Seminars in Hematology
Volume 40, Issue 3 , Pages 185-195 , July 2003

Clinical features of large granular lymphocyte leukemia

  • Thierry Lamy

      Affiliations

    • *Address correspondence to Thierry Lamy, MD, PhD, Department of Hematology, Service d’Hématologie, Hôpital Pontchaillou, CHU de Rennes, 35033, Rennes, France
    • Department of Hematology, Pontchaillou University Hospital, Rennes, France
    • ,
  • Thomas P. Loughran Jr

      Affiliations

    • Hematologic Malignancies Program, Department of Interdisciplinary-Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

References 

  1. Bassan R, Pronesti M, Buzzetti M, et al.  Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells. Cancer. 1989;63:90–95
  2. Battiwalla M, Sauntharajah Y, Nakamura R, et al.  Treatment of T-LGL (large granular lymphocytic disease) with cyclosporine A. Long term follow-up. Blood. 2002;100:669a; abstr
  3. Bennet JM, Catovsky D, Daniel MT, et al.  1989 Proposals for the classification of chronic (mature) B and T lymphoid leukemias: French-American-British (FAB) cooperative group. J Clin Oncol. 1989;42:567–584
  4. Bigouret V, Hoffman T, Arlettaz L, et al.  Monoclonal T cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94-NKG2C/E and NKD2D killer cell receptors. Blood. 2003;101:3198–3204
  5. Bleesing JJ, Janik JE, Fleisher TA. Common expression of an unusual CD45 isoform on T cells from patients with large granular lymphocyte leukaemia and autoimmune lymphoproliferative syndrome. Br J Haematol. 2003;120:93–96
  6. Bowman SJ, Sivakumaran M, Snowden N, et al.  The large granular lymphocyte syndrome with rheumatoid arthritis: Immunogenetic evidence for a broader definition of Felty’s syndrome. Arthritis Rheum. 1994;37:1326–1330
  7. Davey MP, Starkebaum G, Loughran TP. CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor Vβ genes. Blood. 1995;85:146–150
  8. Der Simonian H, Sugita M, Glass DN, et al.  Clonal Vα12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients. J Exp Med. 1993;177:1623–1631
  9. Dhodapkar MV, Li CY, Lust JA, et al.  Clinical spectrum of clonal proliferations of T-large granular lymphocytes: A T-cell clonopathy of undetermined significance?. Blood. 1994;84:1620–1627
  10. Ditzel HJ, Masaki Y, Nielsen H, et al.  Cloning and expression of a novel human antibody-antigen pair associated with Felty’s syndrome. Proc Natl Acad Sci USA. 2000;97:9234–9239
  11. Dolstra H, Preijers F, Van de Wiehl-Van Kemenade E, et al.  Expansion of CD8+ CD57+ T cells after allogeneic BMT is related with a low incidence of relapse and with cytomegalovirus infection. Br J Haematol. 1995;90:300–307
  12. Fehrer O, Barilla D, Locker J, et al.  T-cell large granular lymphocytic leukemia following orthotopic liver transplantation. Am J Hematol. 1995;49:216–220
  13. Gabor EP, Mishalani S, Lee S. Rapid response to cyclosporine therapy and sustained remission in large granular lymphocyte leukemia. Blood. 1996;87:1199–1200
  14. Genestier L, Paillot R, Fournel S, et al.  Immunosuppressive properties of methotrexate: Apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102:322–328
  15. Gentile TC, Uner AH, Hutchinson RE, et al.  CD3+ CD56+ aggressive variant of large granular lymphocyte leukemia. Blood. 1994;84:2315–2321
  16. Gentile TC, Wener MH, Starkebaum G, et al.  Humoral immune abnormalities in T-cell large granular lymphocyte leukemia. Leuk Lymphoma. 1996;23:365–370
  17. Gentile TC, Loughran TP. Resolution of autoimmune hemolytic anemia following splenectomy in CD3+ large granular lymphocyte leukemia. Leuk Lymphoma. 1996;23:405–408
  18. Gentile TC, Uner AH, Hutchinson RE, et al.  Large granular lymphocyte leukemia occurring after renal transplantation. Br J Haematol. 1998;101:507–512
