Research Papers:

Methotrexate therapy of T-cell large granular lymphocytic leukemia impact of STAT3 mutation

Zhi-Yuan Qiu, Lei Fan, Rong Wang, Robert Peter Gale, Hua-Jin Liang, Man Wang, Li Wang, Yu-Jie Wu, Chun Qiao, Yao-Yu Chen, Wei Xu, Jun Qian and Jian-Yong Li _

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Oncotarget. 2016; 7:61419-61425. https://doi.org/10.18632/oncotarget.11360

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Zhi-Yuan Qiu1,2, Lei Fan1, Rong Wang1, Robert Peter Gale3, Hua-Jin Liang1, Man Wang1, Li Wang1, Yu-Jie Wu1, Chun Qiao1, Yao-Yu Chen1, Wei Xu1, Jun Qian4, Jian-Yong Li1

1Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China

2Department of Oncology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

3Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom

4Department of Hematology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

Correspondence to:

Wei Xu, email: [email protected]

Jian-Yong Li, email: [email protected]

Jun Qian, email: [email protected]

Keywords: T-cell large granular lymphocytic leukemia, methotrexate, STAT3

Received: February 05, 2016     Accepted: August 09, 2016     Published: August 17, 2016


T-cell large granular lymphocytic leukemia (T-LGLL) is a rare haematologic neoplasm. Consequntly, there are no large prospective studies of therapy and no uniform therapy recommendations. We analyzed data from 36 subjects receiving methotrexate alone (N = 27) or with prednisone (N = 9) as initial therapy. 31 subjects responded (86%, 95% confidence interval [CI], 73, 95%) with 8 complete responses and 23 partial responses. Median time-to-response was 3 months (range, 1–5 months). Median response duration was 20 months (range, 2–55 months). β2-microoglobulin (β2-MG) and erythrocyte sedimentation rate (ESR) decreased significantly post-therapy (P < 0.0001). Pure red cell aplasia (PRCA) was present in 18 subjects (50%) of our subjects and responded well to methotrexate. 26 subjects (72%) were tested for STAT3 mutation. 9 with a mutation had a median treatment-free survival of 5 months (range, 0.5–13 months), significantly briefer than that of 17 subjects without a STAT3 mutation (19 months, range, 3–97 months; P = 0.012; log-rank test). Methotrexate with or without prednisone is an effective initial therapy of persons with T-LGLL with wild-type STAT3.

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