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PubMed2000

Sequential vidarabine infusion in the treatment of polyoma virus-associated acute haemorrhagic cystitis late after allogeneic bone marrow transplantation.

Late onset haemorrhagic cystitis (HC) occurs in 20-30% of allogeneic bone marrow transplant patients. Human polyomavirus BK (BKV) (or less frequently adenovirus) may be involved in the pathogenesis of viral HC and can represent a serious post-transplant complication. Diagnosis and treatment of viral HC can be difficult and has an uncertain outcome. We report the efficacy of sequential vidarabine in the treatment of a patient with severe BKV-associated HC, despite the delay in implementing therapy. Bone Marrow Transplantation (2000) 25, 319-320.

Acute Disease↗
PubMed2000

Successful ribavirin therapy for severe adenovirus hemorrhagic cystitis after allogeneic marrow transplant from close HLA donors rather than distant donors.

Intravenous ribavirin was given to nine patients who had developed severe adenovirus-induced hemorrhagic cystitis (AD-HC) which was resistant to conventional therapy or where there was involvement of other organs after allogeneic BMT. Three patients recovered completely from AD-HC, two of whom had been resistant to vidarabine. All three had received sibling BMTs (2 HLA matched, 1 HLA mismatched). Five patients who received BMTs from related (2 HLA mismatched) or unrelated (1 HLA matched, 2 HLA mismatched) showed an improvement in symptoms but had recurrent AD-HC after discontinuation of ribavirin. Improvement in clinical symptoms and termination of virus excretion were well correlated. The last patient who received a mismatched unrelated BMT died during ribavirin therapy. Ribavirin was notably more effective among patients receiving BMTs from siblings in contrast to patients receiving BMTs from alternative donors (<0.05). One patient experienced severe pancytopenia during the second treatment with ribavirin after HC recurrence and recovered after ceasing ribavirin. Thus, ribavirin seems to be very effective for severe AD-HC for some recipients who receive transplants from a genetically close donor. Bone Marrow Transplantation (2000) 25, 545-548.

Adenoviridae Infections↗
PubMed2000

Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir.

Hemorrhagic cystitis (HC) is a common complication following high-dose chemotherapy and bone marrow transplantation, and the treatment of virus-associated HC remains to be optimized. This is the first report on the successful use of cidofovir in a patient with HC and polyoma viruria concomitant with CMV reactivation after allogeneic BMT. Treatment led to a significant decrease in viruria and to sustained suppression of CMV reactivation. Administered with probenecid and hydration, cidofovir was well tolerated, and there were no side-effects.

Antiviral Agents↗
PubMed2000

Intra-muscular vidarabine therapy for polyomavirus-associated hemorrhagic cystitis following allogeneic hemopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication following hemopoietic stem cell transplantation (HSCT), its incidence ranging from 7 to 52% of all patients. Late occurring HC frequently results from viral infections. We describe a patient who developed severe polyomavirus-associated HC, which responded dramatically to a single dose of intra-muscular vidarabine. Previous studies show an improvement in HC with vidarabine therapy, but to date only the intravenous route of administration has been described and responses described take from several days to weeks. This report confirms the safety and efficacy of vidarabine administered intramuscularly when used in patients with an adequate platelet count, thereby making its use feasible when intravenous vidarabine is not available.

Adolescent↗
PubMed2001

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.

Bone Marrow Transplantation↗
PubMed2001

CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation.

Hemorrhagic cystitis (HC) is a known complication of stem cell transplantation. In contrast to early-onset HC that is usually attributed to cyclophosphamide and occurs within a few days of infusion, late onset HC is associated with viral infection. In recent years BK virus has emerged as an important causative agent. We describe two patients who developed late onset HC (38 and 92 days post transplant) associated with BK viruria concomitant with CMV reactivation and suggest a possible role of CMV in the process of BK virus DNA replication.

BK Virus↗
PubMed2002

Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation.

Haemorrhagic cystitis (HC) is an important complication after bone marrow transplantation (BMT). Overt HC (grade > or =2, gross haematuria, clot retention and impairment of renal function), clinically more important than mild and occult HC (grade 1, microscopic haematuria), leads to substantial morbidity and occasional mortality. We retrospectively analyzed 32 cases of clinically overt HC from a series of 236 BMT patients. Significant risk factors included the use of busulphan during conditioning, allogeneic BMT and acute GVHD. Logistic regression showed GVHD to be the most important risk factor. According to the time of engraftment, HC could be divided into pre- and post-engraftment subtypes. Pre-engraftment HC was brief, not more severe than grade 2, and subsided with supportive treatment. In contrast, post-engraftment HC was protracted, often of grade > or =3, associated with severe GVHD, and required surgical intervention in many cases. Polyoma BK viruria, but not adenoviruria, could be demonstrated in both types of HC. The increased severity and association with GVHD of post-engraftment HC suggested that attack of urothelium by immunocompetent cells, possibly directed against BK viral antigens, might play a pathogenetic role.