  19. Gonzales-Chambers R, Przepiorka D, Winkelstein A, et al.  Lymphocyte subsets associated with T cell receptor beta-chain gene rearrangement in patients with rheumatoid arthritis and neutropenia. Arthritis Rheum. 1992;35:516–520
  20. Gorochov G, Debre P, Leblond V, et al.  Oliglonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor β chain variability after bone marrow transplantation. Blood. 1994;83:587–595
  21. Hamidou AM, Firouze BS, Lamy T, et al.  Low-dose methotrexate for the treatment of patients with large granular lymphocyte leukemia associated with rheumatoid arthritis. Am J Med. 2000;108:730–732
  22. Hanada T, Ishida T, Kojima H, et al.  Granular lymphocyte leukemia in association with multiple myeloma. Br J Haematol. 1992;80:127–129
  23. Harris NL, Jaffe ES, Diebold J, et al.  World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting-Airlie House, Virginia. J Clin Oncol. 1999;17:3835–3849
  24. Kanchan K, Loughran TP. Antigen-driven clonal T cell expansion in disorders of hematopoiesis. Leuk Res. 2003;27:291–292
  25. Kasten-Sportes C, Zaknoen S, Streis RG, et al.  T-cell receptor gene rearrangement in T-cell large granular leucocyte leukemia: Preferential Vα but diverse Jα usage in one of five patients. Blood. 1994;83:767–775
  26. Kawa-Ha K, Ishihara S, Ninomiya T, et al.  CD3− negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA. J Clin Invest. 1989;84:51–55
  27. Kothapalli R, Bailey RD, Kusmartseva I, et al.  Constitutive expression of cytotoxic proteases and down-regulation of protease inhibitors in LGL leukemia. Int J Oncol. 2003;22:33–39
  28. Kouides PA, Rowe JM. Large granular lymphocyte leukemia presenting with both amegakaryocytic thrombocytopenic purpura and pure red cell aplasia. Am J Hematol. 1995;49:232–236
  29. Kwong YL, Wong KF, Chan LC, et al.  Large granular lymphocyte leukemia: A study of nine cases in a Chinese population. Am J Clin Pathol. 1995;103:76–81
  30. Lacy MQ, Kurtin PJ, Tefferi A, et al.  Pure red cell aplasia: Association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities. Blood. 1996;87:3000–3006
  31. Lamy T, Bauer FA, Liu JH, et al.  Pathological role of Fas Ligand in aggressive LGL leukemia. Br J Haematol. 1998;108:717–723
  32. Lamy T, Amiot L, Drenou B, et al.  Response to granulocyte-macrophage colony stimulating factor (GM-CSF) but not to G-CSF in a case of agranulocytosis with large granular lymphocyte leukemia. Blood. 1994;84:2164
  33. Lamy T, Drenou D, Fardel O, et al.  Multidrug resistance analysis in lymphoproliferative disease of large granular lymphocytes. Br J Haematol. 1998;100:509–815
  34. Lamy T, Liu JH, Landowski T, et al.  Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3+ LGL leukemia. Blood. 1999;12:4771–4777
  35. Lamy T, Loughran TP. Current concepts: large granular lymphocyte leukemia. Blood Rev. 1999;13:230–240
  36. Langerak AW, van Den Beemd R, Wolvers-Tettero IL, et al.  Molecular and flow cytometric analysis of the Vbeta repertoire for clonality assessment in mature TCR alpha T-cell proliferations. Blood. 2001;98:165–173
  37. Lauria F, Foa R, Mogone N, et al.  Heterogeneity of large granular lymphocyte proliferations: Morphological, immunological, and molecular analysis in seven patients. Br J Haematol. 1987;66:187–191
  38. Lesveve JF, Feugier P, Lamy T, et al.  Association of B-chronic lymphocytic leukemia and T-large granular lymphocyte leukemia. Clin Lab Haematol. 2000;22:121–122
  39. Lima M, Almeida J, Santos AH, et al.  Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+) /TCR-alphabeta(+) large granular lymphocyte: Utility in assessing clonality and insights into the pathogenesis of the disease. Am J Pathol. 2001;159:1861–1868
