whether the definition incorporated elements of diagnostic criteria published by European Conference on Infections in Leukemia (ECIL). A total of 30 studies published between January 2018 and 30 June 2021 met criteria for review, including 4 clinical trials, 7 prospective observational studies, and 19 retrospective observational studies. Fifteen of these studies included pediatric patients (7 pediatric only, 8 combined adult and pediatric). Of the 30 publications, 19 included a definition of either BK-HC or BK cystitis, with only five using ECIL criteria, all of which were observational studies. Multiple interventions are described for treatment of BK-HC, including cidofovir, leflunomide, quinolones, hyperbaric oxygen, keratinocyte growth factor, and BK-specific cytotoxic T lymphocytes. However, evidence to support efficacy for any of these interventions is lacking. Although BK-HC is a well-known complication of SCT, evidence to support available treatment options is limited. Well-controlled studies that incorporate clear diagnostic criteria are needed to better define the risk factors, natural history, and ideal interventions.

Risk factors for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.

BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients. We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC. Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR=1.32; 95% CI, 1.07-1.62; p=.009, I2 =34%), haploidentical donor (OR=1.84; 95% CI, 1.18-2.87; p=.007, I2 =23%), myeloablative conditioning (OR=1.76; 95% CI, 1.36-2.28; p<.0001, I2 =45%), acute graft versus host disease (aGVHD) (OR=2.73; 95% CI, 2.02-3.69; p<.0001, I2 =46%), chronic graft versus host disease (cGVHD) (OR=1.71; 95% CI, 1.12-2.60; p=.01, I2 =0%), and cytomegalovirus (CMV) reactivation (OR=3.13; 95% CI, 1.12-8.78; p=.03, I2 =79%) were significantly associated with BKV-HC in the univariable analysis. Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.

Decreased lymphocyte count before conditioning is associated with BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P<0.05. A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count<1×109/L before conditioning (OR=4.705, P=0.007) and haploidentical transplantation (OR=13.161, P=0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P=0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P=0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.

Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies.

Although post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, it is associated with toxicities, which might be dose-dependent. We compared the outcomes with PT-Cy at 80 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients undergoing haploidentical hematopoietic cell transplantation (HCT). Inclusion criteria included peripheral blood stem cells, hematological malignancy, and age>65 years (or age>60 years if cardiac event history). Thirty-eight patients received PT-Cy at 80 mg/kg and 55 100 mg/kg, divided in two doses. The cumulative incidences (CI) of acute grade II-IV, acute grade III-IV, and moderate/severe chronic GVHD were 32%, 16%, and 13% with PT-Cy at 80 mg/kg compared to 33%, 13%, and 16% with 100 mg/kg, respectively. In multivariable analysis, reducing PT-Cy dose had no significant impact on GVHD. Neutrophil and platelet engraftments were significantly improved, and CI of BK virus-associated hemorrhagic cystitis was reduced with 80 mg/kg of PT-Cy compared to 100 mg/kg. At 2 years, non-relapse mortality was 16% and 31%, progression-free survival 65% and 49%, overall survival 70% and 56%, and GVHD-free, relapse-free survival 52% and 36% with 80 mg/kg and 100 mg/kg, respectively. Reducing PT-Cy dose to 80 mg/kg is safe and associated with improved hematological recovery and lower CI of hemorrhagic cystitis in elderly patients undergoing haploidentical HCT.

Intravesical alprostadil as a promising agent in BK virus-associated hemorrhagic cystitis: A report of a refractory case.

Allogeneic stem cell transplant recipients are at risk of BK virus-associated hemorrhagic cystitis. This condition causes a significant morbidity and worsens clinical outcomes. The standard cares for BK virus-associated hemorrhagic cystitis are saline irrigation and forced diuresis. Notably, several beneficial roles are proposed for antiviral and anti-inflammatory agents against BK virus-associated hemorrhagic cystitis. However, cases who are at risk of cystectomy remain refractory. Herein, we present a 13-year-old boy with severe hematuria by passing two months from his allogeneic stem cell transplantation. The laboratory work up showed high BK viremia >1.1 × 108 copies/ml in this case's urine sample. The patient was treated with antiviral agents in combination with supportive care. Moreover, intravesical alum was administered, but no clinical benefits were achieved. Finally, intravesical alprostadil was prepared under the supervision of a pediatric clinical pharmacist. In this regard, an alprostadil solution was prepared by constitution of 250 μg alprostadil in 50 mL saline. After administrating the first dose of intravesical alprostadil, an acceptable clinical response was observed, and hematuria stopped. Of note, alprostadil induces platelet aggregation and vasoconstriction. Thus, bleeding can be controlled after the administration of intravesical alprostadil. This strategy may be associated with several side effects including bladder spasm. This study is the first report describing the special role of intravesical alprostadil in refractory cases of BK virus-associated hemorrhagic cystitis. In such refractory cases, clinicians can use intravesical alprostadil rather than invasive therapies in the treatment of BK virus-hemorrhagic cystitis.

