Does Polyoma (BK) Virus Contribute to Development of Hemorrhagic Cystitis (HC) in Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation (UD HSCT) Recipients? A Prospective Evaluation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5282-5282
Author(s):  
Poliana A. Patah ◽  
Nicholas A. Szewczyk ◽  
Lisa Gilman ◽  
Alison Gulbis ◽  
Joyce Neumann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hemorrhagic Cystitis ◽  
Bk Virus ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Grade 3 ◽  
Hodgkin's Lymphomas

Abstract BK virus infection is highly prevalent in humans, and has been associated with development of HC after HSCT. Previously we determined that UD HSCT is independently associated with higher prevalence of HC (El-Zimaity et al. Blood 2004). In order to further investigate the association of BK with HC, we hypothesized that patients who have positive urine PCR for BK virus before UD transplant have a higher incidence of HC. Methods: we studied 62 consecutive patients transplanted from 09/05 to 05/06. Preparative regimens were ablative (n=26) or reduced intensity (n=36); 15 patients (23%) received cyclophosphamide-containing regimens. GVHD prophylaxis was tacrolimus and mini-methotrexate. Stem cell source was bone marrow (n=28), peripheral blood (n=25) or umbilical cord (n=9). BK virus quantitative PCR was performed on urine samples collected upon admission. Results: Median age was 53 years (range, 19–67). Diagnoses were leukemias (n=36), multiple myeloma (n=2), Hodgkin’s disease (n=4), non-Hodgkin’s lymphomas (n=16), and other (n=4). Median time to platelet engraftment was 16 days (range, 0–62; n=51). Median follow-up is 97 days. BK PCR was positive in 28 patients (45%). Number of viral copies ranged from 300 to > 200 million copies. Eleven patients (18%) developed HC, at a median of 25 days after HSCT. HC was of grade 1 (n=1), grade 2 (n=4), grade 3 (n=5), grade 4 (n=1; required bilateral nephrostomies). In the PCR positive group, 7 patients (25%) had HC, versus 4 (12%) in the PCR-negative group (hazard ratio = 3.4 for a positive PCR; log-rank p = 0.057). 100-day cumulative incidence of HC is shown in the figure. 45% of CB recipients developed HC. Incidence of HC was not statistically significantly increased among recipients of ablative or cyclophosphamide-containing regimens. Likewise, development of grade II-IV acute GVHD (n=18, 29%) was not associated with higher rates of HC. Six patients developed HC before platelet engraftment. Viral load did not correlate with development of HC. Four patients had viruria of 50–200million/mL; only one developed HC. Conclusion: BK viruria pre-HSCT may be a risk factor for development of HC; further study is needed in a large cohort of patients. Figure Figure

scholarly journals Outcome of Severe Aplastic Anemia Post Allogenic Stem Cell Transplant with Mycophenolate and Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4879-4879
Author(s):  
Omar Albanyan ◽  
Hyejeong Jang ◽  
Seongho Kim ◽  
Andrew Kin ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

Hemorrhagic Cystitis and BK Virus Infection in Children after Hematopoietic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2195-2195
Author(s):  
Bernd Gruhn ◽  
Loreen Maier ◽  
Renate Egerer ◽  
Dietlinde Fuchs ◽  
Felix Zintl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Virus Infection ◽  
Hemorrhagic Cystitis ◽  
Bk Virus ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Virus Load ◽  
Graft Versus Host