Adenoviridae↗
PubMed2003

Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries.

Hemorrhagic cystitis (HC) is a common and sometimes life-threatening complication of hemopoietic cell transplantation (HCT) occurring in 7-52% of transplant recipients. In this setting it is usually either related to the use of cyclophosphamide or to a viral infection (BK, JC viruses and adenovirus type 11). Treatment is based on hyperhydration, platelet and blood-cell transfusions, bladder irrigation and pain management. Where these measures have failed to control HC, numerous therapeutic approaches including surgery have been tried with poor success. We report two HCT patients with severe HC successfully treated with selective embolization of the vesical arteries.

Adult↗
PubMed2003

Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation.

To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533-17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584-7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055-9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642-6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847-19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477-19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i). high-dose BU as well as CY is a cause of HC, (ii). protective bladder irrigation has an opposite effect, and (iii). Mesna possibly has a toxic effect on bladder mucosa.

Adolescent↗
PubMed2003

Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology-bone marrow transplantation group.

The purpose of this multicenter study was to assess the incidence and the treatment of hemorrhagic cystitis (HC) in 1218 pediatric patients, with a mean age of 10.8 years, who underwent hematopoietic stem cell transplantation (HSCT). In all, 44 patients (3.6%) developed HC a median 23 days after HSCT. The incidence of HC was higher in allogeneic than in autologous HSCT recipients (P=0.0001). Of the 44 patients, 37 (84%) recovered from HC in a median 30 days (range 3-100); the other seven children died while still suffering from HC. Hyperbaric oxygen therapy (HOT) achieved significantly better results than prostaglandin therapy (P=0.02) in the treatment of grade II-III HC. By multivariate analysis, age <96 months and allogeneic HSCT were significantly associated with the occurrence of HC: P=0.008 and 0.013, respectively. After a median follow-up of 5.75 years, the 5-year survival of patients who did or did not develop HC was: 43 vs 52%, P=0.03, respectively. This study indicates that age and type of HSCT are factors predisposing to HC in children given HSCT and demonstrates the promising role of HOT in a conservative approach to HC treatment.

Adolescent↗
PubMed2003

Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST).

We reviewed medical records of 256 patients to investigate the frequency and characteristics of hemorrhagic cystitis (HC) associated with reduced-intensity stem cell transplantation (RIST) as opposed to conventional stem cell transplantation (CST); 137 patients underwent CST and 119 RIST. Diagnosis of HC was made based on two or more episodes of sterile, macroscopic hematuria with normal coagulation profiles, without any evidence of renal stones or genitourinary malignancy. Actuarial frequency of HC development in RIST group was 7.6% (9/119), which gave a cumulative annual incidence of 11.7%. In CST group, 13 of 137 patients (9.5%) developed HC, giving an estimated annual incidence of 9.7%. The probability of developing HC was similar between the two groups (P=0.77). The viral etiologies of HC, adenovirus (n=12) and BK virus (n=2), were documented in eight patients after RIST and in six after CST. HC was milder and of a shorter duration, with less blood transfusion requirements, in RIST group than in CST group. A multivariate analysis revealed that HC was associated with antiadenovirus antibody positivity in the recipients, total dose of busulfan, and chronic GVHD. Although HC following RIST is less severe than that following CST, it is still a significant problem.

Adenoviridae↗
PubMed2003

Male predominance among Japanese adult patients with late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation.

Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell transplantation (HSCT) is mainly caused by viral infections. We retrospectively analyzed the records of 141 Japanese adult patients who underwent a first allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of 51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC patients, of whom eight had AdV type 11. Five of the six available serum samples from these patients were also positive for AdV type 11, but the detection of AdV in serum was not associated with a worse outcome. Male sex and the development of grade II-IV acute graft-versus-host disease were identified as independent significant risk factors for LHC. Male predominance was detected in LHC after HSCT, as has been previously shown in children with AdV-induced acute HC. The detection of AdV DNA in serum did not predict a poor outcome.

Adenoviridae Infections↗
PubMed2004

Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

Adenoviridae↗
PubMed2005

Polyoma BK virus and haemorrhagic cystitis in haematopoietic stem cell transplantation: a changing paradigm.

