Laboratory of Molecular Medicine, Department of Clinical Immunology-7631, University of Copenhagen, Denmark.
Biol Blood Marrow Transplant. 2011 Sep;17(9):1299-307. doi: 10.1016/j.bbmt.2011.01.008. Epub 2011 Jan 11.
Increased plasma concentrations of YKL-40, also called chitinase-3-like-1 protein (CHI3L1), have been correlated with disease severity in a variety of malignant and inflammatory diseases. The objective of the current study was to assess pretransplant recipient and donor CHI3L1 polymorphisms and plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had higher relapse-related mortality (33% versus 18%, P = .04; hazard ratio (HR) = 4.41, P = .01), lower progression-free survival (38% versus 64%, P < .01; HR = 2.84, P = .01), and overall survival (42% versus 69%, P = .01; HR = 3.09, P = .01). Recipients transplanted with donors with high YKL-40 concentrations had an increased probability and risk of grade 2-4 acute graft-versus-host disease (aGVHD) (93% versus 62%, P < .01; HR = 2.25, P = .02). CHI3L1 polymorphisms were associated with plasma YKL-40 concentrations, but not with clinical outcomes. In conclusion, our study suggests that plasma YKL-40 could function as a biomarker for relapse risk and treatment-related toxicity, and possibly as a tool complementing clinical risk scores such as the HCT comorbidity index.
YKL-40(也称为几丁质酶 3 样蛋白 1,CHI3L1)的血浆浓度升高与多种恶性和炎症性疾病的疾病严重程度相关。本研究的目的是评估非清髓性条件化造血细胞移植(HCT)治疗 149 例血液恶性肿瘤患者前接受者和供者 CHI3L1 多态性和血浆 YKL-40 浓度作为预后生物标志物。移植前 YKL-40 浓度高于年龄校正第 95 百分位数(高)的患者复发相关死亡率更高(33%比 18%,P =.04;危险比(HR)= 4.41,P =.01),无进展生存率更低(38%比 64%,P <.01;HR = 2.84,P =.01),总生存率更低(42%比 69%,P =.01;HR = 3.09,P =.01)。接受高 YKL-40 浓度供者移植的患者发生 2-4 级急性移植物抗宿主病(aGVHD)的概率和风险增加(93%比 62%,P <.01;HR = 2.25,P =.02)。CHI3L1 多态性与血浆 YKL-40 浓度相关,但与临床结局无关。总之,我们的研究表明,血浆 YKL-40 可能是复发风险和治疗相关毒性的生物标志物,并且可能是补充 HCT 合并症指数等临床风险评分的工具。