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Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy., Competing Interests: Declarations Funding: No external funding was received. Competing Interests: There are no conflicts of interest for all authors. Ethical Approval: Not required. Sequence Information: N/A., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients., Objective: This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT., Methods: Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT., Results: A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×10 7 (5.37×10 2 to 6.84×10 9 ) copies/mL and 2.97×10 3 (9.96×10 2 to 3.58×10 8 ) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P =0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group ( P <0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P =0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group ( P =0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P <0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P <0.05) were independent risk factors for BKV infection after HSCT., Conclusion: Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: According to the literature of recent years, there has been an increased interest in non-oncological diseases of the bladder, between which differential diagnostics have to be carried out in order to determine a plan for the diagnosis and treatment of patients with these nosologies. There are often certain difficulties in the differential diagnosis of some forms of viral cystitis and leukoplakia OBJECTIVE: to determine pathomorphological criteria for the differential diagnosis of leukoplakia and chronic recurrent papillomavirus cystitis., Materials and Methods: The prospective study included 85 sexually active patients aged 20-45 years, who were divided into two groups depending on the etiological factor. Patients of group I (n=70) - with chronic recurrent cystitis (CRC) of papillomavirus (PV) etiology, group II (n=15) - with leukoplakia. All patients were examined in accordance with the recommendations of the European Association of Urology (EAU) and the Russian Society of Urology (ROU); an additional endoscopic examination of the bladder (cystoscopy) was performed, followed by a morphological examination of the bladder biopsy., Results: A morphological examination of biopsy tissue in all patients of group I revealed koilocytic transformation of the urothelium combined with non-keratinizing metaplasia of the urothelium, and in patients of group II, in all cases, keratinizing metaplasia of the urothelium with hyperkeratosis was detected., Conclusion: Morphological examination is the gold standard in differential leukoplakia and chronic recurrent papillomavirus cystitis.

We report a case of adenovirus nephritis (ADVN) in a kidney transplant recipient (KTR) occurring within 8 days post-transplantation. The patient, a 35-year-old male, displayed systemic symptoms, high-grade fever, and acute kidney injury (AKI) without signs of hemorrhagic cystitis (HC). Extensive diagnostic workup revealed widespread necrotizing granulomatous inflammation in the allograft, leading to the identification of adenovirus (ADV) via histopathology and polymerase chain reaction (PCR) testing. The source of ADV transmission remained uncertain, raising questions about the potential donor-derived infection. Unlike typical ADVN cases, the patient exhibited no hematuria or urinary symptoms. The case underscores the atypical presentation of ADVN in KTRs, challenging the conventional understanding of its timeline, transmission routes, and associated clinical features. We discuss the diagnostic challenges, histological findings, and management strategies for ADVN, emphasizing the importance of considering this entity in KTRs with unexplained fever and AKI, even in the absence of classical urinary symptoms or hematuria., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: The objective was to assess PD-L1 expression in nonbacterial chronic cystitis (NCC) and bladder cancer (BC)., Methods: The present study included 20 NCC and 20 BC patients. The degree of inflammation of the bladder wall was assessed on slides stained with H&E. Viral pathogens (herpes simplex virus, Epstein-Barr virus, cytomegalovirus, and high-risk HPVs) were detected using real-time polymerase chain reaction analyses of the bladder specimens. Immunohistochemistry was performed to assess the PD-L1 expression in bladder tissue., Results: Expression of PD-L1 was detected in 40% of NCC patients and 85% of BC patients. Viral pathogens were found in 50% of NCC patients and 60% of BC patients, with EBV being the most common. In NCC patients the immune cell score correlated strongly with the degree of inflammatory infiltration of the bladder wall (r = 0.867, p < 0.001), the presence of lymphoid aggregates in the submucosa (r = 0.804, p < 0.001), koilocytosis (r = 0.620, p = 0.004), and the presence of viral pathogens (r = 0.784, p < 0.001). In BC patients the immune cell score correlated with the degree of inflammatory infiltration of the bladder wall (r = 0.534, p = 0.015) and the presence of viral pathogens (r = 0.626, p = 0.003), but not with the presence of lymphoid aggregates in the submucosa (r = 0.083, p = 0.729), and koilocytosis (r = 0.366, p = 0.112)., Conclusions: Expression of PD-L1 was detected in a cohort of NCC patients, although the PD-L1 positivity rate was lower than that in BC. Our results demonstrate that the degree of PD-L1 expression in bladder tissue is associated with the presence of viral infections and with the degree of inflammatory infiltration of the bladder wall in both NCC and BC., (© 2024. The International Urogynecological Association.)