Myeloablative Conditioning With PBSC Grafts For T-Replete Haploidentical Donor Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide Results In Universal Engraftment, Low Rates Of Gvhd, NRM and Excellent Survival Outcomes: An Analysis Of Two Consecutive Phase II Studies From a Single Center

Lack of a matched sibling or suitably matched unrelated donor can be a significant barrier to allogeneic hematopoietic cell transplantation in patients who stand to benefit from this procedure. HLA-haploidentical donors are readily available for nearly all such patients. Whereas previous attempts at haploidentical donor hematopoietic stem cell transplantation (haploSCT) using standard immunosuppression or ex-vivo T-cell depletion have had relatively poor outcomes, a recent approach using a T-replete bone marrow graft with non-ablative conditioning and post-transplant cyclophosphamide (ptCy) for control of alloreactivity has proved to be remarkably well tolerated (Luznik et al BBMT 2008). However, relapse of malignancy remains a major challenge with the use of this non-myeloablative regimen. The use of myeloablative conditioning and a PBSC graft may help reduce the relapse rate following T-replete haploSCT but this has not been well studied. We enrolled a total of 41 patients on two consecutive prospective phase II trials of myeloablative haploSCT and ptCy using a T-replete G-CSF mobilized PBSC graft. The first trial (NSH 864) employed a high-dose busulfan-based preparative regimen (fludarabine 30 mg/m2/d d-6 to -2, Busulfan 110-130 mg/m2/d d-7 to -3 , Cy 14.5 mg/kg/d d-6&-5) [n=20], the second (NSH 922) utilized a TBI-based regimen (fludarabine 25 mg/m2/d x 3 d and TBI 150 cGy bid on d -4 to -1 [total dose 1200cGy]) [n=21]. Post-grafting immunosuppression consisted of Cy 50mg/kg/day on days 3 and 4, MMF through d 35, and tacrolimus through d 180 on both protocols. Eligibility was limited to patients ≤60 years of age with aggressive/advanced hematologic malignancies perceived to be at high risk of relapse following nonmyeloablative transplant. Leukemia patients in CR1 were eligible if they had either poor-risk cytogenetics/molecular studies or primary chemoresistance. Median patient age was 45 years (range 24-60). Twenty-five patients were transplanted in complete remission (CR) or in chronic phase (CP), while 16 patients were transplanted with advanced disease. No patient experienced graft failure, with a median time to neutrophil and platelet recovery of 16 and 25 days, respectively. All evaluable patients achieved sustained complete donor T cell and myeloid chimerism by Day +30. Median follow-up for survivors is 20 months (NSH 864 - 39 months; NSH 922 – 11months). The cumulative incidence of grades II-IV and III-IV acute GVHD at day +100 was 30% and 17% respectively. The cumulative incidence of chronic GVHD at one year post transplant was 41% (severe in 9%). Non-relapse mortality (NRM) at 12 and 24 months was 8% and 17% respectively. Cumulative incidence of relapse was 31% at both 12 and 24 months post-transplant. The relapse rate was lower in patients transplanted in CR/CP (18%) vs. those transplanted with advanced disease (49%, p=0.044). BK virus-associated hemorrhagic cystitis (HC) occurred in 56% of patients, and was severe (requiring hospital admission for bladder irrigation and/or pain management) in 19%. The incidence of HC and severe HC was significantly lower in patients receiving TBI-containing conditioning than those receiving Busulfan (38% vs. 75%, p=0.028 and 10% vs. 30%, p=0.13, respectively). With a median follow-up of 20 months, the estimated 2 year overall survival (OS) was 51% with a 52% estimated disease-free survival (DFS). In patients transplanted in CR/CP, 2-year DFS was 64% vs. 35% in patients transplanted with advanced disease (p=0.077). There was an encouraging trend to better 2-year DFS in patients receiving TBI-based conditioning than those receiving Busulfan, 75% vs. 40%, p=0.072. Myeloablative haploSCT with PBSC grafts and ptCy allows reliable engraftment with early donor T cell chimerism; low rates of GVHD, infectious complications, and NRM; and promising survival in patients with high-risk hematologic malignancies. Outcomes are particularly good in patients treated in CR/CP (18% relapse, 64% DFS). When compared with Busulfan-based conditioning, TBI-based conditioning is associated with less risk of HC and improved DFS. Myeloablative haploSCT is a valid option for patients with aggressive/advanced hematologic malignancies who lack timely access to a conventional donor.▪▪ Disclosures:No relevant conflicts of interest to declare.

