title: T-cell large granular lymphocyte leukemia: A report on the treatment of 29 patients and a review of the literature.
abstract: BACKGROUND
  To the authors' knowledge, there is no standard treatment for patients with T-cell large granular lymphocyte (LGL) leukemia. Available data are limited by patient numbers and coexisting pathologies.
  
  
  METHODS
  The authors report on the use of immunosuppressants (cyclosporin A [CSA] and low-dose oral methotrexate [MTX] given continuously) and cytotoxic agents in the treatment of 29 patients with T-cell LGL leukemia age over the past 20 years.
  
  
  RESULTS
  The overall response rate (ORR) to MTX (n = 8 patients) was 85.7% (complete hematologic response [CHR] rate, 14.3%; partial response [PR] rate, 71.4%) with dose-dependent responses observed and safe usage of doses >10 mg/m2 per week in 2 patients. The ORR to CSA (n = 23 patients) was 78.2% (CHR rate, 30.4%; PR rate, 47.8%). The median time to response for both agents was 1 month. Toxicity, although it was minor in most patients and was more common in the CSA group, included second malignancies in 5 patients. An ORR of 67% (all CHR) was attained with pentostatin (n = 4 patients); recurrences developed after a median of 4.6 years. Successful retreatment with pentostatin was possible but with increasing drug resistance. Cyclophosphamide induced CHR that lasted >7 years with bone marrow clearance in 1 of 4 patients. Alemtuzumab induced a PR in 1 patient who had refractory disease.
  
  
  CONCLUSIONS
  Both MTX and CSA were efficacious in the treatment of T-cell LGL leukemia but generally required long-term maintenance therapy. The authors highlight the risks of second malignancies and persistence of bone marrow disease. Although MTX and CSA were effective as first-line therapy, alemtuzumab and pentostatin merit further investigation, particularly for refractory disease.
authors.affiliation: Section of Haemato-oncology, Institute of Cancer Research, London, United Kingdom. nnenna.osuji@icr.ac.uk
authors.forename: Nnenna
authors.initials: N
authors.lastname: Osuji
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Geir
authors.initials: G
authors.lastname: Tjonnfjord
authors.forename: Henri
authors.initials: H
authors.lastname: Grech
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: John G
authors.initials: JG
authors.lastname: Swansbury
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D019992:Databases as Topic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015649:Pentostatin / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D015649:Pentostatin; D016572:Cyclosporine; D003520:Cyclophosphamide; D008727:Methotrexate