EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Acute lymphoblastic leukemia, BK virus, Hematuria, Polyomaviridae, Treatment

Hemorrhagic cystitis is characterized by hemorrhagic inflammation of the bladder mucosa and painful micturition with hematuria. It frequently is observed in immunocompromised patients after chemotherapy, radiation therapy, or hematopoietic stem cell transplant. The BK virus (a member of the Polyomaviridae family) was first isolated in a urine culture of an asymptomatic immunocompromised patient.¹ Primary infection with BK virus usually occurs during childhood and is followed by a latent period. Infection with BK virus during hematopoietic stem cell transplant or chemotherapy is caused by reactivation of latent virus, but new infection or reinfection may occur.² Optimal treatment for hemorrhagic cystitis caused by BK virus has not been established. The antiviral agent cidofovir has the highest known specificity against BK virus but is limited in routine use because of nephrotoxicity.³ Other treatments have included systemic estrogen therapy, systemic recombinant activated factor VII, or intravesical instillation of prostaglandins, growth factors, or fibrin glue.^4-7

A 13-year-old boy was treated for high-risk acute lymphoblastic leukemia with the Berlin-Frankfurt-Munich protocol. He developed painful macroscopic hematuria soon after the second block of reinduction therapy. Laboratory tests showed hemoglobin level 98 g/L, white blood cell count 0.1 × 10⁹/L, and platelet count 21 × 10⁹/L. Serum urea, creatinine, and electrolyte levels were normal. Urine microscopy showed erythrocytes with normal morphology. Repeated urine samples for culture were sterile. Serum complement and cystatin C levels were normal, which suggested that he did not have glomerular pathology. Ultrasonography showed increased thickness of the bladder wall with echogenic images and septations in the lumen.

The patient was treated with hyperhydration, thrombocyte replacement, and 2 doses of 2-mercapto-ethane sulfonate sodium. Intravenous immune globulin therapy (1 g/kg/d for 2 days) was given as an immunologic regulation therapy for the preliminary diagnosis of viral hemorrhagic cystitis. Hyperbaric oxygen therapy was planned because macroscopic hematuria persisted at 1 week after starting treatment. Polymerase chain reaction analysis for BK virus showed > 50 000 000 viral copies per mL in urine and no virus in blood. The patient received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres (90 minutes per daily treatment; 5 days per week), which was tolerated well. Macroscopic hematuria was decreased on the third day of hyperbaric oxygen therapy. Microscopic hematuria resolved completely at the end of the seventh day. The hemorrhagic cystitis did not recur during follow-up for 3 months. At 3 months, BK virus analysis showed no virus. At 6-month follow-up, the patient continued maintainance therapy and was in remission.

Hyperbaric oxygen therapy is the inhalation of 100% oxygen at supra-atmospheric ambient pressure, and it has a healing effect on necrotic or damaged tissues by increasing oxygenation and neova-scularization. Hyperbaric oxygen therapy has been used previously for BK virus-associated hemorrhagic cystitis after hematopoietic stem cell transplant, resulting in complete resolution in 94% patients.⁸ Hyperbaric oxygen therapy also has been used successfully for treatment of mucormycosis and leukoencephalopathy secondary to radiotherapy in leukemic patients.^9,10 Hyperbaric oxygen therapy also induces apoptosis in T-cell leukemia cell lines in vitro and may be an adjuvant treatment option in the future.¹¹

Hyperbaric oxygen therapy is a nontoxic, noninvasive, and cost-effective therapy compared with other treatment options for hemorrhagic cystitis. Although it may have limitations in treating BK virus-associated hemorrhagic cystitis, it may be a good option in resistant patients.

Volume: 12 Issue: 3 June 2014

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