A retrospective cross sectional study was conducted at the Virology Department, Armed Forces Institute of Pathology (AFIP) and Armed Forces Bone Marrow Transplant Centre (AFBMTC), Rawalpindi, from January 2016 to July 2018. Medical records of 193 patients were examined to determine the number of patients developing Haemorrhagic Cystitis associated with BK virus (BKV). BKV PCR testing was done on the patients' urine samples. Cytomegalovirus reactivation was also assessed weekly from day 30 to day 100, by CMV quantitative PCR testing on blood samples. Out of 193 patients, 11 (5.6%) developed haemorrhagic cystitis and all these patients were positive for BKV on urine samples. The maximum number of positive cases, i.e. 5 (2.6%) was in the age group three months to 10 years. Primary disease in seven out of 11 cases was Beta-Thalassemia Major.

Small-molecule drugs inhibiting BK polyomavirus (BKPyV) represent a significant unmet clinical need in view of polyomavirus-associated nephropathy or hemorrhagic cystitis, which complicate 5% to 25% of kidney and hematopoietic cell transplantations. We characterized the inhibitory activity of acitretin on BKPyV replication in primary human renal proximal tubular epithelial cells (RPTECs). Effective inhibitory concentrations of 50% (EC 50 ) and 90% (EC 90 ) were determined in dilution series measuring BKPyV loads, transcripts, and protein expression, using cell proliferation, metabolic activity, and viability to estimate cytotoxic concentrations and selectivity indices (SI). The acitretin EC 50 and EC 90 in RPTECs were 0.64 (SI 50 , 250) and 3.25 μM (SI 90 , 49.2), respectively. Acitretin effectively inhibited BKPyV replication until 72 h postinfection when added 24 h before infection until 12 h after infection, but decreased to <50% at later time points. Acitretin did not interfere with nuclear delivery of BKPyV genomes, but it decreased large T-antigen transcription and protein expression. Acitretin did not inhibit the initial round of BKPyV replication following transfection of full-length viral genomes, but it affected subsequent rounds of reinfection. Acitretin also inhibited BKPyV replication in human urothelial cells and in Vero cells, but not in COS-7 cells constitutively expressing Simian virus 40 (SV40) large T antigen. Retinoic acid agonists (all- trans retinoic acid, 9- cis retinoic acid [9- cis -RA], 13- cis -RA, bexarotene, and tamibarotene) and the RAR/RXR antagonist RO41-5253 also inhibited BKPyV replication, pointing to an as-yet-undefined mechanism. IMPORTANCE Acitretin selectively inhibits BKPyV replication in primary human cell culture models of nephropathy and hemorrhagic cystitis. Since acitretin is an approved drug in clinical use reaching BKPyV-inhibiting concentrations in systemically treated patients, further studies are warranted to provide data for clinical repurposing of retinoids for treatment and prevention of replicative BKPyV-diseases.

Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P < 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.

The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 10 6 (range: 2.8 × 10 1 -1.2 × 10 14 ) and 1.9 × 10 3 copies/mL (range: 3-2.1 × 10 6 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 10 7 (range: 65-1 × 10 11 ) and 2.9 × 10 3 (range: 7-7.8 × 10 4 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC., (© 2020 Wiley Periodicals LLC.)

Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.

The current coronavirus disease 2019 (COVID-19) pandemic is a challenge for physicians in triaging patients in emergency rooms. We found a potentially dangerous overlap of classical urinary symptoms and the as yet not fully described symptoms of COVID-19. After a patient was primarily triaged as a urosepsis case and then subsequently diagnosed with COVID-19, we focused on an increase in urinary frequency as a symptom of COVID-19 and identified this in seven males out of 57 patients currently being treated in our COVID-19 wards. In the absence of any other causes, urinary frequency may be secondary to viral cystitis due to underlying COVID-19 disease. We propose consideration of urinary frequency as an anamnestic tool in patients with infective symptoms to increase awareness among urologists during the current COVID-19 pandemic to prevent fatal implications of misinterpreting urological symptoms., (Copyright © 2020. Published by Elsevier B.V.)

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.

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 10 4 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 10 4 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 10 4 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 10 4 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 10 4 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

We present a patient with virus-associated hemorrhagic cystitis who underwent kidney and allogenic hematopoietic stem cell transplantations (allo-HSCT). Six months post-allo-HSCT, adenovirus hemorrhagic cystitis occurred, which has been in remission after a single dose of intravesical cidofovir. This might cause prolonged neutropenia and nephrotoxicity, suggesting cidofovir absorption in the blood., (© 2019 Wiley Periodicals, Inc.)

Background: BK polyomavirus reactivation can occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may lead to hemorrhagic cystitis (BKPyV-HC). We hypothesized that development of BKPyV-HC is associated with increased mortality post allo-HSCT., Methods: We retrospectively reviewed data on 133 adult patients (≥18 years old) who underwent allo-HSCT from 2007 until 2014 at Hospital Israelita Albert Einstein in São Paulo, Brazil., Results: Thirty-six patients presented with BKPyV-HC after a median time of 42 days, with a 1-year cumulative incidence probability of 28.9% (95% CI 21.5%-36.7%). In a multivariate Cox model, risk factors for development of BKPyV-HC included younger age, male sex, development of grade 2-4 acute graft-versus-host disease and recipients of umbilical cord blood grafts. Development of grade 3-4 BKPyV-HC (but not grade 1-2) was associated with a decreased overall survival (OS) in a multivariate Cox model (hazard ratio [HR] 7.51, P < 0.0001) and an increased risk of TRM (HR 3.66, P < 0.0001). Grade 3-4 BKPyV-HC was also associated with an increased risk of relapse that did not reach statistical significance (HR 3.01, P = 0.07). Median overall survival (OS) post-BKPyV-HC was 4.7 months, and cidofovir had no impact on survival., Conclusion: Development of BKPyV-HC appears to be associated with decreased survival following allo-HSCT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Introduction: The human papilloma virus (HPV) belongs to double-stranded, DNA circular viruses which infect the epithelial cells. The highest incidence of HPV is identified in malignant processes which affect the uterine cervix, as well as vulvar, penile, rectal and pharyngeal regions., Goal of Study: An attempt to find correlations between HPV incidence rates in urine sediment cells and in desquamated epithelial cells of the uterine cervix in a group of patients with frequent, recurrent cystitis., Materials and Methods: HPV presence was studied, both in urine sediment cells and in uterine cervix epithelial cells of 77 patients., Results: An analysis of urinary sediments brought a total of twenty (25.97%) positive and 57 (74.03%) negative results. In turn, an evaluation of uterine cervix material samples revealed 17 (22.08%) positive and 60 (77.92%) negative results., Conclusions: The study enabled a comparison between HPV prevalence rates in urine sediment cells and in uterine cervix epithelial cells of an examined patient. The performed observations are likely to trigger a further analysis of the studied issue; however, the obtained results provide arguments for different natural histories of the infection processes.

Introduction: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical., Methods: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively., Results: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure., Conclusion: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.

