Intravesical rhGM-CSF for the treatment of late onset hemorrhagic cystitis after bone marrow transplant

Abstract

Summary:In the present study, we assessed the clinical effect of recombinant human granulocyte-macrophage colonystimulating factor (rhGM-CSF) in the treatment of refractory, grade III-IV hemorrhagic cystitis (HC) in six patients who underwent bone marrow transplantation (BMT). These were four males and two females, aged 24-40 years (median age 30.5 years). All received allogeneic BMT from HLA-identical siblings after preparation with busulfan-cyclophosphamide. HC was evident 24.5 days (range 15-33 days) after BMT. Median duration of HC before treatment was 5 days (range 4-9 days). Treatment consisted of intravesical instillation of rhGM-CSF (400 g) for 3 consecutive days. A complete response was observed in three patients, the other three showed a partial response. Median time to achieve response was 36 h (range 0.2-72 h). Hematuria was controlled after the first (two patients), second (two patients) or third (two patients) dose of intravesical rhGM-CSF. Patients were discharged from the hospital 10.5 days (range 3-41 days) after treatment. All patients have been followed for up to 10 months and none have required further treatment. No systemic or bladder side-effects have been observed. Although our results indicate that intravesical instillation of rhGM-CSF is effective in the treatment of HC, a phase II clinical trial, including a larger series of patients, is needed. Keywords: GM-CSF; hemorrhagic cystitis; BMT Hemorrhagic cystitis (HC) is a well-recognized and potentially fatal complication commonly observed in patients who receive high-dose cyclophosphamide (Cy). The incidence in BMT patients is 10-20%. 1-3 Acrolein, a metabolite of Cy, has been implicated as a causative agent. 4 HC after high-dose Cy is prevented by bladder irrigation, hyperhydration 5 and sulfhydryl-containing compounds such as 2-mercapto-ethane (mesna), 6 that inactivate acrolein in the urine. Other known causes of HC include exposure to busulfan, radiation, GVHD and viruses including adenovirus, 7 polyomavirus 8 and cytomegalovirus.HC can be treated by performing hyperhydration, intraCorrespondence: Dr J Vela-Ojeda, Apartado postal 14-878, código postal 07001, México, DF México

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

“…18 Intravesicular sodium hyaluronate or recombinant human epidermal growth factor are other local treatment choices but need to be tested in larger cohorts of patients. 22,24 Recombinant human GM-CSF in intravesical instillation has been reported to be successful for the treatment of HC, 23 and we treated our patients with intravesical instillation of GM-CSF after HC onset, but no effective result was observed.…”

“…[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.…”

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation

“…6 --9 Patients with viral infection may be treated with anti-viral agents, but their efficacy is limited. 8,9 Hyperbaric oxygen (HBO) may benefit patients with BK virus (BKV) -associated HC after HSCT. 5,10 --16 HBO has been shown effective in the treatment of radiation-induced HC, 17 --19 by promoting fibroblast proliferation and capillary angiogenesis, decreasing edema and facilitating damaged hypoxic urothelium.…”

Successful treatment of severe hemorrhagic cystitis with selective vesical artery embolization

“…Other therapeutic strategies used have included local instillation of prostaglandin, phenol, alum, formalin, estrogens, epidermal growth factor and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). 4,5 If a viral infection is detected, the administration of antiviral agents is indicated. 6 Hyperbaric oxygen therapy has been associated with a few successes.…”