Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage.