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Large Granular Lymphocyte Leukemia

  • Chapter
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Chronic Lymphocytic Leukemia

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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Abstract

Large granular lymphocyte leukemia (LGL-L) is a rare lymphoproliferative disorder characterized by the clonal expansion of mature post-thymic T- or natural killer (NK)-cells. The 2016 World Health Organization (WHO) classification of mature T- and NK-cell neoplasms recognizes three different subtypes including T-cell large granular lymphocyte leukemia (T-LGL-L), aggressive NK-cell leukemia (AKNL), and the provisional entity chronic lymphoproliferative disorder of NK (CLPD-NK) cells. The clinical presentation of LGL-L is dominated by neutropenia with recurrent infections, anemia, splenomegaly, and autoimmune manifestations. At the molecular level, constitutive activation of JAK/STAT signaling by recurrent gain-of-function mutations in STAT3 and STAT5B has recently been discovered and is now considered the key pathogenetic factor. Immunosuppressive therapy employing low-dose MTX, cyclophosphamide, and cyclosporine A remains the current standard of treatment. It is effective in correcting cytopenias in the majority of the patients but usually fails to eradicate the leukemic cell clone. Here, we discuss recent advances regarding the diagnostic workup, molecular pathogenesis, and treatment of this rare disease group.

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References

  1. Loughran TP Jr, Kadin ME, Starkebaum G, Abkowitz JL, Clark EA, Disteche C, et al. Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia. Ann Intern Med. 1985;102(2):169–75.

    Article  PubMed  Google Scholar 

  2. Swerdlow SH, Campo E, Harris NL. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Publications; 2008.

    Google Scholar 

  3. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. https://doi.org/10.1182/blood-2016-01-643569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lima M. Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis. Orphanet J Rare Dis. 2013;8:95. https://doi.org/10.1186/1750-1172-8-95.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lamy T, Moignet A, Loughran TP Jr. LGL leukemia: from pathogenesis to treatment. Blood. 2017;129(9):1082–94. https://doi.org/10.1182/blood-2016-08-692590.

    Article  CAS  PubMed  Google Scholar 

  6. Lamy T, Loughran TP Jr. How I treat LGL leukemia. Blood. 2011;117(10):2764–74. https://doi.org/10.1182/blood-2010-07-296962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shah MV, Hook CC, Call TG, Go RS. A population-based study of large granular lymphocyte leukemia. Blood Cancer J. 2016;6(8):e455. https://doi.org/10.1038/bcj.2016.59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dinmohamed AG, Brink M, Visser O, Jongen-Lavrencic M. Population-based analyses among 184 patients diagnosed with large granular lymphocyte leukemia in the Netherlands between 2001 and 2013. Leukemia. 2016;30(6):1449–51. https://doi.org/10.1038/leu.2016.68.

    Article  CAS  PubMed  Google Scholar 

  9. Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, et al. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica. 2010;95(9):1534–41. https://doi.org/10.3324/haematol.2009.018481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Suzuki R, Suzumiya J, Nakamura S, Aoki S, Notoya A, Ozaki S, et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia. 2004;18(4):763–70. https://doi.org/10.1038/sj.leu.2403262.

    Article  CAS  PubMed  Google Scholar 

  11. Mohan SR, Maciejewski JP. Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia. Curr Opin Hematol. 2009;16(1):27–34. https://doi.org/10.1097/MOH.0b013e32831c8407.

    Article  CAS  PubMed  Google Scholar 

  12. Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood. 1997;89(1):256–60.

    CAS  PubMed  Google Scholar 

  13. Oshimi K. Leukemia and lymphoma of natural killer lineage cells. Int J Hematol. 2003;78(1):18–23.

    Article  PubMed  Google Scholar 

  14. Tanahashi T, Sekiguchi N, Matsuda K, Takezawa Y, Ito T, Kobayashi H, et al. Cell size variations of large granular lymphocyte leukemia: implication of a small cell subtype of granular lymphocyte leukemia with STAT3 mutations. Leuk Res. 2016;45:8–13. https://doi.org/10.1016/j.leukres.2016.04.001.