Efficacy of Cidofovir in Treatment of BK Virus Induced Hemorrhagic Cystitis in Post Allogeneic Hematopoietic Cell Transplant Recipients

Introduction:BK virus associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidence up to 70%. BK virus is a widely prevalent non-encapsulated DNA human polyomavirus which latently infects the uroepithelium and reactivates during immunosuppression. While its pathogenesis is not yet clearly elucidated, BK-HC is associated with factors related to transplant procedure (myeloablative conditioning regimen), graft source (unrelated donor, HLA mismatching), onset of acute graft-versus-host disease, and high-level urinary BK viral replication. Symptomatic and supportive measures have been the standard of care for many years for this difficult-to-treat complication. Treatments that have been trialed include antivirals, antibiotics, and immunomodulatory agents. Cidofovir is a nucleotide analog of cytosine that is active against various DNA viruses with growing evidence as a therapeutic option for BK-HC. The aim of the present retrospective study is to assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC.Methods:We conducted a retrospective study of the allo-HCT patient cohort from January 2010 until March 2017 in a single center in Ontario, Canada. All patients who underwent allo-HCT and received cidofovir for symptomatic BK-HC (hematuria with BK viruria and/or viremia) were included. Electronic charts were reviewed for patient characteristics, cidofovir prescription data, clinical outcomes, and toxicities. BK-HC severity was graded as: Grade 1 (microscopic hematuria), Grade 2 (macroscopic hematuria), Grade 3 (macroscopic hematuria with clots), Grade 4 (impaired renal function). Clinically efficacy was assessed at the end of cidofovir treatment as: Complete Response (CR) - complete symptom remission, Partial Response (PR) - downgrading of severity, or No Response - unchanged or worsening severity. The primary outcome was response to cidofovir, as defined by PR or CR. Secondary outcomes include overall survival, BK virus levels (both urine and blood), and renal toxicity (increase Cr > 30 µmol/L).Results:Twelve allo-HCT patients (6 male, 6 female; median age 49) with BK-HC were treated with cidofovir at our center. The majority of transplants were from 10/10 HLA matched related donors and complicated by acute GVHD and CMV viremia. Median time to BK-HC was 82 days (23-762 days), with an initial clinical grade of 3 (50%) or 4 (50%). All patients had BK viruria, whereas 2 did not have BK viremia. Prior therapies were received by most patients, specifically ciprofloxacin (75%) or leflunomide (17%). Cidofovir administration was via intravenous (33%), intravesical (58%), or both modalities (8%). Median cumulative dose was 10 mg/kg (1-37 mg/kg) across a median of 2 doses (1-21 doses) with a median of 3.25 days (1-30 days) between doses. Mean BK-HC grade decreased significantly by 1.8 (3.5 pre-cidofovir, 1.7 post-cidofovir, p<0.01). Overall, 66% of patients had response to cidofovir (CR=4, PR=4), with similar response rates between intravenous (66%) and intravesical (62%) administration. Two patients had reemergence of BK-HC after showing an initial response. Over the study period, 67% of patients died. Renal toxicity was experienced by 33% of patients; 3 patients had acute kidney injury (2 receiving intravesical, 1 receiving both modalities). Further complications included keratitis, Fanconi's syndrome, and pseudomonal sepsis after intravesical administration.Discussion:In our retrospective institutional review, a majority of patients achieved at least partial remission after cidofovir treatment with similar response rates between intravesical and intravenous administration. While the rate of CR was lower in our study (33%) than previous studies (60-100%), only severe BK-HC cases were included. Nonetheless, there was an overall significant reduction in BK-HC severity with cidofovir administration. While avoidance of systemic toxicity is a purported benefit of intravesical instillation, amongst patients receiving intravesical cidofovir, acute kidney injury as a possible complication needs to be considered. While cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk Assessment for BK Virus-Associated Hemorrhagic Cystitis After Pediatric Hematopoietic Stem Cell Transplant: A Single-Center Retrospective Cross-Sectional Study.

BK virus-associated hemorrhagic cystitis is a common complication of allogeneic hematopoietic stem cell transplant. It is known to be associated with cyclophosphamide therapy and the intensity of the conditioning regimen as well as infection with the BK virus. Data are limited for BK virus-associated hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Therefore, we aimed to identify the risk factors and etiology of BK virus-associated hemorrhagic cystitis and determine the factors that may improve the treatment efficacy. Data from recipients of allogeneic hematopoietic stem cell transplant were retrospectively analyzed. These data included information about age, sex, underlying disease, the details of ablative conditioning, graft-versus-host disease prophylaxis, donor type, stem cell source, history of acute graft-versus-host disease, and cytomegalovirus reactivation. A total of 50 patients developed BK virusassociated hemorrhagic cystitis among 334 patients. Symptoms associated with BK virus-associated hemorrhagic cystitis manifested an average of 45.3 days after transplant. Most of the patients had grade 2 and grade 3 hemorrhagic cystitis. Risk factor analysis revealed that haploidentical donor type, treatment with busulfan and cyclophosphamide as part of conditioning regimen, and history of total body irradiation increased the risk of BK virus-associated hemorrhagic cystitis in the pediatric recipient population. We found that, despite current conditioning regimens, BK virus-associated infection still leads to a considerable incidence rate of hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Patients with a haploidentical donor and a history of busulfan and cyclophosphamide treatment or total body irradiation had a higher risk of BK virus-associated hemorrhagic cystitis. Thus, we suggest that patients with these factors should be followed closely after allogeneic hematopoietic stem cell transplant.