In a retrospective case-control study, we aimed to assess the utility of plasma BK viral load value to predict hemorrhagic cystitis (HC) symptoms after allogeneic hematopoietic stem cell transplantation (alloHSCT). During first 100 post-transplantation days of all adult AlloHSCT recipients at the University of Nebraska Medical Center from October 1, 2011, to June 30, 2014, 8 unexcluded cases of HC were identified and matched with 88 unexcluded unaffected control cases. Viral loads were determined for archived DNA extracted from plasma collected within 3 weeks before transplantation until ∼100 days after transplantation. Clinical factors, time of onset of BK viremia, and BK viral load were compared between case and control subjects to identify risks for HC. Symptomatic HC occurred in 8/96 (8.3%) of patients at a median of 34 days after transplantation. BK viremia either before or during symptoms was detected in all 8 (100%) HC patients and in 20/88 (22.7%) of control subjects. BK viremia was detected at a median of 8 days before HC clinical symptoms. The log of first positive viral load was not a statistically significant predictor (P = .17) of symptomatic BK. Median BK viral load peak was significantly higher for 8 patients with HC versus 20 viremic patients without HC (6.66 vs 5.06; P < .052). Further study is required to evaluate the predictive value of the BK viral load for HC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Viral hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) can be devastating. Standard treatment modalities have not been well established, but immune reconstitution may be necessary for sustained viral clearance. We studied five pediatric patients who developed viral HC after haplo-identical HSCT. All patients developed virus-specific CD4- and CD8-positive T cells, and the emergence of these viral-specific T cells was temporally associated with successful viral clearance., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Herpes simplex virus (HSV)-1/2 can still be reactivated after allogeneic haematopoietic stem cell transplantation (allo-HSCT) even when the prophylactic acyclovir is used. However, the risk factors for HSV-1/2 viremia and the clinical outcomes following unmanipulated haploidentical HSCT remain unknown., Objectives and Study Design: Nineteen patients with HSV-1/2 viremia and fifty-seven patients without HSV-1/2 viremia which were selected using the case-pair method after undergoing haploidentical HSCT were enrolled. We analysed the risk factors for HSV-1/2 viremia and compared the clinical outcomes between the two groups., Results: The risk factors for HSV-1/2 viremia included HLA disparity ≥2 loci (p=0.049) and cytomegalovirus (CMV) reactivation (p=0.028). The incidences of platelet engraftment, oral mucositis and severe haemorrhagic cystitis (HC) in patients with and without HSV-1/2 viremia were 77% and 94% (p=0.003), 78% and 13% (p=0.000), and 25% and 6% (p=0.04), respectively. Moreover, the median time to platelet engraftment in patients with and without HSV-1/2 viremia was +25days (range, +11-+80) and +17days (range, +8-+67) (p=0.004), respectively. According to the multivariate analyses, HSV-1/2 viremia was associated with delayed platelet engraftment (p=0.038), a higher incidence of oral mucositis (p=0.000) and severe HC (p=0.038). However, HSV-1/2 viremia was not associated with non-relapse mortality (34.0% vs. 31.5%, p=0.26), leukaemia-free survival (60.9% vs. 57.9%, p=0.46) and overall survival (61.2% vs. 60.7%, p=0.37)., Conclusions: Based on our study results, we recommend that HSV-1/2 PCR should be performed upon clinical suspicion of HSV-1/2 infection., (Copyright © 2017. Published by Elsevier B.V.)