    Article  CAS  PubMed  Google Scholar 

  15. Lundell R, Hartung L, Hill S, Perkins SL, Bahler DW. T-cell large granular lymphocyte leukemias have multiple phenotypic abnormalities involving pan-T-cell antigens and receptors for MHC molecules. Am J Clin Pathol. 2005;124(6):937–46.

    Article  CAS  PubMed  Google Scholar 

  16. Yabe M, Medeiros LJ, Wang SA, Konoplev S, Ok CY, Loghavi S, et al. Clinicopathologic, immunophenotypic, cytogenetic, and molecular features of gammadelta T-cell large granular lymphocytic leukemia: an analysis of 14 patients suggests biologic differences with alphabeta T-cell large granular lymphocytic leukemia. [corrected]. Am J Clin Pathol. 2015;144(4):607–19. https://doi.org/10.1309/AJCPJSA1E1YWSZEY.

    Article  CAS  PubMed  Google Scholar 

  17. Rajala HL, Eldfors S, Kuusanmaki H, van Adrichem AJ, Olson T, Lagstrom S, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541–50. https://doi.org/10.1182/blood-2012-12-474577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hsieh YC, Chang ST, Huang WT, Kuo SY, Chiang TA, Chuang SS. A comparative study of flow cytometric T cell receptor Vbeta repertoire and T cell receptor gene rearrangement in the diagnosis of large granular lymphocytic lymphoproliferation. Int J Lab Hematol. 2013;35(5):501–9. https://doi.org/10.1111/ijlh.12041.

    Article  PubMed  Google Scholar 

  19. Lima M, Almeida J, Santos AH, dos Anjos Teixeira M, Alguero MC, Queiros ML, et al. Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease. Am J Pathol. 2001;159(5):1861–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Epling-Burnette PK, Painter JS, Chaurasia P, Bai F, Wei S, Djeu JY, et al. Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes. Blood. 2004;103(9):3431–9. https://doi.org/10.1182/blood-2003-02-0400.

    Article  CAS  PubMed  Google Scholar 

  21. Fischer L, Hummel M, Burmeister T, Schwartz S, Thiel E. Skewed expression of natural-killer (NK)-associated antigens on lymphoproliferations of large granular lymphocytes (LGL). Hematol Oncol. 2006;24(2):78–85. https://doi.org/10.1002/hon.777.

    Article  CAS  PubMed  Google Scholar 

  22. Epling-Burnette PK, Liu JH, Catlett-Falcone R, Turkson J, Oshiro M, Kothapalli R, et al. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest. 2001;107(3):351–62. https://doi.org/10.1172/JCI9940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jerez A, Clemente MJ, Makishima H, Koskela H, Leblanc F, Peng Ng K, et al. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood. 2012;120(15):3048–57. https://doi.org/10.1182/blood-2012-06-435297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Andersson E, Kuusanmaki H, Bortoluzzi S, Lagstrom S, Parsons A, Rajala H, et al. Activating somatic mutations outside the SH2-domain of STAT3 in LGL leukemia. Leukemia. 2016;30(5):1204–8. https://doi.org/10.1038/leu.2015.263.

    Article  CAS  PubMed  Google Scholar 

  25. Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmaki H, Andersson EI, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366(20):1905–13. https://doi.org/10.1056/NEJMoa1114885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;19(21):2468–73. https://doi.org/10.1038/sj.onc.1203476.

    Article  CAS  PubMed  Google Scholar 

  27. Andersson EI, Tanahashi T, Sekiguchi N, Gasparini VR, Bortoluzzi S, Kawakami T, et al. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. Blood. 2016;128(20):2465–8. https://doi.org/10.1182/blood-2016-06-724856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Morice WG, Kurtin PJ, Tefferi A, Hanson CA. Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B. Blood. 2002;99(1):268–74.

    Article  CAS  PubMed  Google Scholar 

  29. Osuji N, Beiske K, Randen U, Matutes E, Tjonnfjord G, Catovsky D, et al. Characteristic appearances of the bone marrow in T-cell large granular lymphocyte leukaemia. Histopathology. 2007;50(5):547–54. https://doi.org/10.1111/j.1365-2559.2007.02656.x.