BK Virus Epidemiology, Risk Factors, and Clinical Outcomes: An Analysis of Hematopoietic Stem Cell Transplant Patients at Texas Children's Hospital.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). A retrospective review was performed to determine the frequency of BKV-HC and identify risk factors and renal morbidity associated with BKV-HC in pediatric HSCT recipients at our institution. A total of 314 pediatric recipients underwent allogeneic HSCT for either malignant (173, 55.1%) or nonmalignant disorders (141, 44.9%) from January 1, 2011, to December 31, 2015, with a minimum follow-up of 5 years post-HSCT. Severe BKV-HC (grades 3 and 4) was prevalent in 46 out of 67 (68.7%) recipients. Timing to presentation of severe BKV-HC (grades 3 and 4) occurred at a median of 37 days (26, 74; IQ1, IQ3) post-HSCT, with the duration of macroscopic hematuria lasting a median of 37.5 days (18, 71; IQ1, IQ3). In the first 60 days post-HSCT, peak acute kidney injury (AKI) stages 2 and 3 were seen more frequently in HSCT recipients who developed BKV-HC than those without (P = .004). Similarly, during post-HSCT days 61 to 100, peak AKI stage 3 was also more frequently seen in HSCT recipients who already developed BKV-HC prior to or during this time period than those without BKV-HC (P = .0002). Recipients who developed BKV-HC within 1 year of HSCT had more frequent mild to moderate chronic kidney disease (CKD stages 2-3) than those without BKV-HC (P = .002 and .007, respectively). On multivariate analysis, BKV-HC was associated with all-cause mortality (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.35-3.65). The following clinical variables were associated with time to development of HC on multivariate analysis: age (subdistribution HR [sHR] 1.11; 95% CI: 1.06-1.16) and myeloabalative conditioning regimen (sHR 4.2; 95% CI: 2.12-8.34). Pediatric HSCT patients with BKV-HC experience significant morbidity and mortality. Renal morbidity, including AKI and CKD, is associated with BKV-HC.

Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in Chronic Granulomatous Disease.

Haploidentical related donor (HRD) transplantation was performed in 7 recipients with chronic granulomatous disease (CGD) who had no matched-related or unrelated donor. Peripheral blood cell (PBC) products were used with a conditioning regimen consisting of low-dose cyclophosphamide, fludarabine, total body irradiation, and busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of high-dose post-transplant cyclophosphamide and sirolimus. Recipients were ages 14-26years, and 3 had severe infections active at transplant. All 7 recipients achieved full engraftment with complete donor chimerism early in the post-transplant period. Acute GVHD occurred in all cases and was grade 3 or steroid refractory in 3. Two patients with steroid-refractory GVHD died. Three patients with severe infectious complications active at transplant, 1 Nocardia pneumonia and 2 extensive invasive fungal infections), survived and were cured of their infection at last follow-up. Bacterial disease occurred post-transplant in all recipients, and viral infections/reactivation were common, including 4 cases of BK virus-associated hemorrhagic cystitis. Seven patients with CGD achieved rapid and full-donor engraftment from HRDs utilizing PBCs and a conditioning regimen with PTCy and sirolimus GVHD prophylaxis. However, the incidence of grade 3 and steroid-refractory GVHD was high and led to 2 deaths. Patients with active infections at transplant had successful transplant courses and were cured of their disease. Although there was an initial success with this regimen, the cumulative experience does not support its use in CGD due to an unacceptable rate of severe GVHD.

BK Virus-Associated Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplantation (HCT) Recipients with Primary Immunodeficiency

Allogeneic HCT recipients may develop BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC), typically early after engraftment. Yet, BKV levels in urine and blood are not routinely monitored pre- or post-HCT. Among HCT recipients with primary immunodeficiency diseases (n=40), we prospectively monitored BKV levels by quantitative PCR in blood and urine pre-HCT, as well as weekly post-HCT through day +100 on NCT02579967. Thirty patients were considered at-risk for BKV-HC based on BKV detection in urine/blood at any timepoint. Of these, 22 (73%) developed BKV-HC. Of recipients treated on the reduced-intensity conditioning (RIC) busulfan-containing arms of the trial, 22 of 27 (81%) at-risk patients developed BKV-HC (Fig 1). By contrast, on the non-myeloablative conditioning arms, identical to RIC except for the absence of busulfan (Fig 2), 0 of 3 at-risk patients developed BKV-HC (p=0.01). No patients received antiviral or cellular therapies for BKV-HC, although 3 received cidofovir and/or brincidofovir for adenovirus infection. Three required continuous bladder irrigation; 1 required multiple cystoscopies for clot evacuation but no intravesicular therapy. Disease outside the bladder was rare: 1 patient (Fig 1 - P36, with notably atypical pattern of BKV levels in relation to symptoms) developed tissue-proven BKV nephropathy, along with radiographic and cytopathologic (SV40+ cells on bronchoalveolar lavage) evidence of BKV pneumonitis; thus, further evaluation for extravesicular disease, particularly in those without significant gross hematuria, is under way. Patient discomfort and supportive care needs were significant, especially during gross hematuria (n=19; median duration 21 days, range 2-41; see Fig 1). With neutrophil engraftment at median day +17 (range 13-42), median onset of BKV-HC symptoms was day +22 (range +5-74), with median duration of 26 days (range 6-145 days). Starting on day +21, the trajectory of urine BKV levels diverged between RIC-HCT recipients with or without BKV-HC (Fig 3), with significantly higher BKV in urine at day +28 for BKV-HC patients, median 8.98 log10 IU/mL, compared to those without, median 4.99 log10 IU/mL, Mann-Whitney p=0.02. At BKV-HC onset, median level of BKV in urine was 9.66 log10 IU/mL (range 6.01 to >9.81) and, at full resolution, 8.39 log10 IU/mL (range 2.87 to >9.81). Swimmer's plot (Fig 1) shows the peak in urine BKV to occur soon before or early into symptom onset in most and that blood BKV peak levels vary more in timing. In conclusion, in this cohort, the use of busulfan seems to be an important co-factor in BKV-HC risk, as also noted by others. The trajectory of BKV levels in urine differed between those with and without BKV-HC, although the identification of early BKV-HC predictors is limited by the short interval between divergence in case/control values and symptom onset.

