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

Abstract

Summary: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 lifethreatening. 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 postengraftment 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. Bone Marrow Transplantation (2005) 36, 929-937.

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

“…Along with the quantitative correlation between BKV viruria and the development of HC, this may suggest that the host immune response has an important role in the reactivation of BKV in uroepithelium and the subsequent development of HC. 36 Many studies have tried to identify the risk factors for BK-HC in allo-HSCT. 1,3,4,10,23,24,28,31,32,37 Older age was identified as a risk factor in pediatric HSCTs, 2,3,31 but no other risk factor has been consistently verified in adult HSCTs, although aGVHD, BU-based conditioning regimens, the type of HSCT and the intensity of conditioning have been suggested.…”

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

“…The reactivation of polyomavirus such as BK virus has been thought to be the most significant factor in the pathogenesis of LOHC, some other studies provide information of adenovirus, CMV and simian virus 40 as putative agents of HC. [9][10][11][12] Other reported factors include GVHD, unrelated BM or cord blood transplants, radiation and exposure to BU. 1,[34][35][36] The Embolization treatment of hemorrhagic cystitis after HSCT Y Han et al immune reactions play an important role in the pathogeneses of LOHC, which may lead to the immune attack of the recipient urothelium, causing more damage than the simple toxic effects of chemotherapy or the cytopathic effects of viral infections.…”

“…Early-onset HC occurs within a few days after transplantation and results from urothelial injury induced by chemotherapeutic agents, most commonly CY and ifosfamide, 8 whereas late-onset HC (LOHC) occurs later after transplantation, and is more frequently associated with viral infections. [9][10][11][12] According to the amount of hematuria, HC is graded as mild, moderate or severe. Routine therapy for HC is based on intensive supportive treatment with hyperhydration, constant bladder irrigation, pain management and red cell or platelet transfusions.…”

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

“…1,18,29,30 Consistent with these data, all the patients in our study had a BK viruria higher than 10 8 copies/mL indicating that BK viruria may not be the most relevant factor for the prediction of BKV-HC severity. As proposed by Bedi et al and others,17,23,31,32 BKV-HC is a threestep process, in which the last phase corresponds to hematopoietic reconstitution. This leads to uroepithelial injuries and hemorrhages, which may promote systemic dissemination through BKV release from the uroepithelial focus.…”