    Article  CAS  PubMed  Google Scholar 

  30. Burks EJ, Loughran TP Jr. Pathogenesis of neutropenia in large granular lymphocyte leukemia and Felty syndrome. Blood Rev. 2006;20(5):245–66. https://doi.org/10.1016/j.blre.2006.01.003.

    Article  PubMed  Google Scholar 

  31. Lamy T, Loughran TP Jr. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003;40(3):185–95.

    Article  PubMed  Google Scholar 

  32. Arvanitidou IE, Nikitakis NG, Sklavounou A. Oral manifestations of T-cell large granular lymphocytic leukemia: a case report. J Oral Maxillofac Res. 2011;2(3):e4. https://doi.org/10.5037/jomr.2011.2304.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Go RS, Li CY, Tefferi A, Phyliky RL. Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood. 2001;98(2):483–5.

    Article  CAS  PubMed  Google Scholar 

  34. Cheng J, Talamo G, Malysz J, Ochmann M, Lamy T, Loughran TP Jr. Report of 6 cases of large granular lymphocytic leukemia and plasma cell dyscrasia. Clin Lymphoma Myeloma Leuk. 2014;14(5):e169–72. https://doi.org/10.1016/j.clml.2014.04.001.

    Article  PubMed  Google Scholar 

  35. Viny AD, Lichtin A, Pohlman B, Loughran T, Maciejewski J. Chronic B-cell dyscrasias are an important clinical feature of T-LGL leukemia. Leuk Lymphoma. 2008;49(5):932–8. https://doi.org/10.1080/10428190801932635.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang R, Shah MV, Loughran TP Jr. The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders. Hematol Oncol. 2010;28(3):105–17. https://doi.org/10.1002/hon.917.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chen X, Bai F, Sokol L, Zhou J, Ren A, Painter JS, et al. A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia. Blood. 2009;113(14):3226–34. https://doi.org/10.1182/blood-2008-07-168245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Grossi O, Horeau-Langlard D, Agard C, Haloun A, Lefebvre M, Neel A, et al. Low-dose methotrexate in PAH related to T-cell large granular lymphocyte leukaemia. Eur Respir J. 2012;39(2):493–4. https://doi.org/10.1183/09031936.00014811.

    Article  CAS  PubMed  Google Scholar 

  39. Goyal T, Thakral B, Wang SA, Bueso-Ramos CE, Shi M, Jevremovic D, et al. T-cell large granular lymphocytic leukemia and coexisting B-cell lymphomas: a study from the Bone Marrow Pathology Group. Am J Clin Pathol. 2018;149(2):164–71. https://doi.org/10.1093/ajcp/aqx146.

    Article  PubMed  Google Scholar 

  40. Poullot E, Bouscary D, Guyader D, Ghandour C, Roussel M, Fest T, et al. Large granular lymphocyte leukemia associated with hepatitis C virus infection and B cell lymphoma: improvement after antiviral therapy. Leuk Lymphoma. 2013;54(8):1797–9. https://doi.org/10.3109/10428194.2012.752486.

    Article  PubMed  Google Scholar 

  41. Lamy T, Loughran TP Jr. Pathogenesis of autoimmune diseases in large granular lymphocyte leukemia. Hematology. 1998;3(1):17–29. https://doi.org/10.1080/10245332.1998.11746376.

