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.

BKV Disease during the First 100 Days after Allogeneic Hematopoietic Stem Cell Transplantation - Results of a Screening Program and Retrospective Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3403-3403 ◽  
Author(s):  
Philip Posdzich ◽  
Marco Herling ◽  
Silke Leitzke ◽  
Laura Hamacher ◽  
Veronica Di Christanziano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Acute Gvhd ◽  
Screening Program ◽  
Hemorrhagic Cystitis ◽  
Bk Virus ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract BK virus (BKV) is a human polyomavirus often acquired in childhood which can reactivate after allogeneic hematopoietic stem cell transplantation (HSCT). BKV reactivation may present indifferent ways from asymptomatic viruria to hemorrhagic cystitis or nephritis. Methods We evaluated 377 patients (159 male, 218 female, median age 52 years) who were transplanted at the University of Cologne between 2008 and 2013 to assess incidence and risk factors for BKV disease after allogeneic HSCT. All 377 patients were screened routinely for BKV in urine and serum. We defined BKV disease as hemorrhagic cystitis (HC) with BK virus >100.000/ml in urine, hematuria (2+ until 4+ in dipstick test) and negative urine microbiology. To find risk factors for BKV disease, the impact of conditioning, CMV status, graft-versus-host disease (GvHD), underlying disease, donor mismatch and stem cell source was analyzed. Results According to our definition, BKV cystitis occurred in 37 of 377 patients (9,8%) in the first 100 days after HSCT. In 14 of these 37 patients (37,8%) BKV was also detected in serum. BKV was detected in the urine of 194 patients (51,4%) at any time during the screening program, but only 19,1% developed hemorrhagic cystitis. Sixty-two percent of patients suffering from BKV disease were female, 37,8% male. BKV disease was diagnosed in 13,3% of patients not in complete remission as opposed to 5,4 % of patients in complete remission prior to conditioning (p = 0,010). BKV disease was less common in matched related or unrelated (7,7%) as compared to mismatched or haplo-identical donors (16,7%; p=0,012). Acute GvHD grade II to IV was described in 122 of 377 patients (32,36%). Of them, 13,9% suffered from BKV cystitis in comparison to 7,84% with no or grade I acute GvHD, which did not reach statistical significance. We could not detect any correlation between BKV disease and administration of cyclophosphamide, total body irradiation or anti-thymocyte globuline. There was no association with the graft source. BKV disease was no predictor for non-relapse mortality, overall and relapse-free survival. Conclusion BKV disease is a common complication after allogeneic HSCT. The virus can be found in the urine of about half of our transplanted patients, but only a small proportion developed an HC. State of remission before conditioning and donor mismatch are associated with the development of BKV disease, which had no impact on survival in our cohort. Disclosures Scheid: Novartis: Other: funding outside this work; Celgene: Other: funding outside this work; Janssen: Other: funding outside this work.

Higher Rate of Thrombotic Thrombocytopenic Pupura (TTP) Associated with Graft Versus Host Disease (GVHD) and Unrelated Donor Bone Marrow Transplantation (BMT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1111-1111
Author(s):  
B. Oran ◽  
A. Aleman ◽  
E. J. Shpall ◽  
C. Hosing ◽  
M. Korbling ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Stem Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Lymphoid Malignancies ◽  
Gvhd Prophylaxis

Abstract TTP is one of the complications of allogeneic hematopoietic stem cell transplantation (HSCT). In contrast to idiopathic cases, post-transplantation TTP may not be associated with severe von Willebrand factor-cleaving protease deficiency but rather a diffuse endothelial injury. Our aim was to define incidence, risk factors and mortality of TTP following allogeneic HSCT. 1312 patients with lymphoid malignancies (n=605), myeloid malignancies (n=688) or aplastic anemia (AA, n=18) who were treated with ablative preparative regimens (n=614) or reduced intensity regimens (n=697) followed by HSCT from an HLA matched related (MRD, n=694) or unrelated donor (MUD; n=461) and 1–3 antigen mismatched related (MMR, n=99) or unrelated donor (MMUD, n=57) between December 1997 and December 2004 were studied. Patients with prior allogeneic HSCT or graft failure were excluded. GVHD prophylaxis was tacrolimus-based in 1276 (97.3%) and cyclosporine based in 15 (1.1%) patients. Twenty patients did not receive GVHD prophylaxis per protocol. Anti-thymocyte-globulin (ATG) was added in 350 patients. Stem cell sources were bone marrow (n=626), peripheral blood (n=635) or cord blood (n=50). The following variables were evaluated: age, gender, primary diagnosis, disease status before HSCT, intensity of preparative regimen, stem cell source and acute GVHD(aGVHD) grade ≥2 (time dependent variable). Of the 1312 patients with a median follow-up from transplantation of 11.4 months (range, 5 days-7.2 years), 77 developed TTP (6%). The actuarial risk of developing TTP was 6.5% at 1 year. The median time of the onset of TTP was 67 days post HSCT (range, 11–1812) with 27 cases (35%) presenting after day 100. Female gender, lymphoid malignancies, unrelated or antigen mismatched related donor and aGVHD grade ≥2 were found to be independent risk factors. (Table1). Among the patients who had aGVHD grade≥2, the median time of interval between the onsets of two events was 25 days (range, 2–335 days). All patients were treated with therapeutic plasma exchange (PE). Of the 77 patients only 1 died of TTP (intracranial hemorrhage). The overall one-year survival after TTP was 29% and the most common cause of death were acute or chronic GVHD (n=35, 55%) and primary disease progression (n=10, 16%). Stem cell donors other than MRD, lymphoid malignancies and aGVHD≥2 have been established as risk factors associated with development of TTP and therapeutic PE has been shown to decrease TTP related mortality. Risk factors for TTP after allogeneic HSCT Variables sample size events HR 95% CI p Male 793 33 1.0 Female 518 44 2.2 1.3–3.6 0.002 Myleoid malignancy 688 33 1.0 Lymphoid malignancy 605 42 1.9 1.1–3.3 0.03 AA 18 2 1.3 0.2–8.0 0.75 MRD 694 28 1.0 MUD 461 40 2.9 1.6–5.1 <0.001 MMR 99 7 2.4 0.9–6.0 0.06 MMUD 57 2 1.7 0.4–7.6 0.5 aGVHD ≥2 370 39 3.3 2.0–5.5 <0.001

