Hyperbaric Oxygen Therapy for Control of Intractable Cyclophosphamide-Induced Hemorrhagic Cystitis

Summary:The purpose of this multicenter study was to assess the incidence and the treatment of hemorrhagic cystitis (HC) in 1218 pediatric patients, with a mean age of 10.8 years, who underwent hematopoietic stem cell transplantation (HSCT). In all, 44 patients (3.6%) developed HC a median 23 days after HSCT. The incidence of HC was higher in allogeneic than in autologous HSCT recipients (P ¼ 0.0001). Of the 44 patients, 37 (84%) recovered from HC in a median 30 days (range 3-100); the other seven children died while still suffering from HC. Hyperbaric oxygen therapy (HOT) achieved significantly better results than prostaglandin therapy (P ¼ 0.02) in the treatment of grade II-III HC. By multivariate analysis, age o96 months and allogeneic HSCT were significantly associated with the occurrence of HC: P ¼ 0.008 and 0.013, respectively. After a median follow-up of 5.75 years, the 5-year survival of patients who did or did not develop HC was: 43 vs 52%, P ¼ 0.03, respectively. This study indicates that age and type of HSCT are factors predisposing to HC in children given HSCT and demonstrates the promising role of HOT in a conservative approach to HC treatment. Bone Marrow Transplantation (2003) 32, 925-931.

Section: Discussionmentioning

confidence: 99%

Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology–bone marrow transplantation group

Cesaro

Brugiolo

Faraci

et al. 2003

“…Two case reports have recently been published in which cyclophosphamide-induced cystitis was treated successfully with hyperbaric oxygen. 13,14 Both cases had failed several conservative treatments before hyperbaric oxygen was used.…”

Section: Discussionmentioning

confidence: 99%

Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis

Hughes

Schwarer

Millar

1998

Summary:Haemorrhagic cystitis is a common and often debilitating complication of chemotherapy for which treatment is frequently unsatisfactory. With over 80 cases reported of radiation-induced cystitis treated successfully with hyperbaric oxygen, attention is now turning to the treatment of chemotherapeutic agent-induced cystitis. We report a case of haemorrhagic cystitis occurring after autologous peripheral blood stem cell transplantation for multiple myeloma. The patient had received cyclophosphamide and busulfan and had BK and adenoviruria. The haemorrhage was refractory to multiple conventional treatments but resolved after a course of hyperbaric oxygen. Keywords: haemorrhagic cystitis; hyperbaric oxygen; cyclophosphamide; adenovirus; BK virus Hyperbaric oxygen was administered in a multiplace chamber. The treatment plan was based on that which would be used to treat radiation-induced cystitis.1,2 The patient received 100% oxygen for 80 min at an absolute pressure of 2.4 atmospheres. The total duration of each treatment was 99 min. One treatment per day was administered, 5 to 6 days per week. The end-point for treatment was resolution of haematuria. Case historyA 41-year-old man was diagnosed with multiple myeloma in August 1995 after presenting with sudden onset of backpain. Bone marrow examination showed 32% plasma cells and an IgG paraprotein of 30 g/l was present in the serum. On the 5th post-transplant day, the patient became febrile and developed dysuria. The urine was noted to be rosé in colour. He was started on anti-bacterial antibiotics and urine was sent for BK virus, adenovirus and CMV isolation. By the 8th post-transplant day, he had progressed to severe bladder spasms and gross haematuria. A clinical diagnosis of haemorrhagic cystitis was made.An indwelling catheter was inserted. Continuous bladder irrigation was commenced. Adenovirus was cultured from the urine on the 13th post-transplant day and PCR for BK virus was weakly positive. Engraftment occurred on the 14th post-transplant day. On the 15th day, alum (1% solution) washouts were commenced and were continued for 1 week. By the 22nd day, haemorrhage was still uncontrolled requiring the introduction of intravesical prostaglandin F2 alpha (PGF2 alpha) 200 g in 50 ml normal saline instilled for 1 h or as long as tolerated. This was repeated at 4 hourly intervals. PGF2 alpha was poorly tolerated by the patient due to extreme pain and was subsequently performed in the operating room under general anaesthesia. PGF2 alpha was continued for a further 5 days with no benefit. On the 24th day the patient underwent flexible cystoscopy which confirmed widespread mucosal ulceration consistent with haemorrhagic cystitis. From the 27th to the 37th day, the patient was treated with intravenous ribavirin (9 mg/kg intravenously 8 hourly) during which time his fever settled but haematuria continued. The patient underwent rigid cystoscopy, diathermy and instillation of silver nitrate on the 33rd day. Alum irrigation was recommenced following cessation of rib...

“…14 Numerous therapeutic approaches have been tried to control pain and bleeding but often without success. [15][16][17][18][19][20][21][22][23][24][25] Because of the severity of HC and difficulty in its treatment, maximal efforts have been made to prevent this complication. Sodium 6 mercaptoethane sulfonate (Mesna) is a sulfhydryl compound that binds to acrolein, and therefore prevents urothelial damage.…”

mentioning

confidence: 99%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

156

137

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,