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Biol Blood Marrow Transplant. 2016 Apr;22(4):710-716. doi: 10.1016/j.bbmt.2015.10.009. Epub 2015 Oct 22.

Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.

Author information

1
Division of Blood and Marrow Transplantation, Children's Research Institute, Children's National Health System, Washington, DC; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: kmwillia@cnmc.org.
2
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Division of Medicine and Oncology, Washington University, Saint Louis, Missouri.
4
Division of Hematology/Oncology, Vandebilt University, Nashville, Tennessee.
5
Division of Hematology/Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota.
6
Division of Hematological Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts.
7
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida.
8
Division of Hematology/Oncology, Mayo Clinic- Scottsdale, Scottsdale, Arizona.
9
Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
10
Department of Medicine, Weill Cornell Medical College, New York, New York.
11
Gilead, Seattle, Washington.
12
Division of Blood and Marrow Transplantation, Children's Research Institute, Children's National Health System, Washington, DC.
13
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
14
Division of Hematopoietic stem cell transplantation, National Cancer Center Hospital, Tokyo, Japan.

Abstract

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

KEYWORDS:

Azithromycin; Bronchiolitis obliterans syndrome; Fluticasone; Hematopoietic cell transplantation; Leukotrienes; Lung chronic graft-versus-host disease; Montelukast

Comment in

PMID:
26475726
PMCID:
PMC4801753
DOI:
10.1016/j.bbmt.2015.10.009
[Indexed for MEDLINE]
Free PMC Article

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