Intravesicular Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation.

Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC.

Third-Party BK Virus Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation

Background. BK virus associated hemorrhagic cystitis (BKV-HC) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT), [Bedi, A., et al. JCO 1995] particularly in recipients of alternative donor transplants, which are being performed with increasing frequency [O'Donnell, P.H., et al, BBMT 2009]. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, with few effective therapeutic options [Seber, A., et al., BMT 1999]. Methods. We assessed the feasibility, safety, and efficacy of administering most closely human leukocyte antigen (HLA)-matched third party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 47 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. We compared their toxicity and survival to a control group of 85 AHSCT patients with BKV-HC treated with standard of care, using inverse probability of treatment weighted (IPTW) estimation to correct for bias due to non-randomization. The control group was matched for age, gender, graft versus host disease prophylaxis, conditioning regimen, AHSCT graft source, and both initial and maximum grade of BKV-HC. Results. On average, BKV disease status improved from 7 to 90 days post CTL infusion, with the primary response endpoint scored on day 28. Among 31 evaluable patients on day 28 who received a single BKV CTL infusion, 18 had a complete response (CR) and 9 a partial response (PR), for an overall response rate of 87%, which increased to 100% among evaluable patients at day 90 (Figure 1). Four of 7 patients who received multiple (1-5) CTL infusions for persistent disease following the first infusion are alive without BKV-HC. Median survival from the date of transplant in the BKV CTL group was 772 days, compared to a median of 171 days for the controls (IPTW adjusted log rank test p-value = 0.02) as shown in Figure 2. One BKV CTL patient with a history of skin graft versus host disease (GVHD) developed grade 3 gastrointestinal GVHD 64 days post CTL infusion, which resolved completely with systemic steroids. There were no cases of graft failure or infusion-related toxicities. BKV CTLs were identified in patient blood samples up to one month post-infusion. Conclusion. This is the largest series of AHSCT patients treated to date with BKV CTLs. The high response rate we observed in this study appeared to confer a survival benefit compared to a historically controlled cohort with BKV-HC treated with standard of care alone. This study demonstrated that administering third party, off-the-shelf banked BKV CTLs is feasible and safe. The safety profile, high response rate, and logistical ease with which potent off-the-shelf BKV CTL therapy were generated and administered warrants further investigation for patients with BKV-HC who have limited alternative therapeutic options. Disclosures Chemaly: ADMA Biologics: Other: Personal fees; Gilead: Research Funding; Janssen: Other: Personal fees; Ansun: Other: Personal fees; Oxford Immunotec: Research Funding; Chimerix: Research Funding; Ablynx: Other: Personal fees; Merck: Research Funding; Clinigen: Other: Personal fees; Gilead: Other: Personal fees; Ansun Pharmaceuticals: Research Funding; Chimerix: Other: Personal fees; Oxford Immunotec: Other: Personal fees; Merck: Other: Personal fees; ReViral: Other: Personal fees. Ciurea:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder; MolMed: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding. Kebriaei:Kite: Honoraria; Jazz: Consultancy; Pfizer: Honoraria; Amgen: Research Funding. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding. Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Champlin:Sanofi-Genzyme: Research Funding; Actinium: Consultancy; Johnson and Johnson: Consultancy.

Increased risk of 100-day and 1-year infection-related mortality and complications in haploidentical stem cell transplantation.

Background: While haploidentical transplantation has led to the near-universal availability of donors, several challenges for this form of transplant still exist. This study sought to investigate the rates of infection-related mortality and other complications following haploidentical vs nonhaploidentical transplant.Methods: We conducted a retrospective cohort study in adults with various malignant and benign hematological conditions who underwent allogeneic hematopoietic stem cell transplantation from 2011 to 2018. One hundred-day and 1-year overall survival were defined as survival from the time of transplant until 100 days or 1 year later.Results: A total of 187 patients were included in this study, with 45 (24.1%) receiving transplants from haploidentical donors and 142 (75.9%) from nonhaploidentical donors. There were similar rates of acute graft-versus-host disease (GVHD) (40% vs 38% in haploidentical vs nonhaploidentical recipients, P=0.86) and chronic GVHD (44.4% vs 43.7%, P=1). Rates of 100-day and 1-year infection-related mortality were significantly higher in the haploidentical group compared to the nonhaploidentical group (8.9% vs 1.4% at 100 days, P=0.03, and 15.9% vs 3.8% at 1 year, P=0.01). There were also higher rates of cytomegalovirus infections (59.1% vs 23.8%, P<0.01), BK virus-associated hemorrhagic cystitis (40.9% vs 8.4%, P<0.01), and BK viremia (15.9% vs 0.8%, P<0.01) in haploidentical recipients.Conclusions: Despite the use of identical antimicrobial prophylactic and treatment agents, haploidentical recipients were found to have significantly increased rates of 100-day and 1-year infection-related mortality as well as several other infectious complications.