Abstract Hemorrhagic cystitis (HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). The pathogenesis of HC in adults is not fully understood and may be influenced by BK virus infection, type of transplant, conditioning regimen, stem cell source, and graft-versus-host disease. Little is known about the development of HC in children after HCST, especially about the association with BK virus infection. Therefore, we retrospectively analyzed the incidence, risk factors and BK virus association of HC in 165 consecutive children (median age, 12 years) who underwent peripheral blood stem cell (n=97; T-cell depleted: n=48) or bone marrow transplantation (n=68) between 1/2000 and 12/2006 in a single center. Fifty nine patients received autologous HSCT and 106 patients underwent allogeneic HSCT. Nineteen of the 165 patients (11.5%) developed HC after a median of 33 days (range, 1–98 days). All 19 patients with HC underwent allogeneic HSCT and showed BK viruria after transplantation. An acute graft-versus-host disease was significantly more frequent in children with HC (P < .001). Significant risk factors in univariate binary logistic analyses were age > 12 years (OR, 3.275; P < .031), use of busulfan (OR, 3.514; P < .013), use of busulfan and cyclophosphamide in combination (OR, 4.935; P < .002), and an unrelated donor (OR, 3.309; P < .043). Independent risk factors in multivariate binary logistic analyses were age > 12 years and the combination of busulfan and cyclophosphamide. We suggest that cyclophosphamide is toxic to the urinary bladder and busulfan enhances this effect. Furthermore, we analyzed the BK virus load in urine by real-time polymerase chain reaction. We found in patients without HC a significantly increased number of BK virus copies in urine in children older than 12 years (P < .009) and in children who received antithymocyte globulin (P < .001). In addition, BK virus load in urine was significantly increased in children who suffered from HC. Thirteen of 14 children with HC had a BK virus load in urine >107 copies/mL (P < .001). We observed in individual BK virus profiles an increase of BK virus copies in urine before the onset of HC. We conclude that HC in children is a disease of multiple etiologies. Allogeneic HSCT, the combination of busulfan and cyclophosphamide, age > 12 years, and an unrelated donor are risk factors for the development of HC in childhood. Increased BK virus load in urine of more than 107 copies/mL may lead to HC. Therefore, it is useful to quantify BK virus in urine in those children with above mentioned risk factors to initiate early treatment or to prevent the development of HC.

scholarly journals Investigating Antibiotic Exposure and Risk of Severe Acute Graft Versus Host Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4539-4539
Author(s):  
Razan Mohty ◽  
Remy Dulery ◽  
Giorgia Battipaglia ◽  
Eolia Brissot ◽  
Clemence Mediavilla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Exposure Group ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Grade 3 ◽  
Severe Grade ◽  
Neutrophil Engraftment

Several studies have shown that alteration of the microbiota, particularly in the gastrointestinal tract, can be associated with graft-versus-host disease (GvHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) usually get exposed to antibiotics (ATB), mainly in the peri-transplant period. Moreover, ATB, specifically those that target anaerobic bacteria, can alter the microbiota in a variety of body organs. This, in turn, renders several organs vulnerable to injury making them more prone to developing diseases such as GvHD. In this study, we evaluate whether the use of ATB, characterized by duration, timing and type, in the peri-transplant period, is associated with an increased incidence of acute GvHD (aGvHD) and aGvHD-related mortality. In this retrospective study, we included 318 consecutive patients who underwent allo-SCT including haploidentical and cord blood transplantation between December 2012 and June 2018 at a single center. ATB exposure was collected and classified into 3 groups according to the date of initiation of ATB: from the start of conditioning to day - 1 of allo-SCT (early ATB exposure), from day 0 to neutrophil engraftment (late ATB exposure) and a third group of patients who did not receive ATB (no ATB exposure). ATB were only initiated if a patient develop fever or show signs of infection. Patients did not receive any prophylactic ATB. Exposure was further categorized as primary or adjunct. Primary exposure included the use of 4 classes of ATB: carbapenems, anti-pseudomonal penicillin, 4thand 5thgeneration cephalosporins and fluoroquinolones. Adjunct ATB comprised other ATB and was further divided into 2 groups according to anaerobic coverage. The median age at transplant was 55 years. The stem cell source was peripheral blood in 85%, bone marrow in 10% and cord blood in 5% of the patients. Ninety-nine percent of the patients received cyclosporine A as GvHD prophylaxis and 80% and 7% of the patients received (along with cyclosporine A), mycophenolate mofetil and methotrexate, respectively. In addition, 35% and 89% of the patients received post-transplant cyclophosphamide and anti-thymocyte globulin, respectively, as GvHD prophylaxis. The median time to neutrophil engraftment was 16 days post-transplant. The median follow-up was 85 months. 93.7% of the patients received ATB in the peri-transplant period with 64.5% of them in the early ATB exposure group, and 29.2% of them in the late ATB exposure group. The 2-year overall survival and progression free survival were 74.3% and 63.6% in patients with early ATB exposure, compared to 79.5% and 70.8% in patients with late ATB exposure (p=0.11 and p=0.07 respectively). The 2-year cumulative incidence of non-relapse mortality was 16.5% in patients with early ATB exposure, compared to 15.1% in patients with late ATB exposure (p=0.63). The 180-days cumulative incidence of grade 2-4 and 3-4 aGvHD were 23.8% and 12.2% in patients with early ATB exposure, compared to 27.2% and 5.4% in patients with late ATB exposure (p=0.64 and p=0.06 respectively). In multivariate analysis, including the most important parameters associated with GvHD (stem cell source and donors, conditioning regimen, sex mismatch and patients age), early ATB initiation was the only parameter associated with a significantly higher risk of severe grade 3-4 aGvHD [HR 0.51 (0.28-0.90); p=0.02]. In conclusion, in the absence of any ATB prophylaxis, early initiation of ATB, before graft infusion,is associated with a significantly higher risk of severe grade 3-4 aGvHD. Weighing risk of morbidity and mortality associated with infections versus later on risk of developing aGvHD is essential. Hence, new strategies should be developed to risk stratify patients with fever and thus to avoid early non necessary ATB exposure especially in those who develop fever during anti-thymocyte globulin infusion. Studies evaluating such strategies will be necessary in the next years. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding. Malard:Astellas: Honoraria; JAZZ pharmaceutical: Honoraria; Sanofi: Honoraria; Keocyte: Honoraria; Janssen: Honoraria; Therakos/Mallinckrodt: Honoraria.

