Influence of oral beclomethasone dipropionate on early non-infectious pulmonary outcomes after allogeneic hematopoietic cell transplantation: results from two randomized trials.
Early non-infectious pulmonary complications represent a significant cause of mortality after hematopoietic cell transplantation (HCT). We tested the hypothesis that oral beclomethasone dipropionate (BDP) is effective for preventing early non-infectious pulmonary complications after allogeneic HCT. We retrospectively reviewed the medical records of 120 patients, 60 in each treatment arm, to identify non-infectious and infectious pulmonary events and pulmonary function test results from all patients who participated in two randomized trials of oral BDP for treatment of acute gastrointestinal GVHD. 17-Beclomethasone monopropionate (17-BMP), the active metabolite of BDP, was evaluated in blood from the right atrium in four patients. Thirty-three of 42 (79%) placebo-treated patients experienced a decrease of the DL(CO) from pretransplant to day 80 after transplant, compared with 27 of 49 (55%) BDP-treated patients (P=0.02). In the first 200 days after randomization, there were no cases of non-infectious pulmonary complications in BDP-treated patients, vs four cases among placebo-treated patients (P=0.04). Levels of 17-BMP were detected in atrial blood at steady state. Delivery of a potent glucocorticoid such as 17-BMP to the pulmonary artery after oral dosing of BDP may be useful in modulating pulmonary inflammation and preventing the development of non-infectious pulmonary complications after allogeneic HCT.
Chien
J W
JW
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA. jchien@fhcrc.org
Sakai
M
M
Gooley
T A
TA
Schoch
H G
HG
McDonald
G B
GB
D000293:Adolescent; D000368:Aged; D001507:Beclomethasone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy*; D008172:Lung Diseases, Fungal / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests
C065857:beclomethasone 17-monopropionate; D001507:Beclomethasone