Post Transplantation Cyclophosphamide (PTCY) Is Associated with Increased Risk of BK Virus-Associated Hemorrhagic Cystitis (BKHC) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT).

Introduction BK virus hemorrhagic cystitis is a well-recognized complication in patients undergoing allogeneic HSCT and is associated with significant morbidity. PTCY has been used for GVHD prophylaxis in patients undergoing haploidentical or mismatched unrelated donor HSCT. We hypothesized that PTCY is associated with increased incidence of HC associated with BK virus. Objectives • To identify the risk factors for developing BKHC in allogeneic HSCT • To assess the effect of PTCY in development of BKHC in patients with myeloablative (MA) regimen containing total body irradiation (TBI) • To evaluate the risk of concurrent CMV infection and BKHC in allogeneic HSCT with MA conditioning regimen Methods We identified 116 consecutive patients who underwent allogeneic HSCT at our institution between January 2015 and July 2018. The MA regimen (n=42) consisted of fludarabine 50 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 4 days with or without TBI of 200 cGy/day for 2 days (FBT or FB4). The reduced intensity conditioning (RIC) regimen (n=74) consisted of fludarabine 30 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 2 days (FB2). In terms of GVHD prophylaxis all recipients except those undergoing haploidentical and mismatched unrelated transplant received Thymoglobulin 2 mg/kg/daily IV days -2, -1 and 0 (n=80). Recipients of haplo- related and mismatched unrelated donor transplantation received cyclophosphamide 50 mg/kg IV on day +3 and +4 along with Mesna (n=36). All patients received post-transplant immunosuppression with Tacrolimus and Mycophenolate Mofetil. Patients with urinary symptoms were tested for BKV in urine by PCR. Results The median age of patients was 56 years (range 20–76). A total of 31% of patients (n=13) received PTCY in FBT group which was similar to 31% of patients (n=23) in FB4-FB2 (p=0.98). Overall 21.5% patients were diagnosed with BKHC. The patients who received ATG, the incidence of BKHC was 27.5% in FBT group and 11.7 % in FB4-FB2 (p=0.073). The patients who received PTCY, the incidence of BKHC was significantly increased to 69.2% in FBT vs 9% in FB4-FB2 (p=0.0001). The risk of developing concurrent CMV viremia and BKHC was increased to 10.3% in FBT compared to 5.8% in FB2-FB4 (p=0.662). The patients who received PTCY following FBT, the incidence of concurrent CMV viremia and BKHC was increased to 23.1%. as compared to 0% with FB2-FB4. Conclusion Our result shows the addition of PTCY to TBI containing regimen significantly increased the incidence of BKHC. We did not observe increase in the incidence of BKHC in patients receiving PTCY with FB2 or FB4 regimens. Our study revealed an increased incidence of concurrent BKHC and CMV viremia in patients receiving PTCY with FBT which could be due to increased immunosuppression. Our findings suggest that using PTCY as GVHD prophylaxis in patients undergoing MA conditioning regimen including TBI is a risk factor for BKHC.

Increased Rates of BK Virus-Associated Hemorrhagic Cystitis and BK Viremia in Haploidentical Stem Cell Transplantation

Introduction In haploidentical transplantation, increased infectious risk compared to matched related donor (MRD) and matched unrelated donor (MUD) transplants is a complication that contributes to patient morbidity and mortality. This study investigated the 1-year post-transplant rates of BK virus-associated hemorrhagic cystitis and BK viremia in the haploidentical population compared to the non-haploidentical population. Objectives The objectives of this study were to compare the rates of BK virus-associated hemorrhagic cystitis and BK viremia in haploidentical patients compared to MRD and MUD patients within 1 year after transplant. In addition, we investigated whether patients with BK virus-associated hemorrhagic cystitis were at higher risk for also developing BK viremia in the haploidentical population. Methods This was a retrospective study that analyzed the outcomes of patients who underwent allogeneic stem cell transplants from haploidentical donors, MRD, or MUD. BK virus infection was assessed through urine samples and via a quantitative serum detection test. Statistical analysis was performed using the Fisher Exact Probability Test with p-values Results Out of 174 transplant patients, 44 (25%) transplants were from haploidentical donors and 130 (75%) from non-haploidentical donors (MRD and MUD). BK viruria was detected in a significantly higher amount of haploidentical patients, with 15 (34%) haplo and 13 (10%) non-haplo patients affected (p = 0.004). All cases of BK viruria were associated with hemorrhagic cystitis. The rate of BK viremia was also significantly higher in the haploidentical population, affecting 7 (16%) haplo patients vs. 1 (0.1%) non-haplo patient (p Conclusion Our results indicated that amongst the haploidentical population, there were significantly higher rates of BK virus-associated hemorrhagic cystitis and BK viremia compared to the non-haploidentical population. In addition, out of all allogeneic transplant patients who were found to have BK viruria, a frequently reported infection in the transplant population, haploidentical patients were at greater risk of developing BK viremia as well. These findings were also in the context of similar rates of GVHD between haplo and non-haplo patients, indicating that the higher rates of infections were not due to increased GVHD immunosuppression. Further investigation is warranted to confirm these findings and propose prophylactic approaches to BK virus infections in the haploidentical population.