Symptomatic Improvement Following Intravesicular Cidofovir for the Management of BK Virus Associated Cystitis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3007-3007 ◽  
Author(s):  
Larry W. Buie ◽  
Kamakshi V. Rao ◽  
Stacy Epstein ◽  
Thomas C. Shea ◽  
Terrence Comeau ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Transplant ◽  
Hemorrhagic Cystitis ◽  
Bk Virus ◽  
High Dose ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Viral Loads

Abstract BACKGROUND: Hemorrhagic cystitis (HC) is a complication of hematopoietic stem cell transplantation, occurring in 10 to 70% of transplant recipients. Factors that may contribute to the risk of developing HC include intensive preparative regimens, especially those including busulfan, high-dose cyclophosphamide or ifosfamide, transplantation from matched unrelated donors, infection with adenovirus, and the development of graft-versus-host disease. The reactivation of latent BK virus in the kidney is thought to lead to the development of late-onset HC in hematopoietic stem cell transplant patients. Early reports of cidofovir’s efficacy in BK virus-associated HC used intravenous cidofovir, but treatment was often complicated or compromised by excessive toxicity, especially renal compromise. Based on small single patient reports of the use of intravesicular cidofovir in the management of other viral causes of cystitis, we evaluated the use of intravesicular cidofovir for the management of BK virus associated cystitis. METHODS: In patients undergoing stem cell transplant, BK viral loads were routinely monitored twice weekly. The presence of cystitis or hematuria in a patient with detectable BK viruria was considered the trigger for initiation of therapy. Patients were treated with cidofovir at a dose of 5 mg/kg. Drug was diluted with 60mL of normal saline and administered via foley catheter, which was clamped for one hour post administration. Weekly repeat dosing was allowed as long as symptoms persisted. In addition to symptom control, BK viral loads were measured before, during, and after treatment. RESULTS: Four patients were included in this initial evaluation. All were recipients of allogeneic stem cell transplants; three were recipients of matched unrelated donor transplants and one received a transplant from a matched sibling. Patients received between 1 and 4 doses of cidofovir for initial therapy. All 4 patients experienced complete resolution of symptoms. The range for symptom resolution ranged from 2 days to 3 weeks. Symptoms reappeared in only 1 patient after discontinuation of therapy. Monitoring of BK urine viral loads revealed that 3 of the 4 patients had a greater than 50% decrease in urine BK viral load with initial dosing of cidofovir, indicating presence of antiviral activity when the drug is administered by this novel route. CONCLUSION: Intravesicular cidofovir is safe, easy to administer, and associated with both elimination of symptoms and reduction in viral loads in patients with hemorrhagic cystitis following high dose therapy and allogeneic transplantation.

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4674-4680 ◽  
Author(s):  
Maha El-Zimaity ◽  
Rima Saliba ◽  
Kawah Chan ◽  
Munir Shahjahan ◽  
Antonio Carrasco ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hemorrhagic Cystitis ◽  
Lymphocytic Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Blood And Marrow Transplantation ◽  
Stem Cell Source ◽  
Donor Type ◽  
Total Body ◽  
Unrelated Cord Blood

Abstract Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. (Blood. 2004;103:4674-4680)

scholarly journals BK virus-associated hemorrhagıc cystitis in patients wıth allogeneıc hematopoıetıc cell transplantation: report of three cases

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Immunosuppressive Treatment ◽  
Active Agent ◽  
Bk Virus ◽  
Cell Transplant ◽  
Hematopoietic Stem

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

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