Medical Oncology

, Volume 27, Issue 2, pp 286–290 | Cite as

T-cell large granular lymphocytic (T-LGL) leukemia: a single institution experience

  • Aleksandra Sretenovic
  • Darko AnticEmail author
  • Snezana Jankovic
  • Mirjana Gotic
  • Maja Perunicic-Jovanovic
  • Ljubomir Jakovic
  • Biljana Mihaljevic
Original Paper


Background T-cell large granular lymphocytic (T-LGL) leukemia is a rare lymphoproliferative disease which usually affects elderly people. The clinical course of T-LGL leukemia is generally indolent, with lymphocytosis and splenomegaly in 20–50% patients, hepatomegaly in 5–20% of patients, and less commonly, lymphadenopathy. T-LGL leukemia is associated with immunological abnormalities: rheumatoid factor with or without rheumatoid arthritis (RA), Coombs positive hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), positive anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), hypogammaglobulinemia, and polyclonal hypergammaglobulinemia. Aim To compare clinical and laboratory features of T-LGL leukemia patients and their responses to different chemotherapy regimens. Methods Six patients (3 males and 3 females) with T-LGL leukemia were analyzed. The diagnosis was based on accepted morphologic criteria, immunophenotype, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangements. Results All patients exhibited lymphocytosis, mainly with unusual morphologies, splenomegaly, and elevated serum lactate dehydrogenase (LDH). Three patients were treated with a Fludarabine–Cyclophosphamide (FC) combination as initial therapy while three patients received CHOP. Two patients received more than one treatment regimen. One patient died due to T-LGL leukemia in first year after diagnosis, one patient died 4 years after diagnosis, two patients interrupted their treatment, and two patients are still alive. Conclusions Further prospective studies are needed for establishing a gold standard therapy for T-LGL leukemia.


T-cell leukemia Large granular lymphocytic leukemia T-LGL leukemia Clinical data Chemotherapy 