  40. Liu JH, Wei S, Lamy T, et al.  Chronic neutropenia mediated by Fas-ligand. Blood. 2000;95:3219–3222
  41. Liu JH, Wei S, Lamy T, et al.  Blockade of fas dependent apoptosis by soluble Fas in LGL leukemia. Blood. 2002;100:1449–1453
  42. Loughran TP. Clonal diseases of large granular lymphocytes. Blood. 1993;82:1–4
  43. Loughran TP, Clark EA, Price TH, et al.  Adult onset cyclic neutropenia is associated with increased large granular lymphocytes. Blood. 1986;68:1082–1087
  44. Loughran TP, Kadin ME, Starkebaum G, et al.  Leukemia of large granular lymphocytes: Association with clonal chromosomal abnormalities and auto-immune neutropenia, thrombocytopenia and hemolytic anemia. Ann Intern Med. 1985;102:169–175
  45. Loughran TP, Kidd PG, Starkebaum G. Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood. 1994;84:2164–2170
  46. Loughran TP, Hadlock KG, Yang Q, et al.  Seroreactivity to an envelope protein of human T-cell leukemia/lymphoma virus in patients with CD3− (NK) lymphoproliferative disease of granular lymphocytes. Blood. 1997;90:1981–1997
  47. Loughran TP, Hadlock KG, Perzova R, et al.  Epitope mapping of HTLV envelope seroreactivity in LGL leukemia. Br J Haematol. 1998;101:318–324
  48. Makishima H, Ishida F, Ito T, et al.  DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes. Br J Haematol. 2002;118:462–469
  49. Man C, Au WY, Pang A, et al.  Deletion 6q as a recurrent chromosomal aberration in T-cell large granular lymphocyte leukemia. Cancer Genet Cytogenet. 2002;139:71–74
  50. Marlton P, Taylor K, Elliott S, et al.  Monoclonal large granular lymphocyte proliferation in SLE with HTLV-I seroreactivity. Aust NZ J Med. 1992;22:54–55
  51. Matrai Z, Lelkes G, Milosevits J, et al.  T-cell large granular lymphocytic leukemia associated with red cell aplasia, successfully treated with cyclophosphamide. Orv Hetil. 1997;138:2075–2080
  52. Molitor JL, Saint-Louis J, Louvet C, et al.  Large granular lymphocytic leukemia disclosed by bilateral uveitis: Association with celiac disease. Rev Med Intern. 1997;18:237–239
  53. Morice WG, Kurtin PJ, Tefferi A, et al.  Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxydase for CD8, TIA-1, and granzyme. Blood. 2002;99:268–274
  54. Morikawa K, Oseko F, Hara J, et al.  Functional analysis of clonally expanded CD8, TCR γδ T cells in a patient with chronic T-gamma lymphoproliferative disease. Leuk Res. 1990;14:581–592
  55. Morley JK, Batliwalla FM, Hinorani R, et al.  Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. J Immunol. 1995;154:6182–6190
  56. Mothy M, Faucher C, Vey N, et al.  Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: A long-term analysis. Leukemia. 2002;16:2129–2133
  57. Oshimi K, Shinkai Y, Okumura K, et al.  Perforin gene expression in granular lymphocyte proliferative disorders. Blood. 1990;75:704–708
  58. Oshimi K, Yamada O, Kanako T, et al.  Laboratory findings and clinical courses of 33 patients with large granular lymphocyte proliferative disorders. Leukemia. 1993;7:782–788
  59. Pandolfi F, Loughran TP, Starkebaum G, et al.  Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study. Cancer. 1990;65:341–348
  60. Papadaki T, Stamopoulos K, Kosmas C, et al.  Clonal T-large granular lymphocyte proliferations associated with clonal B cell lymphoproliferative disorders: Report of eight cases. Leukemia. 2002;16:2167–2169
  61. Papadaki T, Stamopoulos K, Kosmas C, et al.  A unique case of splenic zone-cell lymphoma with synchronous clonal T-cell large granular lymphocyte proliferation: An immunologic, immunohistochemical and genotypic study. Leuk Res. 2003;27:85–87