Introduction: Hemorrhagic cystitis (HC) is a well-recognized problem that is regularly observed after hematopoietic stem cell transplantation (HSCT). The published data does not report on the potential risk factors for the viral-induced HC that might require prophylactic treatments., Patients and Methods: We conducted a retrospective analysis of all adult patients who underwent allogeneic HSCT at Jules Bordet Institute between 1992 and 2013. Our institutional protocol consists in monitoring the patient for signs and symptoms of HC on a daily basis during the initial admission for HSCT, then once weekly after discharge until 2 months thereafter., Results: HC was found in 64 patients, of whom 56 (87.5%) had viral-induced HC. The median time between HSCT and HC was 39.5 days (range, 1-2766 days); the median time between detection of a viral infection and HC was 32 days (range, 0-2752 days). In multivariate analysis, HC is correlated to the infection with the BK virus (hazard ratio, 6.0; 95% confidence interval, 5.03-6.90; P = .0001) and the adenovirus (hazard ratio, 4.93; 95% confidence interval, 4.06-5.80; P = .0003). The 5-year overall survival of patients with HC was 36%. The 5-year survival rates were not statistically different between patients with or without HC (25% vs. 39%; P = .20)., Conclusion: The presence of the identified risk factors should prompt closer follow-up with screening tests and preventive measures for BK virus and adenovirus infections in patients undergoing HSCT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical effect and safety of surgical treatment for severe, refractory hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Patients with severe HC, who were admitted to Peking University Institute of Hematology from January 2010 to December 2015, were enrolled in this study.All patients were refractory to medical managements and received bladder surgery including mucous electrocoagulation and/or selective transcatheter arterial embolization. Results: A total of 17 patients with severe HC (grade Ⅲ, n =5; grade Ⅳ, n =12) received surgical treatment, including 11 embolization and 18 mucous electrocoagulation.The median time from allo-HSCT to surgery was 107 d (46-179 d) and 75 d after HC.Eight patients only received embolization.Four patients only received mucous electrocoagulation.Five patients were given combined embolization and electrocoagulation.HC was cured in 11 patients, improved in 1 patient, which corresponded to a response rate of 70.6% and complete remission rate of 64.7%.Five patients didn't respond to these methods.In patients with response, macroscopic hematuria disappeared 3 to 10 days after treatments whereas microscopic hematuria vanished after 25 to 32 days.Both procedures were well tolerated and no severe adverse effects were observed. Conclusion: Surgery of bladder mucous electrocoagulation and/or selective arterial embolization are safe and effective for severe HC.

Background: Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown., Methods: We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality (NRM), GVHD, and healthcare resource use., Results: In total, 94 cases of HC were identified and matched to controls based on age, donor type, disease type, and disease status at transplantation. The total incidence of HC was 17.7% (117 of 661 patients). Cases had a higher rate (43.6% vs 27.1%, P=.0394) of acute GVHD (Grade II-IV), and chronic GVHD requiring systemic steroids (34.9% vs 18.6%, P=.004). Male gender was found to be a risk factor (hazard ratio [HR]=1.725, P=.017). OS and progression-free survival did not differ between cases and controls (OS HR=1.128, 95% confidence interval [CI] 0.7807-1.639; progression-free survival HR=0.8809, 95% CI 0.6320-1.234), however the rate of NRM was higher in cases (HR=1.632, 95% CI 1.007-2.830). Median length of hospitalization was longer for patients with HC than matched controls (65.5 days vs 40.5 days, P<.0001)., Conclusion: HC is common in patients undergoing allogeneic SCT with FluBuATG conditioning, and affects the duration of hospitalization. Rate of GVHD is higher among patients with HC. While OS is not affected, an association was seen with higher NRM in our study. Improvement in treatment for HC may lead to reductions in morbidity and healthcare resource utilization., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BK virus (BKV) hemorrhagic cystitis (HC) is a serious cause of morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT) in patients with hematological malignancies. Around half of allogenic HSCT patients present with BKV viruria at some point after HSCT; about 5-40% of these patients subsequently develop active HC. Supportive care including bladder irrigation, blood transfusions and symptomatic pain management remains the mainstay of therapy; the acyclic nucleoside analogue cidofovir is currently the front-line drug for BKV-HC treatment. Here we report the first case of severe hemorrhagic cystitis from India who was successfully treated with low dose cidofovir therapy., (© Journal of the Association of Physicians of India 2011.)

