Decreased Serum Levels of Clara Cell Secretory Protein (CC16) Are Associated with Bronchiolitis Obliterans and May Permit Early Diagnosis in Patients after Allogeneic Stem-Cell Transplantation


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Abstract

Background.Bronchiolitis obliterans (BO) is a common complication and is associated with high mortality after allogeneic stem-cell transplantation (SCT). Early diagnosis of BO may improve outcome. Low levels of Clara cell secretory protein (CC16) have previously been associated with BO in lung transplant recipients.Methods.Serum samples were collected from eight patients with BO, eight patients with chronic graft-versus-host disease (GVHD), and eight control patients with neither BO nor chronic GVHD in a matched patient analysis. Patients were matched for diagnosis, conditioning, donor match, and GVHD prophylaxis. Another seven patients with BO were also analyzed separately. CC16 was measured with an enzyme-linked immunosorbent assay method.Results.In the matched analysis, eight patients were diagnosed with BO at a median of 11.5 months (range, 4–13 months) after SCT and in nonmatched BO patients at a median of 12 months (range, 9–36 months). In the matched patient analysis, patients with BO had significantly lower (P=0.03) or decreasing (P=0.02) levels of CC16 compared with patients with only chronic GVHD or controls. In the matched patient analysis, measurement of CC16 showed a sensitivity of 88% and a specificity of 81%.With the criteria of low levels of CC16 or a decrease of more than 40% compared with the previous sample, BO was detected with analysis of CC16 in 13 of 15 patients. In 11 of the 13 patients, low or decreasing values of CC16 were detected at a median of 10 months (range, 1–30 months) before BO was diagnosed clinically.Conclusions.Low levels of CC16 are associated with BO after allogeneic SCT. Monitoring of CC16 in serum after SCT may have potential as an early marker for BO.

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