Cyclophosphamide-induced hemorrhagic cystitis: A review of 100 patients

Stillwell, Thomas J.; Benson, Ralph C.

doi:10.1002/1097-0142(19880201)61:3<451::aid-cncr2820610308>3.0.co;2-g

Cited by 274 publications

(153 citation statements)

References 32 publications

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“…Severe HC is a rare but potentially devastating complication of BMT, which causes pain, prolonged hospitalization, and significantly increases cost of transplants. 2,14,[26][27][28] Although HC can be secondary to a variety of factors (drugs, radiation, infections), HC in the BMT setting is usually either related to the use of CY or, later in the course of the transplant, to viral infections. [2][3][4][5][6][7][8]14 CY has been widely used for conditioning patients for BMT.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

151

137

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Summary:Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graftversus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P Ͻ 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna. Keywords: bone marrow transplantation; complications; hemorrhagic cystitis; risk factors; adenovirus; cytomegalovirus Outcome after bone marrow transplantation (BMT) has improved over the past 20 years, 1 but preparative regimenrelated toxicities (RRT) remain a major limitation to further progress. Hemorrhagic cystitis (HC) is a common RRT. 2 In the BMT setting, HC occurring in the early post-transplant period is more frequently associated with the use of cyclophosphamide (CY), while late occurring HC frequently results from viral infections (eg BK virus, adenovirus type II). 3-8 CY has been widely used for conditioning patients undergoing BMT. The drug is hydroxylated in the liver, generating 4 hydroxy-CY, phosphoramide mustard, and acrolein. Excreted in the urine, acrolein can cause edema,

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Section: Discussionmentioning

confidence: 99%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

151

137

View full text Add to dashboard Cite

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“…2 The term 'late-onset HC' is used to exclude CY-induced HC in patients undergoing HSCT. It is well known that CY often induces early-onset HC, 19 which usually occurs during or immediately after CY administered as part of the conditioning regimen. In the majority of patients, HC has been attributed to a direct toxic effect of CY metabolites on the urothelium.…”

Section: Discussionmentioning

confidence: 99%

Late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation in children

Kondo

Kojima²,

Kato³

et al. 1998

Bone Marrow Transplant

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Summary:We analyzed the incidence, complications, and risk factors for late-onset hemorrhagic cystitis (HC) in 256 children undergoing hematopoietic stem cell transplantation (HSCT). Twenty-six recipients (10.2%) developed late-onset HC between 3 and 270 days (median, 33 days) after HSCT. In most patients, the severity of HC was mild to moderate, and spontaneous resolution occurred. Three children developed bladder tamponade, and one required suprapubic cystotomy. Four children died in the early post-transplant period without resolution of HC, but HC was not the direct cause of death in any patient. Twenty-two patients recovered within 6-86 days (median, 16 days) of onset. Three predisposing factors were identified for development of late-onset HC by multivariate analysis: allogeneic HSCT, older age (у7 years), and busulphan for pretransplant conditioning were significantly associated with late-onset HC (P ‫؍‬ 0.022, P ‫؍‬ 0.044 and P ‫؍‬ 0.036, respectively). Excretion of adenovirus type 11 was demonstrated in six of 22 patients at the onset of cystitis. We suspect that reactivation of virus may be a major pathogenic factor in lateonset HC, but several clinical factors are also associated.

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“…Hemorrhagic cystitis is a known adverse effect of this drug and may be the limiting factor in its use (2,3). In the absence of adequate uroprotection, the incidence of this side effect of CYP therapy varies from 2 to 40% in patients taking low doses of CYP on a long-term basis (4).…”

mentioning

confidence: 99%

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

Morais

Belarmino-Filho

Brito

et al. 1999

Braz J Med Biol Res

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Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P<0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P<0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYPinduced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection.

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Cyclophosphamide-induced hemorrhagic cystitis: A review of 100 patients

Cited by 274 publications

References 32 publications

Risk factors for severe hemorrhagic cystitis following BMT

Risk factors for severe hemorrhagic cystitis following BMT

Late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation in children

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

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