Incidence, Clinical Outcome, and Management of Virus-Induced Hemorrhagic Cystitis in Children and Adolescents after Allogeneic Hematopoietic Cell Transplantation

Abstract

We analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (HC) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. Conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). In all children, urine and plasma were prospectively screened for human polyomavirus (HPV; BK virus [BKV] and JC virus [JCV]) or adenovirus (AdV) DNA with a polymerase chain reaction-based assay. Viral DNA was detected in the urine of 56 children (54.9%): BKV in 48 (47%), JCV in 4 (3.9%), and AdV in 4 (3.9%). HC occurred in 26 children (25.5%), and viruria was detected in all of them: BKV in 21 (80.8%), AdV in 4 (14.4%), and JCV in 1 (3.8%). All patients with AdV viruria developed HC. The cumulative incidence of HC in patients with HPV viruria was 0.43. The only significant risk factor for HC in patients with HPV-positive urine was conditioning with high-dose chemotherapy. Twenty-two children were treated with cidofovir, with no significant toxicity. In all treated patients but 1, the clinical symptoms were moderate, and no HC-related death was observed. We conclude that virus-induced HC is a frequent complication after allogeneic hematopoietic cell transplantation. Treatment with cidofovir is feasible, and further studies are warranted to evaluate its activity in HC mediated by BKV or JCV.

A prospective study of BK-virus-associated haemorrhagic cystitis in paediatric patients undergoing allogeneic haematopoietic stem cell transplantation

“…33,34 In the paediatric HSCT setting, other authors have suggested a link between HuPyV infection and HC: for example, Gorczynska et al found that 22 of 52 (42%) HSCT patients with HuPyV viruria (BK, 48, JC, 4) developed HC; while Leung et al found that 2 of 11 (18%) patients with quantifiable BK viruria had HC. 21,34,35 This prospective study gives further relevance to the role of BK virus infection for HC in paediatric HSCT. We found that 87.5 and 75% of post-HSCT HC patients were associated with BK positivity in urine and/or blood, respectively, and that BK infection was the only risk factor for the development of HC.…”

“…25 The initial treatment of HC consisted of supportive measures (hyperhydration, forced diuresis and/or bladder irrigation). For patients with persistent bleeding, therapy with prostaglandins, GM-CSF and 1,26 cidofovir (CDV) 21,27 and hyperbaric oxygen therapy were used at the discretion of the transplant physician. 1 In patients with BK-related HC and no signs of active acute GVHD, a reduction or temporary withdrawal of immune suppression was tried.…”

“…3,13,[15][16][17][18] Importantly, the paediatric data published so far have mainly addressed the epidemiological aspects and analysed the risk factors, 1,19,20 while data on the association between BK viral infection and HC post-HSCT are more limited. 11,17,21 We report the results of a prospective study on the incidence of late-onset HC, together with risk factors, and also report the sensitivity, specificity, and positive and negative predictive values of BK viruria and viraemia for developing HC, in paediatric onco-haematological patients undergoing allogeneic HSCT.…”

Selective embolization of the internal iliac arteries for the treatment of severe hemorrhagic cystitis following hematopoietic SCT

“…Hemorrhagic cystitis (HC) is recognized as a significant cause of morbidity and sometimes mortality in patients undergoing hematopoietic SCT (HSCT) [1][2][3] shows a clinical manifestation varying from microscopic hematuria to severe hemorrhage with obstructive renal failure. 4,5 Its reported incidence ranges from less than 10% to more than 70% due to the discrepancies in definition criteria and the types of transplant.…”

“…Routine therapy for HC is based on intensive supportive treatment with hyperhydration, constant bladder irrigation, pain management and red cell or platelet transfusions. 2,13 Encouraging results with antiviral agents have been published; however, there is no evident proof in a large number of patients and mainly improve clinical symptoms. [14][15][16][17] The use of formalin, alum, prostaglandin E1, estrogens, FVIIa, factor XIII, hyperbaric oxygen treatment, intravesicular sodium hyaluronate, recombinant human epidermal growth factor or recombinant human GM-CSF has been described, but their efficacy remains controversial.…”