1. A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.
- Author
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Tian XP, Su N, Wang L, Huang WJ, Liu YH, Zhang X, Huang HQ, Lin TY, Ma SY, Rao HL, Li M, Liu F, Zhang F, Zhong LY, Liang L, Lan XL, Li J, Liao B, Li ZH, Tang QL, Liang Q, Shao CK, Zhai QL, Cheng RF, Sun Q, Ru K, Gu X, Lin XN, Yi K, Shuang YR, Chen XD, Dong W, Sun C, Sang W, Liu H, Zhu ZG, Rao J, Guo QN, Zhou Y, Meng XL, Zhu Y, Hu CL, Jiang YR, Zhang Y, Gao HY, He WJ, Xia ZJ, Pan XY, Hai L, Li GW, Song LY, Kang TB, Xie D, and Cai QQ
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clinical Decision-Making methods, Disease-Free Survival, F-Box-WD Repeat-Containing Protein 7 genetics, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local prevention & control, Patient Selection, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma mortality, Predictive Value of Tests, Receptor, Notch1 genetics, Retrospective Studies, Risk Assessment methods, CpG Islands genetics, DNA Methylation, Neoplasm Recurrence, Local epidemiology, Nomograms, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens., Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort ( n = 160). The four-CpG classifier was validated in the internal testing cohort ( n = 68) and independent validation cohort ( n = 321)., Results: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk ( P < 0.001). This classifier also showed good predictive value in the internal testing cohort ( P < 0.001) and the independent validation cohort ( P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1 / FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation., Conclusions: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision., (©2020 American Association for Cancer Research.)
- Published
- 2020
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