  1. 1.
    Chan WC, Catovsky D, Foucar K, Montserrat E. T-cell large granular lymphocyte leukaemia. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of hepatopoietic and lymphoid tissues. IARC: Lyon; 2001. p. 197–8.Google Scholar
  2. 2.
    Aribi A, et al. Experience in a single institution over 8 years. Leuk Res. 2007;31:939–45. doi: 10.1016/j.leukres.2006.09.003.CrossRefPubMedGoogle Scholar
  3. 3.
    Perzova R, Loughran TP Jr. Constitutive expression of Fas ligand in large granular lymphocyte leukaemia. Br J Haematol. 1997;97:123–6. doi: 10.1046/j.1365-2141.1997.d01-2113.x.CrossRefPubMedGoogle Scholar
  4. 4.
    Oshimi K, Shinkai Y, Okumura K, Oshimi Y, Mizoguchi H. Perforin gene expression in granular lymphocyte proliferative disorders. Blood. 1990;75:704–8.PubMedGoogle Scholar
  5. 5.
    Kothapalli R, et al. Constitutive expression of cytotoxic proteases and down regulation of protease inhibitors in LGL leukemia. Int J Oncol. 2003;22:33–9.PubMedGoogle Scholar
  6. 6.
    Loughran TP Jr, et al. Detection of human T cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia. Blood. 1992;80:1116–9.PubMedGoogle Scholar
  7. 7.
    Loughran TP Jr, et al. Epitope mapping of HTLV envelope seroreactivity in LGL leukaemia. Br J Haematol. 1998;101:318–24. doi: 10.1046/j.1365-2141.1998.00691.x.CrossRefPubMedGoogle Scholar
  8. 8.
    Greer JP, Kinney MC, Loughran Jr TP. T cell and NK cell lymphoproliferative disorders. Hematology Am Soc Hematol Educ Program 2001; 259–81. doi: 10.1182/asheducation-2001.1.259.
  9. 9.
    Sokol L, Loughran TP Jr. Large granular lymphocyte leukemia. Oncologist. 2006;11:263–73. doi: 10.1634/theoncologist.11-3-263.CrossRefPubMedGoogle Scholar
  10. 10.
    Dhodapkar M, Chin-Yang L, Lust J, Tefferi A, Phyliky RL. Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood. 1994;84:1620–7.PubMedGoogle Scholar
  11. 11.
    Loughran TP Jr, Kidd PG, Starkebaum G. Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood. 1994;84:2164–70.PubMedGoogle Scholar
  12. 12.
    Osuji N, et al. T-cell large granular lymphocyte leukemia: a report on the treatment of 29 patients and a review of the literature. Cancer. 2006;107:570–8. doi: 10.1002/cncr.22032.CrossRefPubMedGoogle Scholar
  13. 13.
    Tse E, et al. Fludarabine, mitoxantrone and dexamethasone as first-line treatment for T-cell large granular lymphocyte leukemia. Leukaemia. 2007;21(10):2225–6. doi: 10.1038/sj.leu.2404767.CrossRefGoogle Scholar
  14. 14.
    Kwong YL, Wong KF. Association of pure red cell aplasia with T large granular lymphocyte leukaemia. J Clin Pathol. 1998;51:672–5. doi: 10.1136/jcp.51.9.672.CrossRefPubMedGoogle Scholar
  15. 15.
    Sternberg A, et al. Neutropenia and anaemia associated with T-cell large granular lymphocyte leukaemia responds to fludarabine with minimal toxicity. Br J Haematol. 2003;120:699–701. doi: 10.1046/j.1365-2141.2003.04148.x.CrossRefPubMedGoogle Scholar
  16. 16.
    Ru X, Leibman HA. Successful treatment of refractory pure red cell aplasia associated with lymphoproliferative disorders with the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). Br J Haematol. 2003;123:278–81. doi: 10.1046/j.1365-2141.2003.04609.x.CrossRefPubMedGoogle Scholar
  17. 17.
    Rosenblum MD, et al. Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukaemia. Blood. 2004;103:1969–71. doi: 10.1182/blood-2003-11-3951.CrossRefPubMedGoogle Scholar
  18. 18.
    Osuji N. CD52 expression in T-cell large granular lymphocyte leukaemia—implications for treatment with alemtuzumab. Leuk Lymphoma. 2005;46:723–7. doi: 10.1080/10428190500052156.CrossRefPubMedGoogle Scholar
  19. 19.
    Ruskova A, Thula R, Chan G. Aggressive natural killer-cell leukemia: report of five cases and review of the literature. Leuk Lymphoma. 2004;45:2427–38. doi: 10.1080/10428190400004513.CrossRefPubMedGoogle Scholar
  20. 20.
    Battiwalla M, et al. HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders. Br J Haematol. 2003;123:449–53. doi: 10.1046/j.1365-2141.2003.04613.x.CrossRefPubMedGoogle Scholar
  21. 21.
    Matrai Z, Lelkes G, Milosevits J, Paldine HP, Pecze K. T-cell large granular lymphocytic leukemia associated with pure red cell aplasia, successfully treated with cyclophosphamide. Orv Hetil. 1997;138:2075–80. (Hungarian).PubMedGoogle Scholar
  22. 22.
    Langford CA, Klippel JH, Balow JE, James SP, Sneller MC. Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2. Inflammatory bowel disease and systemic vasculitis, and therapeutic toxicity. Ann Intern Med. 1998;129:49–58.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Aleksandra Sretenovic
    • 1
  • Darko Antic
    • 1
    Email author
  • Snezana Jankovic
    • 1
  • Mirjana Gotic
    • 1
  • Maja Perunicic-Jovanovic
    • 1
  • Ljubomir Jakovic
    • 1
  • Biljana Mihaljevic
    • 1
  1. 1.Institute of HematologyClinical Center SerbiaBelgradeSerbia

Personalised recommendations