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

• Published in: Oncotarget Vol. 7; no. 38; pp. 61419 - 61425
• Main Authors: Qiu, Zhi-Yuan, Fan, Lei, Wang, Rong, Gale, Robert Peter, Liang, Hua-Jin, Wang, Man, Wang, Li, Wu, Yu-Jie, Qiao, Chun, Chen, Yao-Yu, Xu, Wei, Qian, Jun, Li, Jian-Yong
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.09.2016
• Subjects: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Agents, Hormonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Blood Sedimentation - drug effects; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leukemia, Large Granular Lymphocytic - blood; Leukemia, Large Granular Lymphocytic - drug therapy; Leukemia, Large Granular Lymphocytic - genetics; Leukemia, Large Granular Lymphocytic - mortality; Male; Methotrexate - therapeutic use; Middle Aged; Mutation; Prednisone - therapeutic use; Red-Cell Aplasia, Pure - drug therapy; Red-Cell Aplasia, Pure - etiology; Remission Induction - methods; Research Paper; Sequence Analysis, DNA; STAT3 Transcription Factor - genetics; Time Factors; Treatment Outcome; T-cell large granular lymphocytic leukemia; methotrexate; STAT3
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.11360

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.