Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation

Abstract

Summary:Haemorrhagic cystitis (HC) is an important complication after bone marrow transplantation (BMT). Overt HC (grade у2, gross haematuria, clot retention and impairment of renal function), clinically more important than mild and occult HC (grade 1, microscopic haematuria), leads to substantial morbidity and occasional mortality. We retrospectively analyzed 32 cases of clinically overt HC from a series of 236 BMT patients. Significant risk factors included the use of busulphan during conditioning, allogeneic BMT and acute GVHD. Logistic regression showed GVHD to be the most important risk factor. According to the time of engraftment, HC could be divided into pre-and postengraftment subtypes. Pre-engraftment HC was brief, not more severe than grade 2, and subsided with supportive treatment. In contrast, post-engraftment HC was protracted, often of grade у3, associated with severe GVHD, and required surgical intervention in many cases. Polyoma BK viruria, but not adenoviruria, could be demonstrated in both types of HC. The increased severity and association with GVHD of postengraftment HC suggested that attack of urothelium by immunocompetent cells, possibly directed against BK viral antigens, might play a pathogenetic role.

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

“…1 Post-engraftment HC is strongly associated with BKV, although the role of BKV in its pathogenesis has not yet been fully elucidated. 1,3,7,8,10,11,23,24,[29][30][31][32] In this study, BKV viruria was detected in 83.7% among patients who had urine PCR BKV testing in the presence of a diagnosis of HC. This is comparable to previously published rates of post-engraftment BKV viruria ranging from 79 to 100%.…”

“…21,22 Several risk factors for HC associated with BKV after allo-HSCT have been suggested, such as conditioning regimens containing BU, acute GVHD (aGVHD), intensity of conditioning regimen, donor type, CMV seropositivity and post-transplant mycophenolate use. 4,8,10,23,24 However, these are yet to be confirmed.…”

“…This is comparable to previously published rates of post-engraftment BKV viruria ranging from 79 to 100%. 3,7,10,23 However, more than half of the patients remained asymptomatic with BKV viruria. 29,[33][34][35] With the advent of quantitative BKV PCR techniques, BKV load in the urine was quantitatively related to the occurrence of HC.…”

“…[1][2][3][4][5][6] While early-onset HC is usually mild with microscopic hematuria and secondary to the chemoradiation (e.g., CY), more severe HC with gross hematuria develops in the later course of allo-HSCT (⩾30 days after transplant) and is strongly associated with BK virus. 1,3,[7][8][9][10][11][12] Polyomavirus BK (BKV) is a double-stranded non-enveloped DNA virus first isolated from a urine sample obtained from a renal transplant recipient. [13][14][15] Primary infection occurs in childhood and remains in a latent phase most commonly in the kidney.…”

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

“…Moreover, the ubiquitous use of BU may also explain the lack of difference as other studies have proven BU to be a risk factor of HC development. [24][25][26] As the urinary tract is the main site of BKV latency, it is expected to be the first site of reactivation. Transient BK viruria occurs in all allo-HSCT patients 19 with 4-25% of the patients developing sustained BKV-HC.…”