To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study investigated the significance of urological surgical intervention for viral hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 1, 024 patients underwent allo-HSCT at our medical center between January 2006 and July 2014. In the 6 patients (0.58%) who required urological surgical treatment for viral HC, we retrospectively analyzed patient characteristics and outcomes. Two patients underwent nephrostomy for bilateral hydronephrosis due to bladder tamponade. One of these patients showed no improvement in renal function, graft versus host disease worsened and he died on postoperative day (POD) 5. The other patient displayed improved renal function but hematuria did not improve, and total cystectomy was required. To control bleeding, we performed transurethral electrocoagulation (TUC) on 3 patients, and total cystectomy was performed on 2 patients. All 3 patients who underwent TUC had BK virus HC. Two of these patients experienced marked improvement in hematuria from immediately after surgery. Hemostasis was only temporary in the other patient, who eventually died due to septicemia on POD 24. The 2 patients who underwent total cystectomy had adenovirus HC. Both experienced secondary hemorrhage postoperatively and required further surgery. Eventually, one died due to postoperative bleeding on POD 1, and one died due to postoperative pneumonia on POD 57. Urological surgical treatment for HC was effective in some cases, but the ultimate outcome greatly depends on the general condition of the patient and treatment of the underlying hematological disorder. TUC may be considered for HC (particularly BK virus HC), but total cystectomy (especially inaden ovirus HC) should be avoided.

Purpose: BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation., Methods: We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period., Results: The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor., Conclusions: Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.

Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad-spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2-5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients and polyomavirus-associated nephritis in renal transplant patients, while JC polyomavirus (JCPyV) can generate progressive multifocal leukoencephalopathy in immunocompromised individuals. Since 2007, additional human polyomaviruses (HPyVs) have been identified. In this study, we examined the urines of allo-HSCT patients for possible presence of polyomaviruses BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and HPyV10 (MWPyV)., Methods: A total of 185 urinary samples obtained 2002-2007 from 105 allo-HSCT patients, 32/105 with HC, were tested for the above-listed HPyVs by a bead-based multiplex assay. Of these, 142 urine samples had previously been tested for BKPyV and JCPyV by nested polymerase chain reaction (PCR)., Results: Aside from BKPyV and JCPyV, which dominated, HPyV7 was detected in 5 BKPyV-positive urinary samples from 1 patient. The multiplex assay was more sensitive and specific than the nested PCR. BKPyV and/or JCPyV were found in all but 1 of the previously BKPyV- or JCPyV-positive samples, although 6 previously BKPyV-positive cases were now JCPyV-positive or the reverse. Furthermore, 18/79 previously negative samples were found to be BKPyV and/or JCPyV positive, and a total of 21 double infections were found. Lastly, in 1/29 HC patients, only JCPyV was detected., Conclusion: HPyV7 was found for the first time in urine of an allo-HSCT patient, and BKPyV and JCPyV were more commonly found in urine samples using the bead-based assay compared to testing by nested PCR. Finally, only JCPyV was detected in the urine of 1 HC patient., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BK polyomavirus (BKPyV) commonly reactivates after kidney transplantation, and can cause polyomavirus-associated nephropathy (PyVAN), whereas after allogeneic stem cell transplantation the most frequent manifestation of BKPyV is polyomavirus-associated hemorrhagic cystitis (PyVHC). Despite high-level BKPyV replication in both, the pathogenesis and manifestation of both BKPyV entities appears to differ substantially. We describe an unusual case of simultaneous PyVAN and PyVHC presenting with acute symptoms in a BKPyV-IgG positive recipient eight months after kidney transplantation from a haploidentical living donor, who was BKPyV-IgG negative. Symptoms of cystitis and viremia subsided rapidly after reduction of immunosuppression., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

BK virus (BKV) is associated with kidney and bladder disease after hematopoietic cell transplantation (HCT) but less is known about the seroprevalence of pre-transplant antibodies to BKV in children. We measured BKV IgG antibody titers in 36 children before HCT. BKV IgG antibodies were detected in all 36 patients, with 28/36 (77.8%) developing BK viremia in the first 100 days. Pre-HCT BKV IgG antibody titers >1:40,960 were protective against later BK viremia ≥10,000 copies/ml. The seroprevalence of antibodies to BKV is high in children undergoing HCT and post-transplant BK viremia, which is associated with bladder and kidney injury, is common., (© 2015 Wiley Periodicals, Inc.)