Haemorrhagic cystitis (HC) is a distinct clinical disorder of multiple aetiologies. It is characterized by painful haematuria due to haemorrhagic inflammation of the urinary bladder mucosa. In allogeneic haematopoietic stem cell transplantation (HSCT), HC occurring before engraftment is mostly transient and self-limiting, whereas that after engraftment is severe and sometimes life-threatening. Pre- and post-engraftment HC represent distinct disorders with different aetiologies and treatment implications. Recent data suggest that reactivation of the polyoma BK virus (BKV) plays a pivotal role in post-engraftment HC. Urotoxicity of the conditioning regimen and alloimmune reaction accompanying graft-versus-host disease (GVHD) upon engraftment are also important pathogenetic factors. Based on data from BKV studies, we propose that HC may be divided into three phases. In the first phase, the conditioning regimen damages uroepithelial cells, providing a milieu for BKV replication. In the second phase, unchecked uroepithelial BKV replication leads to BK viruria. In the last phase after engraftment, alloimmunity against BKV-infected uroepithelial cells leads to HC. The quinolone antibiotics suppress BKV replication in vivo and in vitro, suggesting that their prophylactic use may prevent the occurrence of HC.

BK Virus↗
PubMed2006

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Adolescent↗
PubMed2003

Systemic aspects of interstitial cystitis, immunology and linkage with autoimmune disorders.

It is recognized that interstitial cystitis (IC) is often associated with a number of diseases such as allergies, irritable bowel syndrome, fibromyalgia, inflammatory bowel disease (Crohn's disease and ulcerative colitis), systemic lupus erythematosus, and Sjögren's syndrome. The prevalence of allergies in IC is reported to be between 40 and 80% of patients. The background of the association is not known and does not seem to be the result of a generalized allergic constitution. Some report that treatment of allergy sometimes has a beneficial effect on bladder symptoms. An increased expression of certain growth factors (PD-ECGF, FGF, and VEGF) has been found in the bladder of IC patients. In addition, the expression of CD44 was significantly higher in ulcer type IC than in non-ulcer type. In general, these growth factors are soluble and diffusible under normal conditions but proteoglycans such as CD44 could bind to these growth factors. This may promote the accumulation of growth factors at the sites of inflammation. CD44 expression in ulcer type IC could explain the prolonged and stronger expression of GAG-binding growth factors that promote inflammation. In the Rotterdam study, a strong association between IC and Sjögren's syndrome is recognized. In this study, 28% of IC patients have definite or probable Sjögren's syndrome. This association is much stronger than is generally recognized. This could be due to difficulties in diagnosing Sjögren's syndrome since a diagnosis usually requires a high index of suspicion.

Autoimmune Diseases↗
PubMed2003

Significance of complications of allergic diseases in young patients with interstitial cystitis.

BACKGROUND: It was found that about one-half of interstitial cystitis (IC) patients have complications of allergic diseases. However, significance of the complications have not been studied. PATIENTS AND METHODS: Thirty-four patients (age range 20 to 39 years old) meeting the diagnostic criteria of NIDDK established in 1987 were selected. Clinical allergic tests and significance of complications of allergic diseases were examined. RESULTS: Eighty-six percent of young patients had complications of allergic diseases. In two patients, IC was a part of generalized allergic diseases. In 25 patients, IC was suggested to have some association with allergy. Of these 25 patients, there were alternating symptoms or proportionally changing symptoms of allergy and IC in 15 patients, and the number of eosinophils increased in six patients. Seven IC patients were considered to have developed allergic diseases only by chance without apparent association. CONCLUSIONS: Complications of allergic diseases are frequent, particularly in young IC patients. The results suggest the involvement of allergy in about 80% of IC patients with complications of allergic diseases. In only 6% of patients, IC was a part of generalized allergic disease.

Adult↗
PubMed2003

Research criteria versus clinical criteria for interstitial cystitis.

In March 2003 experts on interstitial cystitis (IC) from around the world met in Kyoto, Japan for a series of workshops intended to define areas of agreement and difference in the approach to this disease. This workshop explored the diagnostic criteria IC in the clinical and research settings. The NIDDK criteria are used almost universally for research but there is tremendous disparity in the clinics and no consensus at all as to the best practice in diagnosing IC for clinical purposes. Throughout the world many physicians use the NIDDK research criteria for clinical diagnosis; in some countries this is standard. Undoubtedly, this mandates under-diagnosis and denies treatment to many patients. Still, a majority feel that one diagnostic system is mandatory to promote clarity in communication. The group called for two initiatives to help advance this area of controversy: (1) a large-scale, prospective study critically examining the role of cystoscopy, bladder distention, and biopsy in the diagnosis of IC; (2) a concerted effort to develop a single evidence-based guideline or algorithm that would be flexible enough to meet the needs of clinicians, researchers, and patients.

Biomedical Research↗