title: Methotrexate therapy of T-cell large granular lymphocytic leukemia impact of STAT3 mutation.
abstract: 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.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.|Department of Oncology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Qiu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Hua-Jin
authors.initials: HJ
authors.lastname: Liang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Yao-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001799:Blood Sedimentation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D054066:Leukemia, Large Granular Lymphocytic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009154:Mutation; D011241:Prednisone / Q000627:therapeutic use; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy / Q000209:etiology; D012074:Remission Induction / Q000379:methods; D050796:STAT3 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D011241:Prednisone; D008727:Methotrexate
keywords: STAT3; T-cell large granular lymphocytic leukemia; methotrexate