Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans

A Pilot Study Evaluating the Efficacy of Azithromycin, N-acetylcystein and Inhaled Corticosteroid Combination Therapy for Bronchiolitis Obliterans After Allogeneic Hematopoietic Cell Transpantation

[Study Objectives]

• To evaluate the efficacy of azithromycin, N-acetylcystein, and inhaled corticosteroid combination therapy in patients with bronchiolitis obliterans as a complication of allogeneic hematopoietic cell transplantation in terms of response rate at 6 months after treatment initiation based on the improvement of FEV1.

• Bronchiolitis obliterans (BO) is a graft-versus-host disease of respiratory organs.
• Prognosis of BO is very poor, and the overall outcome of patients who are involved in BO is very dismal.
• The mechanism of BO has been known to be associated with immune / non-immune response.
• Corticosteroid and immunosuppressants are recommended as a best current treatment options for BO, which have been not satisfactory.
• Many treatment options have been tried to improve the outcome of BO.
• Azithromycin, as an immune modulating agent, has been tried for the treatment of BO, and has been reported to show hopeful results.
• N-acetylcystein, as an antioxidative agent, has been tried for BO.
• Inhaled corticosteroid may help to improve airway inflammation and decrease the amount of systemic corticosteroid.
• These 3 drugs are widely used for other respiratory disease, have been proven to be safe, and have shown some efficacy for BO in various depth of evidence.
• In these rationale, we'd like to try the 3-drug combination for BO, to assess the efficacy and safety of these drug combination.

Inclusion Criteria:

• Patients who previously received allogeneic hematopoietic cell transplantation due to hematologic malignancy, bone marrow failure syndrome, and other compatible disease.
• Patients who are diagnosed as bronchiolitis obliterans (BO) according to the NIH diagnostic guideline which is suggested as below.
• Patients should be 15 years of age or older, but younger than 75 years.
• Patients should have estimated life expectancy of more than 3 months.
• Patients must have adequate hepatic function (bilirubin less than 3.0 ㎎/㎗, AST and ALT less than three times the upper normal limit).
• Patients must have adequate renal function (creatinine less than 2.0 ㎎/㎗).

Exclusion Criteria:

• Presence of significant active infection
• Presence of uncontrolled bleeding
• Any coexisting major illness or organ failure
• Patients with a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible.
• Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
• Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)