Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients.

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.

Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

A nine-yr-old girl developed AdV-associated HC after bone marrow transplantation. Intravenous GCV markedly reduced urinary AdV DNA loads and improved clinical findings. This appeared to result partly from a high concentration of GCV in urine. GCV may be effective for AdV-induced HC without definitive disseminated infection.

BKV infection and hemorrhagic cystitis after allogeneic bone marrow transplant.

Hemorrhagic cystitis (HC) is a well-known complication after allogeneic bone marrow transplant (BMT) and can be related to adenovirus or human polyomavirus BK (BKV) infections. In this study a group of 20 patients after allogeneic BMT has been examined. BMT urine samples were analysed for the presence of Adenovirus and BKV DNAby means of polymerase chain reaction (PCR). 5/20 BMT patients developed HC after BMT. The presence of BKV DNA in urine samples was evident in 3/15 patients without HC and in 5/5 patients with HC. In 2/5 HC-patients the BKV DNA was not found after therapy with Cidofovir and Ribavirin. The search for adenovirus DNA in all samples was negative. The analysis of BKV non-coding control region (NCCR) isolated from urine samples revealed a structure very similar to the archetype in all samples. The RFLP (Restriction Fragment Length Polymorphism assay) showed the presence of BKV subtypes I and IV, with the prevalence of subtype I (4/5). This study supports the hypothesis that HC is mainly related to BKV rather than to adenovirus infection in BMT patients. Moreover, since BKV subtype I was predominant, it is reasonable to hypothesize that a specific BKV subtype could be associated with the development of HC.

Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation.

We describe a method of diagnosing virus-associated cystitis after allogeneic bone marrow transplantation (BMT) and treatment with vidarabine therapy. At 7-10 days post-BMT when cystitis was suspected, we observed urinary sediments by the Papanicolaou stain to detect virus inclusion bodies. When positive, we examined urinary sediments by transmission electron microscope and measured the diameter of viral particles to determine the families. This process needed only 4 days. Among 16 consecutive cases, adenovirus and polyomavirus were each detected in three. Adenovirus caused hemorrhagic cystitis in two cases and cystitis without macroscopic hematuria in one case. Polyomavirus caused cystitis without macroscopic hematuria in one case. Polyomavirus was also detected in two cases without any symptoms. Vidarabine (10 mg/kg/day i.v.) was administered for 5 days as one course. Soon after one course of vidarabine, most symptoms subsided and virus inclusion bodies disappeared in all cases except for one with severe hemorrhagic cystitis. From these experiences, vidarabine reduces excretion of adenovirus and polyomavirus in the urine of BMT recipients and improves clinical symptoms in some cases of cystitis associated with these viruses.

A prospective study of corticosteroid and catecholamine levels in relation to viral respiratory illness.

Urinary 17-OHCS, epinephrine and norepinephrine levels were studied for one week before and one week after the onset of acute, severe Adenovirus 4 respiratory illness in 12 Army recruits during Basic Combat Training. During the pre-illness period, a tendency was frequently noted for all three hormone levels to show "spiking" elevations two to four days before illness onset. There was also a tendency for 17-OHCS levels to rise on the day before fever onset. The possible relationship of these pre-illness hormonal changes to stressful experiences and, in turn, to altered host resistance to infectious illness is discussed. Following onset of respiratory illness, 17-OHCS, epinephrine and norepinephrine levels all showed about 60 percent increases over the early pre-illness period baseline value. Elevations of these hormones persisted for about four to five days, roughly in correlation with fever duration, with only slight differences in configuration and timing of curves from one hormone to the next. The problem of evaluating which of several independent variables operating concurrently during infectious illness may be responsible for stimulating the final common neuroendocrine pathways is discussed.

Experimental infection of calves with an adenovirus isolated from sheep and related to bovine Adenovirus type 2 I. Clinical and virological studies.

Colostrum deprived calves were experimentally infected with an adenovirus isolated from sheep and related to bovine adenovirus type 2. The calves showed respiratory symptoms and mild diarrhoea from the third day after infection. Laboratory tests revealed the development of leucopenia, lymphopenia, a drop of the pH of the urine and the appearance of pathological changes in the urine. The animals shed the virus in their nasal discharge, faeces and urine. Comparing the clinical and virological findings with the previous experimental infection of lambs it is concluded, that this type of adenovirus is similarly pathogenic for the two ruminant species.