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

Retrospective Analysis of Hemorrhagic Cystitis After Unrelated Donor Hematopoietic Stem Cell Transplantation In a Chinese Population.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4546-4546
Author(s):  
Jing Jing ◽  
Kangni Wu ◽  
Yi Luo ◽  
Jimin Shi ◽  
Yamin Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Incidence Risk ◽  
Conditioning Regimens

Abstract Abstract 4546 Hemorrhagic cystitis (HC), occurring mostly within first month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), is a common complication which often requires prolonged hospitalization, considerable expense, and occasionally causes significant morbidity. The data from different transplantation centers about this complication are different in the incidence, risk factors, therapeatic strategies and outcome. In this study, we retrospectively analyzed the incidence, risk factors, prophylaxis and treatment regimens of HC after unrelated donor HSCT(URD-HSCT)in our center From October 2000 to February 2008, 168 consecutive patients underwent URD-HSCT were enrolled,including 113 male patients and 55 female patients. The median age was 26 years (range,8-52 years). The main myeloablative conditioning regimens used were busulfan/cyclophosphamide (BuCy) without total body irradiation (TBI); Reduced-intensity conditioning regimens (RIC) were predominantly fludarabine-based combinations without irradiation. Anti-thymocyte globulin(ATG) were added to the conditioning regimen in the patients receiving HLA-mismatched URD-HSCT. The prophylaxis regimen for HC included intravenous mesna,hyperhydration and intermittent diuretic. The diagnosis of HC was based on the presence of sustained microscopic or macroscopic hematuria in the absence of other clinical conditions such as urinary bacteria and fungi infection. It could be clinically graded to I to IV according to hematuria and divided into early onset (EOHC) and delayed (LOHC) according to the time of onset. In total, 27 of 168 patients (16.1%) developed HC at a median interval of 40 days post engraftment (range, 8–89 days). Among them,11 patients developed grade I (6.5%), 10 patients developed grade II (6.0%), 6 patients developed grade III (3.6%), while no patients with grade IV. Five patients(2.98%) presented EOHC and 22 patients (13.17%) presented LOHC. We discovered that in 27 patients with HC only 3 were female (11.1%), however in 141 patients without HC, 52(36.9%) were female (P<0.05). Patients with HC had a higher incidence of acute graft-versus-host disease (aGVHD) (92.6% vs 47.5%, P<0.001) and grades II-IV aGVHD (P<0.001), which is consist with previous reports. Furthermore, 16 patients (59.3%) with HC were ≥30-year-old, 50 patients (35.5%) without HC, were ≥30-year-old (P<0.05). Multivariate analysis showed that primary disease type, donor 's gender or age, stem cell source, myeloablative or nonmyeloablative conditioning regimen, HLA or ABO blood mismatching, the existence of CMV seropositivity were not significantly associated with the risk of HC. All patients achieved excellent response after being treated with alkalinization of the urine, hyperhydration with intravenous fluid. Several patients also received urethral catheterization to bladder washout. No patient died of HC. In conclusion, our results demonstrated that recipient 's gender, aGVHD and recipient's age(≥30-year-old), were three risk factors associated with HC. Other risk factors which had been reported to be related to HC in literatures did not show significant impact in our study. Although effective prophylaxis has significantly decreased the incidence of HC, up to date, the precise pathogenesis of HC has not been well elucidated. More clinical and mechanisms researches should to be explored. Disclosures: No relevant conflicts of interest to declare.

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.

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