title: Single-center Series of Bone Marrow Biopsy-Defined Large Granular Lymphocyte Leukemia: High Rates of Sustained Response to Oral Methotrexate.
abstract: Large granular lymphocyte (LGL) leukemia is a rare chronic lymphoproliferative disorder, with few large series reported to date. Series using stringent diagnostic criteria incorporating bone marrow biopsy (BMB), immunophenotyping, and T-cell receptor rearrangements are even scarcer.
  
  
  
  The present study was a single-center series of 39 patients with LGL leukemia diagnosed using immunohistochemical analysis of BMB samples and flow cytometric and molecular data.
  
  
  
  With a median follow-up of 3.2 years (range, 1.0-15.1 years), 15 patients (38%) never required treatment. Of the remaining 24 patients requiring treatment, 13 were initially treated with prednisolone, for an overall response rate (ORR) of 84.6% and a median duration of response (DOR) of 13.5 months (range, 5.7-70.3 months). Of the 24 patients, 9 received oral low-dose weekly methotrexate as first-line therapy, with 8 (89%) achieving a hematologic response and a median DOR of 132.7 months (range, 6.7-180.5 months). Another 5 patients received methotrexate after prednisolone failure; all 5 responded, with a median DOR of 14 months (range, 4-96 months). Only 2 patients developed progression during methotrexate therapy, and 4 patients experienced responses lasting ≥ 5 years.
  
  
  
  Single-agent oral methotrexate appears to be highly efficacious, resulting in long response durations and minimal toxicity.
authors.affiliation: Department of Clinical Hematology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom. Electronic address: tmunir@nhs.net.
authors.forename: Talha
authors.initials: T
authors.lastname: Munir
authors.affiliation: Department of Clinical Hematology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bishton
authors.affiliation: Department of Molecular Diagnostics, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Carter
authors.affiliation: Department of Clinical Hematology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: McMillan
authors.affiliation: Department of Histopathology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: O'Connor
authors.affiliation: Department of Histopathology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Sovani
authors.affiliation: Department of Clinical Hematology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Haynes
authors.affiliation: Department of Clinical Hematology, Nottingham University Hospitals National Health Services Trust, Nottingham, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Fox
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D054066:Leukemia, Large Granular Lymphocytic / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate
keywords: Cyclophosphamide; Cyclosporine; LGL leukemia; Methotrexate; Prednisolone