Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation

Abstract

Summary:Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen. Bone Marrow Transplantation (2001) 27, 1315-1317. Keywords: hemorrhagic cystitis; hyperbaric oxygen; allogeneic bone marrow transplantation; children Hemorrhagic cystitis (HC) is a major complication following hematopoietic stem cell transplantation. Severe cystitis has been reported to occur in about 5% of bone marrow transplant (BMT) patients. Allogeneic BMT, grade II-IV graft-versus-host disease (GVHD), use of busulfan (Bu), age at transplantation and adenovirus infection increase the risk of severe HC. 1 Many therapeutic approaches have been tried to control pain and bleeding due to HC; despite this, HC can lead to bladder tamponade requiring surgical intervention, and can contribute to death. Hyperbaric oxygen (HBO) therapy has been used extensively in hypoxic tissue in an attempt to stimulate angiogenesis and prompt healing. HBO has been used successfully in the treatment of radiation or cyclophosphamide (CY)-induced HC. 2,3 This is the first report in patients with intractable HC after allogeneic BMT who were controlled by HBO. Case histories Case 1An eight-year-old boy with acute lymphocytic leukemia in third remission underwent BMT from an HLA-matched unrelated donor in June 1998. He received a conditioning regimen of Bu 4 mg/kg/day for 4 days, CY 60 mg/kg/day for 2 days, and etoposide 60 mg/kg/day for 1 day. Cyclosporine A (CsA) and prednisolone were administered for GVHD prophylaxis. The clinical course after BMT is shown in Figure 1. By the fifth week after BMT, trilineage engraftment was confirmed. The patient did not develop acute GVHD. At day +4 he had developed dysuria, suprapubic pain and macrohematuria. On day +70 he developed gross hematuria with clots and an abundant residue of bladder mucus. Adenovirus was not cultured from the urine, and HC was not attributed to polyomavirus infection because characteristic morphologic changes in the urinary sediment were not seen in conjunction with the urine culture being negative for other pathogens. During the next 9 weeks, gross hematuria continued, and the patient required seven transfusions of packed red blood cells and 33 transfusion of platelets. Despite conservative treatment with continuous bladder irrigation and intravesicular maalox and prostaglandin E1 (PGE1), he developed bladder tamponade on days +78 and +118 after BMT requiring emergency cystostomy and evacuation of hematomas. Post-renal failure developed, and he was referred for HBO therapy after bilateral tympanostomies. The patient was ...

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

“…The efficacy of HOT in HC induced by pelvic irradiation has already been reported by several authors, [22][23][24][25] but only anecdotal reports have analyzed the role of HOT in HC after HSCT. 25,58 The high cure rate (78.5%) obtained in our study, in patients refractory to other medical treatments, suggests that HOT may play an important part in a conservative approach to HC in HSCT recipients too. Other potential advantages, such as a faster recovery from HC, the need for fewer transfusions and a shorter hospital stay should be addressed by future controlled trials.…”

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

“…Hyperbaric oxygen therapy for HC patients has achieved encouraging success with no adverse effects in recent years, 25 especially for the patients induced from radiation, 40 which allows better tissue diffusion of oxygen, improving neoangiogenesis by increasing the vascular density of irradiated tissues. However, the wide application of this approach is limited by the requirement of a hyperbaric chamber and long procedure (20-30 days).…”

“…[14][15][16][17] The use of formalin, alum, prostaglandin E1, estrogens, FVIIa, factor XIII, hyperbaric oxygen treatment, intravesicular sodium hyaluronate, recombinant human epidermal growth factor or recombinant human GM-CSF has been described, but their efficacy remains controversial. [18][19][20][21][22][23][24][25][26][27] Severe HC may also require surgical treatment with cystoscopy and cauterization, and even cystectomy when previous methods have failed, 28 but it is limited by the disadvantage of operation.…”

Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate

“…23,24 Hyperbaric oxygen therapy has been shown to be effective for HC due to chemotherapy and/ or radiation therapy, and two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen have been reported. 25 Surgical interventions such as cystectomy, nephrostomy, ureterostomy are associated with high rates of morbidity and mortality and are indicated for life- 27,28 Sodium hyaluronate (a member of glycosaminoglycans), is a major component of the extracellular matrix of most tissues. High concentration of glucosaminoglycans are present in the uroepithelium, and constitute a protective barrier against irritating agents that can potentially cause damage to epithelium.…”