Intravesicular Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis (BKV-HC) Following Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Background: BKV HC is a well-known complication following allo-SCT. Supportive care with bladder irrigation and blood transfusions were the only available treatment. Since our initial report (Bridges B et al. Am J Hematol 2006;81:535), several studies confirmed that intravesicular cidofovir is a potential effective treatment for BKV HC. In this study, we report a large series of consecutive patients who developed BKV HC following allo SCT and received intravesicular cidofovir.Methods: We conducted a retrospective review of allo SCT patients who developed BKV HC and were prescribed intravesicular cidofovir from 2012 to 2017.Results: 33 patients were diagnosed with BKV HC. The median age was 50 years (range=23-73), and 18 (55%) were male. Acute myeloid leukemia (n=12, 35%) was the most common diagnosis followed by non-Hodgkin lymphoma (n=7, 21%) and B cell acute lymphoblastic leukemia (n=4, 12%). Conditioning regimens were myeloablative (n=19, 58%) or reduced-intensity (n=14, 42%); 15 (45%) patients received cyclophosphamide, and 22 (67%) received total body irradiation. The median time to onset of HC symptoms following SCT was 37 days (range: 8-178); 17 (52%) patients had acute graft vs. host disease. HC symptom severity ranged from grade 0-4 (median=2). The median BK urine viral load pre-treatment was 100,000,000 IU/ml. Patients received a median of 2 intravesicular treatments (range=1-7) at a dose of 5 mg/kg. Four patients (12%) were also treated concurrently with intravenous cidofovir. 19 (59%) patients demonstrated complete clinical resolution of symptoms, 9 (28%) demonstrated partial response to treatment, and 4 (13%) had no change in symptoms following treatment. These improvements in clinical status were independent of viral load, though most had reductions in the viral load. The median time to symptom resolution was 17 days (range=7-53; n=28). 82% of patients had no recurrent symptoms of HC. The main side effect of intra-vesicular instillation was increased discomfort and bladder spasms; severe in 3 patients (9%). No patient had impaired renal function directly attributable to intra-vesicular cidofovir. At 12 months after BKV HC diagnosis, 26 (79%) patients were alive.Conclusions: To our knowledge this is the largest study of intravesicular cidofovir for BKV HC reported to date; 77% of patients with BVK HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for adding intravesicular cidofovir as a standard tool for the treatment of BKV HC. DisclosuresBadros:Celgene: Consultancy, Research Funding; Karyopharm: Research Funding; GSK: Research Funding.

Reduced Dose of Post-Transplant Cyclophosphamide for HLA Haploidentical Peripheral Blood Stem Cell Transplantation

