Late onset hemorrhagic cystitis in a hematopoietic stem cell recipient: Treatment with intravesical hyaluronic acid

Abstract

HC is a common complication following HSCT. Risk factors include viral infections, cyclophosphamide and busulfan usage, pelvic irradiation, older age at transplantation, allogeneic HSCT and GvHD. The severity of HC ranges from mild hematuria to life-threatening bleeding. Here, we present a seven-and-a-half-yr-old boy with Wiskott-Aldrich syndrome who experienced a late onset Grade III hemorrhagic cystitis following HSCT from his fully matched sibling. A Grade I GvHD localized to skin developed on day +11 and prednisolone therapy was given between the 11th and 22nd d. Myeloid and platelet engraftments were achieved +13 and +16 d, respectively. A gross hematuria began on the 21st post-transplant day. The urine cultures for bacterial or fungal organisms were negative. Urine analysis by PCR revealed a CMV viruria. Following systemic ganciclovir treatment, urinary CMV became negative but hemorrhagic cystitis did not improve. Due to the probability of existing BK virus or adenovirus, two doses of cidofovir were administered intravesically. As he continued to have painful hematuria with large clot formations, two doses of intravesical hyaluronic acid were applied. Macroscopic hematuria resolved within four d after the second dose. Complete remission was achieved on day +77. Finally, intravesical administration of hyaluronic acid seems to be effective and safe and can be a promising treatment in patients suffering from severe and late onset HC.

Emergent Complications in the Pediatric Hematopoietic Stem Cell Transplant Patient

“…Early-onset HC is most often due to direct uroepithelial insult from cyclophosphamide, or other alkylating agents, in the conditioning regimen. 60,62-64,66-69 It has been shown that the accumulation of cyclophosphamide metabolites in the bladder directly damages the bladder wall. 69 With hyperhydration and the introduction of Mesna prophylaxis in the late 1970s, the incidence of cyclophosphamide-induced HC has drastically decreased.…”

“…In cases of mild HC, hydration, forced diuresis, platelet transfusions to keep a platelet count of greater than 50 000/ mm 3 , pain management, and antispasmodics such as oxybutynin may be sufficient. 60,62,64-66 Renal ultrasound should be used to look for clots in the bladder and/or kidneys. When patients are passing clots, they typically require Foley catheter insertion with continuous bladder irrigation until the bleeding can be controlled.…”

“…The effort to relieve the obstruction needs to be initiated quickly; therefore, prompt urologic evaluation is often advisable. In patients who have refractory bleeding, several other treatments have been tried with variable success, including intravesicular hyaluronic acid, 66 intravesicular alum, 71 intravesicular formalin, 63 intravesicular prostaglandins, 72,73 and hyperbaric oxygen. 65,74-76 For BK and adenovirus viruria, the antiviral agent cidofovir has shown promising results.…”

Pharmacological Options for Viral Induced Hemorrhagic Cystitis Management: A Review of the Literature

“…Hyaluronic acid, also known as sodium hyaluronate in salt form, is a glycosaminoglycan found on bladder mucosa which prevents uro-epithelial damage by forming a protective barrier [72,73]. Additionally, it has been hypothesized that hyaluronic acid may affect viral replication of BKV [72].…”

Management of refractory hemorrhagic cystitis following hematopoietic stem cell transplantation in children

“…A seven‐yr‐old boy with HC following HSCT did not respond to the treatment with systemic gancyclovir and intravesical cidofovir. However, hematuria resolved after two administrations of hyaluronic acid (88).…”