Risk factors for and prognosis of hemorrhagic cystitis after allogeneic stem cell transplantation: Retrospective analysis in a single institution

Abstract

Hemorrhagic cystitis (HC) is a major complication after allogeneic stem cell transplantation (allo-SCT) and can be life threatening. To analyze risk factors and prognosis, we retrospectively reviewed 249 cases receiving allo-SCT in our institution. Median age was 47 years (13-72 years). Disease status at SCT was progressive in 73 cases. Conditioning was myeloablative (MAC) in 146 cases. Acute graft-versus-host disease (aGVHD) grade II-IV treated with prednisolone occurred in 82 cases, and cytomegalovirus (CMV) was reactivated in 91 cases. HC was reported in 47 cases at a median of 35 days (7-469 days) after SCT, and 34 (72.3%) cases recovered after a median of 19.5 days (2-252 days). In univariate analysis, the identified risk factors for HC included age over 45 years, progressive disease status, MAC, aGVHD treated with prednisolone, and CMV reactivation. In multivariate analysis, older age, MAC, and CMV remained independent predictors (hazard ratios: 2.35, 3.50, and 2.87). In patients with severe HC, percentage recovery was lower (3 in 13 cases; 23.1%) and the median duration was longer (54 days) than in those with moderate HC (31 in 36 cases; 86.1%, 17 days, P < 0.01). Treatment-related mortality was also higher (59.1%, P = 0.03) and overall survival was poorer (16.7%, P < 0.01) at 1 year after SCT. Prospective studies should be started considering prophylactic antiviral administration in high-risk patients such as those identified in this study.

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival

“…Some studies found no relation between dose of cyclophosphamide 19, 31, 44, 45 or interaction with TBI. Conditioning regimen intensity has also been studied and MAC has been reported to induce with higher frequency of HC 1, 8, 10, 22, 39, 46, 47 . It was argued that MAC induced more HC in part due to increased risks for BK viruria 47 .…”

“…Our study identified GVHD as a significant clinical variable associated with HC and fewer patients had active GVHD at the resolution of HC compared to onset. Other studies have identified GVHD as a risk factor for the development of HC; especially severe or late-onset HC 10, 19, 22, 32, 40, 41, 54, 55 . However, it remains unknown whether GVHD targeting bladder epithelium manifests as HC or whether immunosuppression from acute GVHD and/or concomitant steroid use contributes to HC and its severity 19, 56, 57 .…”

“…We identified no significant association between adenovirus, HHV-6 or CMV in HC patients comparing the onset and resolution of HC. Some studies have associated CMV reactivation with HC 10, 22 , suggesting that DNA viruses such as CMV can induce BK virus replication. 58, 59 .…”

“…Several predisposing factors have been reported including transplant type, age at transplantation, presence of graft-versus-host disease (GVHD), donor source, and conditioning regimen components and intensity 1, 12, 19–21 . The effect of HC on survival remains controversial, but its morbidity can be substantial, even in survivors 10, 22 .…”

Increased non‐relapse mortality due to high‐dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults

“…Strong HDCA cytotoxicity combined with significantly poor neutrophil engraftment might cause virus reactivation and virus‐induced haemorrhagic cystitis. The higher incidence of IP and haemorrhagic cystitis were not observed in CBT (Arai et al , ); the relatively higher baseline incidence of GVHD after BMT/PBSCT (compared to CBT) could explain this difference, because both IP and haemorrhagic cystitis are closely related to the preceding GVHD (Krowka et al , ; Arai et al , ).…”