[Introduction]Allogeneic hematopoietic stem cell transplantation (Allo-SCT) remains the only potentially curative therapy for patients with high-risk or chemo-refractory hematologic malignancies. Recently, various methods including post-transplant cyclophosphamide (PT-CY) showed the ability to overcome the HLA disparity barrier and haploidentical hematopoietic stem cell transplantation (haplo-SCT) have been becoming an attractive method of transplantation with less rejection or graft-versus-host disease (GVHD). There have been many reports that the outcomes of haplo-SCT are equivalent to those of matched related donors and matched unrelated donors. The standard dose of PT-CY is 50 mg/kg/day for 2 days. However, optimal dose of PT-CY has not been studied extensively. In this study, we performed a clinical study of reduced dose of PT-CY (40 mg/kg/day for 2 days) haplo-SCT for hematologic malignancies.[Methods]We included adult patients with hematologic malignancies who received haplo-SCT at Kurume university hospital, Kurume, Japan between Oct 2014 and March 2018. Myeloablative conditioning (MAC) regimen consisted of fludarabine (Flu) (30 mg/m2 for 5 days), busulfan (BU) (3.2 mg/kg/day for 4 days) and total-body irradiation (TBI) 4Gy (Flu/BU4/TBI4Gy) or Flu (30 mg/m2 for 3 days) and TBI 12Gy (Flu/TBI12Gy). Reduced-intensity conditioning (RIC) regimen consisted of Flu (30 mg/m2 for 5 days), BU (3.2 mg/kg/day for 2 days) and TBI 4Gy (Flu/BU2/TBI4Gy). All patients were given PT-CY (40 mg/kg/day) on day +3 and day +4, followed by tacrolimus and mycophenolate mofetil (MMF) starting on day + 5 for GVHD prophylaxis. If there was no active GVHD, MMF was tapered off from day +30. Filgrastim 300 ug/m2 was administered starting on day +5 and continuing until neutrophil engraftment was achieved. Donors were mobilized with filgrastim 400 ug/m2 for 4 or 5 days, the peripheral blood stem cells were collected with one or two apheresis procedures. OS and PFS were calculated using the Kaplan-Meier method and the log-rank test was used for comparisons of Kaplan-Meier curves. Estimates of acute GVHD was calculated using death as the competing risk. P-values <0.05 were considered statistically significant.[Results]A total 15 patients with acute myeloid leukemia (AML, n=6), myelodysplastic syndrome (MDS, n=2), acute lymphoblastic leukemia (ALL, n=4), adult T-cell leukemia/lymphoma (ATLL, n=1) and malignant lymphoma (ML, n=2) were analyzed in this study. Patients median age was 54 years (range, 17 to 72); 9 patients were male, and 6 patients were female. Eight patients received MAC, 7 received RIC conditioning regimen. Disease status at transplantation was complete remission (CR) in 8 patients, non-CR in 7. The median CD34+ cell dose was 5.9 x 106 /kg (range, 2.4 to 17.4). All 15 patients achieved a neutrophil engraftment in a median 15 days (range, 13 to 19). Grade II-IV and III-IV acute GVHD occurred in 46.7% (95% confidence interval [CI], 14.4-66.8) and in 13.3% (95% CI, 0-28.9) patients, respectively. At 2 years, overall survival (OS) and progression-free survival were 36.6% (95% CI, 13.0-60.9) and 32.0% (95% CI, 10.9-55.7), respectively. The 2-years OS of patients in CR before SCT was 50.0% (95% CI, 15.2-77.5) compared to 28.6% (95% CI, 4.1-61.2) not in CR (P=0.106). The causes of death were: disease progression (n = 3), infection (n = 3), acute GVHD (n = 2), and noninfectious pulmonary complications (n = 2). Among infectious complications, two were bacterial infections and one was BK virus-associated hemorrhagic cystitis.[Conclusion]Reduced dose of PT-CY HLA haploidentical peripheral blood stem cell transplantation resulted in acceptable rate and severity of acute GVHD. However, relapse and infection remain major problems after PT-CY haplo-SCT for hematologic malignancies. DisclosuresNo relevant conflicts of interest to declare.

1560. Clinical Presentation of BK Virus-Associated Hemorrhagic Cystitis (HC) After Hematopoietic Cell Transplantation (HCT)

BackgroundBK polyoma virus (BKPyV) has been associated with hemorrhagic cystitis after HCT. Prior studies have examined risk factors for BKPyV-associated HC, but the characteristics of disease, including duration, common presentations, and the spectrum of clinical outcomes, have not been well described. Precise estimates of major clinical endpoints are critical to design clinical trials of novel prevention and treatment agents.MethodsWe retrospectively analyzed HCT patients between 2007 and 2017. Subjects were included if they had macroscopic hematuria (Bedi grade ≥2), a positive urine BKPyV PCR, and at least one plasma BKPyV viral load available after platelet engraftment or Day 28 post-HCT. HC was defined by hematuria and positive urine BKPyV PCR; duration was determined by time to resolution of hematuria. Demographic data, baseline symptoms, and clinical outcomes (e.g., need for bladder irrigation, use of cidofovir) were reviewed.ResultsBKPyV-HC developed in 149 HCT recipients (97.3% allogeneic, 73% myeloablative conditioning) at a median of 54 days post-transplant (IQR 40–73). Seven percent were co-infected with adenovirus at the time of diagnosis. Symptoms and outcomes are shown in Table 1. Of those with plasma viral load testing at the onset of HC, 91% (112/126) had BKPyV viremia with a median viral load of 2,200 copies/mL (IQR 385–9,300). Twenty-nine percent of the cohort received cidofovir.ConclusionWe describe the characteristics of BKPyV-associated HC in HCT recipients in the modern era of immunosuppression. BKPyV-associated HC is a morbid disease in need of improved management strategies; patient-centered estimates of outcomes are crucial for evaluating new agents.Table 1.Symptoms and outcomes of BKPyV-associated HCBKPyV- HC n = 149 (%)Clots in urine*92 (60)Dysuria*124 (81)Frequency*91 (59)Urgency*68 (44)Flank pain*22 (14)Abdominal pain*30 (20)Median duration of symptoms in days (IQR)25 (14–49)Median duration of hematuria or urine clots in days (IQR)18 (12–39)Median duration of phenazopyridine or oxybutynin use in days (IQR)19 (8–34.5)Need for pain medication†109 (71)Need for Foley placement†49 (32)Need for continuous bladder irrigation†26 (17)Need for surgical intervention†9 (6)*At presentation. †Any time during course.Disclosures S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. A. Limaye, Novartis: Consultant, Consulting fee. M. Boeckh, Vir Biotechnology: Consultant and Grant Investigator, Consulting fee and Research grant; Chimerix Inc: Consultant, Grant Investigator and Investigator, Consulting fee, Research grant and Research support.

Efficacy of Cidofovir in Treatment of BK Virus–Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients

BK virus–associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.