Immunosuppressive therapy of LGL leukemia: Prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998) Journal Article
| Authors: | Loughran, T. P.; Zickl, L.; Olson, T. L.; Wang, V.; Zhang, D.; Rajala, H. L. M.; Hasanali, Z.; Bennett, J. M.; Lazarus, H. M.; Litzow, M. R.; Evens, A. M.; Mustjoki, S.; Tallman, M. S. |
| Article Title: | Immunosuppressive therapy of LGL leukemia: Prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998) |
| Abstract: | Failure to undergo activation-induced cell death due to global dysregulation of apoptosis is the pathogenic hallmark of large granular lymphocyte (LGL) leukemia. Consequently, immunosuppressive agents are rational choices for treatment. This first prospective trial in LGL leukemia was a multicenter, phase 2 clinical trial evaluating methotrexate (MTX) at 10 mg/m 2 orally weekly as initial therapy (step 1). Patients failing MTX were eligible for treatment with cyclophosphamide at 100 mg orally daily (step 2). The overall response in step 1 was 38% with 95% confidence interval (CI): 26 and 53%. The overall response in step 2 was 64% with 95% CI: 35 and 87%. The median overall survival for patients with anemia was 69 months with a 95% CI lower bound of 46 months and an upper bound not yet reached. The median overall survival for patients with neutropenia has not been reached 13 years from study activation. Serum biomarker studies confirmed the inflammatory milieu of LGL but were not a priori predictive of response. We identify a gene expression signature that correlates with response and may be STAT3 mutation driven. Immunosuppressive therapies have efficacy in LGL leukemia. Gene signature and mutational profiling may be an effective tool in determining whether MTX is an appropriate therapy. © 2015 Macmillan Publishers Limited. |
| Keywords: | adult; cancer survival; controlled study; gene mutation; major clinical study; overall survival; prednisone; fatigue; neutropenia; drug dose reduction; drug withdrawal; gastrointestinal hemorrhage; cancer patient; methotrexate; follow up; prospective study; biological marker; stat3 protein; cancer immunotherapy; low drug dose; infection; multiple cycle treatment; phase 2 clinical trial; gene expression; anemia; fas ligand; vascular cell adhesion molecule 1; cyclophosphamide; drug screening; aspartate aminotransferase blood level; dyspnea; hyperglycemia; pneumonia; hypoxia; hyponatremia; survival time; multicenter study; myc protein; drug response; patient compliance; rheumatoid arthritis; upregulation; immunosuppressive treatment; melena; drug treatment failure; cytopenia; oxidative phosphorylation; transcription factor e2f1; intercellular adhesion molecule 1; lung infiltrate; purine; interleukin 18; respiratory chain; microrna 223; medication compliance; human; male; female; priority journal; article; large granular lymphocyte leukemia; purine metabolism |
| Journal Title: | Leukemia |
| Volume: | 29 |
| Issue: | 4 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-04-01 |
| Start Page: | 886 |
| End Page: | 894 |
| Language: | English |
| DOI: | 10.1038/leu.2014.298 |
| PROVIDER: | scopus |
| PMCID: | PMC4377298 |
| PUBMED: | 25306898 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