Background: Hemorrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in pediatric HSCT patients., Methods: Ninety pediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus (ADV) and BK virus (BKV) by quantitative real-time polymerase chain reaction in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% confidence interval) for BKV ≥1 × 10(9) copies/mL of urine was 7.39 (1.52, 35.99), with a P-value of 0.013. Those with acute graft-versus-host disease (aGVHD) also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 10(9) copies/mL., Results: BK viremia did not reach significance as a risk factor for development of HC (P = 0.06). Only 8 patients showed ADV viruria and 7 showed ADV viremia; all had low viral loads and 4 had no evidence of HC., Conclusion: HC in pediatric HSCT is correlated most strongly to elevated urinary viral load of BKV and to aGVHD, but less strongly to BK viremia., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Viral infections are an important complication of transplantation. Polyomavirus are the commonest viruses that infect the renal allograft. Herpes virus nephropathy has also been described. In the past 15 years, adenovirus nephritis has emerged as a potentially life-threatening disease in renal transplant patients in developed countries. Most of the papers devoted to adenovirus nephritis are reported cases. The fate of such patients in resources-limited countries is not known. Herein, we describe the clinical, biological and prognostic findings of a black African transplanted patient with adenoviral hemorrhagic cystitis. This case is the very first of its kind reported in black Africa in a setting of a start of a renal transplantation pilot project. The patient is a 54-year-old man admitted at the nephrology service for gross haematuria and fever occurred 1 month after kidney transplantation. The diagnosis of adenoviral hemorrhagic cystitis has been suspected because the patient has displayed recurrent conjunctivitis and gastroenteritis well before transplantation, which was then confirmed by the real-time polymerase chain reaction performed on the blood. Conservatory measures associated with immunosuppression reduction have permitted the discontinuation of haematuria. This case has been discussed in regard of the epidemiology, the diagnosis, the treatment, the evolution and the prognosis of the adenoviral infection in the renal transplant patient. A review of the literature has been performed subsequently., (Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Background/aims: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses., Methods: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade., Results: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment., Conclusions: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10(10) copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

Leflunomide, an immunosuppressant with antiviral activity, was used to treat 5 children with severe BK virus-associated hemorrhagic cystitis after hematopoietic stem cell transplantation. Without severe side effects, BK viral loads in blood and urine decreased significantly after leflunomide treatment. Compared with 7 historical controls, duration of BK virus-associated hemorrhagic cystitis was significantly shorter in patients receiving leflunomide therapy (P < 0.01).

A 61-year-old man with multiple myeloma (IgG-κ) received autologous peripheral blood stem cell transplantation (PBSCT) after induction of VAD in July 2009, and obtained a very good partial response. In November 2009, he was admitted to our hospital because of adenovirus-induced hemorrhagic cystitis and pneumocystis jiroveci pneumonia. The pneumonia resolved with sulfamethoxazole and steroid pulse therapy, and cystitis subsided spontaneously. In December 2009, serum protein electrophoresis showed two abnormal protein bands (APB)(IgG-λ, IgA-λ), different from the original M-protein, and IgG thereafter increased to 2,771 mg/dl with a concomitant increase in anti-adenovirus antibody to 4,096. In October 2010, APB disappeared. To date, he has been in stable complete remission for five years since PBSCT. The emergence of APB is considered to be a surrogate marker for long-term remission. Immune reconstitution syndrome and APB after high dose chemotherapy following PBSCT are discussed herein.