  62. Persova R, Loughran TP. Constitutive expression of Fas ligand in large granular lymphocytes leukaemia. Br J Haematol. 1997;97:123–126
  63. Posnett DN, Sinha R, Kabak S, et al.  Clonal populations of T cells in normal elderly humans: The T cell equivalent to benign monoclonal gammapathy. J Exp Med. 1994;179:609–618
  64. Rodriguez A, Yood RA, Condon TJ, et al.  Recurrent uveitis in a patient with adult onset cyclic neutropenia associated with increased large granular lymphocytes. Br J Ophthalmol. 1997;81:415
  65. Rossof LJ, Genovese J, Coleman M, et al.  Primary pulmonary hypertension in a patient with CD8/T-cell large granular lymphocyte. Chest. 1997;112:551–553
  66. Saitoh T, Karasawa M, Sakuraya M, et al.  Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: The serum level of Fas ligand is a marker of LGL leukemia activity. Eur J Haematol. 2000;65:272–275
  67. Sampalo LA, Lopez-Gomez M, Jimenez-Alonso J. Proliferation of large granular lymphocytes in patients with systemic lupus erythematosus. Rev Clin Esp. 1995;195:373–379
  68. Saunthararajah Y, Molldrem JL, Rivera M, et al.  Coincident myelodysplastic syndrome and T-cell large granular lymphocyte disease: Clinical and pathophysiological features. Br J Haematol. 2001;112:195–200
  69. Semenzato G, Pandolfi F, Chiesesi T, et al.  The lymphoproliferative disease of granular lymphocytes. A heterogeneous disorder ranging from indolent to aggressive conditions. Cancer. 1987;60:2971–2978
  70. Semenzato G, Zambello R, Starkebaum G, et al.  The lymphoproliferative disease of granular lymphocytes: Updated criteria for diagnosis. Blood. 1997;89:256–260
  71. Shvidel L, Duksin C, Tzimanis A, et al.  Cytokine release by activated T-cells in large granular lymphocytic leukemia associated with autoimmune disorders. Hematol J. 2002;3:32–37
  72. Sood R, Stewart CC, Aplan PD, et al.  Neutropenia associated with T-cell large granular lymphocyte leukemia: Long-term response to cyclosporine therapy despite persistence of abnormal cells. Blood. 1998;91:3372–3378
  73. Starkebaum G, Loughran TP, Gaur LK, et al.  Immunogenetic similarities between patients with Felty’s syndrome and those with clonal expansions of large granular lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1997;40:624–626
  74. Suzushima H, Asou N, Eto K, et al.  CD4+ CD8+ granular lymphocytic leukemia arising in a patient with acute myeloblastic leukemia. Leukemia. 1994;8:1884–1889
  75. Takeuchi M, Tamaoki A, Soda R, et al.  Spontaneous remission of large granular lymphocyte T-cell leukemia. Leukemia. 1999;13:313–314
  76. Taniwaki M, Tagawa S, Nishigaki H, et al.  Chromosomal abnormalities define clonal proliferation in CD3− large granular lymphocyte leukemia. Am J Hematol. 1990;33:32–38
  77. Tefferi A, Li CY, Witzig TE, et al.  Chronic natural killer cell lymphocytosis: A descriptive clinical study. Blood. 1994;84:2721–2725
  78. Wong KF, Chan JCW, Liu HSY, et al.  Chromosomal abnormalities in T-cell large granular lymphocyte leukemia: Report of two cases and review of the literature. Br J Haematol. 2002;116:598–600
  79. Yoe J, Gause BL, Curti BD, et al.  Development of rheumatoid arthritis after treatment of large granular lymphocyte leukemia with deoxycoformycin. Am J Hematol. 1998;57:253–257
  80. Zambello R, Trentin L, Facco M, et al.  Analysis of the T cell receptor in the lymphoproliferative disease of granular lymphocytes: Superantigen activation of clonal CD3+ granular lymphocytes. Cancer Res. 1995;55:6140–6145

PII: S0037-1963(03)00133-1

Seminars in Hematology
Volume 40, Issue 3 , Pages 185-195 , July 2003

Article Tools

* Image Usage & Resolution