    Article  CAS  PubMed  Google Scholar 

  42. Clemente MJ, Wlodarski MW, Makishima H, Viny AD, Bretschneider I, Shaik M, et al. Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large granular lymphocyte leukemia. Blood. 2011;118(16):4384–93. https://doi.org/10.1182/blood-2011-02-338517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sandberg Y, Kallemeijn MJ, Dik WA, Tielemans D, Wolvers-Tettero IL, van Gastel-Mol EJ, et al. Lack of common TCRA and TCRB clonotypes in CD8(+)/TCRalphabeta(+) T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8(+) T-LGL. Blood Cancer J. 2014;4:e172. https://doi.org/10.1038/bcj.2013.70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen J, Petrus M, Bamford R, Shih JH, Morris JC, Janik JE, et al. Increased serum soluble IL-15Ralpha levels in T-cell large granular lymphocyte leukemia. Blood. 2012;119(1):137–43. https://doi.org/10.1182/blood-2011-04-346759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang J, Liu X, Nyland SB, Zhang R, Ryland LK, Broeg K, et al. Platelet-derived growth factor mediates survival of leukemic large granular lymphocytes via an autocrine regulatory pathway. Blood. 2010;115(1):51–60. https://doi.org/10.1182/blood-2009-06-223719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Teramo A, Gattazzo C, Passeri F, Lico A, Tasca G, Cabrelle A, et al. Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia. Blood. 2013;121(19):3843–54, S1. https://doi.org/10.1182/blood-2012-07-441378.

    Article  CAS  PubMed  Google Scholar 

  47. Kothapalli R, Nyland SB, Kusmartseva I, Bailey RD, McKeown TM, Loughran TP Jr. Constitutive production of proinflammatory cytokines RANTES, MIP-1beta and IL-18 characterizes LGL leukemia. Int J Oncol. 2005;26(2):529–35.

    CAS  PubMed  Google Scholar 

  48. Schade AE, Powers JJ, Wlodarski MW, Maciejewski JP. Phosphatidylinositol-3-phosphate kinase pathway activation protects leukemic large granular lymphocytes from undergoing homeostatic apoptosis. Blood. 2006;107(12):4834–40. https://doi.org/10.1182/blood-2005-08-3076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shah MV, Zhang R, Irby R, Kothapalli R, Liu X, Arrington T, et al. Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood. 2008;112(3):770–81. https://doi.org/10.1182/blood-2007-11-121871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Johansson P, Bergmann A, Rahmann S, Wohlers I, Scholtysik R, Przekopowitz M, et al. Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia. Int J Cancer. 2016;138(1):121–4. https://doi.org/10.1002/ijc.29697.

    Article  CAS  PubMed  Google Scholar 

  51. Lamy T, Liu JH, Landowski TH, Dalton WS, Loughran TP Jr. Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia. Blood. 1998;92(12):4771–7.

    CAS  PubMed  Google Scholar 

  52. Yang J, Epling-Burnette PK, Painter JS, Zou J, Bai F, Wei S, et al. Antigen activation and impaired Fas-induced death-inducing signaling complex formation in T-large-granular lymphocyte leukemia. Blood. 2008;111(3):1610–6. https://doi.org/10.1182/blood-2007-06-093823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu JH, Wei S, Lamy T, Li Y, Epling-Burnette PK, Djeu JY, et al. Blockade of Fas-dependent apoptosis by soluble Fas in LGL leukemia. Blood. 2002;100(4):1449–53.

    CAS  PubMed  Google Scholar 

  54. Liu JH, Wei S, Lamy T, Epling-Burnette PK, Starkebaum G, Djeu JY, et al. Chronic neutropenia mediated by Fas ligand. Blood. 2000;95(10):3219–22.

    CAS  PubMed  Google Scholar 

  55. Saitoh T, Karasawa M, Sakuraya M, Norio N, Junko T, Shirakawa K, 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(4):272–5.

    Article  CAS  PubMed  Google Scholar 

  56. Fasan A, Kern W, Grossmann V, Haferlach C, Haferlach T, Schnittger S. STAT3 mutations are highly specific for large granular lymphocytic leukemia. Leukemia. 2013;27(7):1598–600. https://doi.org/10.1038/leu.2012.350.

    Article  CAS  PubMed  Google Scholar 

  57. Sandherr M, Hentrich M, von Lilienfeld-Toal M, Massenkeil G, Neumann S, Penack O, et al. Antiviral prophylaxis in patients with solid tumours and haematological malignancies—update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Hematol. 2015;94(9):1441–50. https://doi.org/10.1007/s00277-015-2447-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017;96(11):1775–92. https://doi.org/10.1007/s00277-017-3098-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sood R, Stewart CC, Aplan PD, Murai H, Ward P, Barcos M, 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(9):3372–8.

    CAS  PubMed  Google Scholar 

  60. Fujishima N, Sawada K, Hirokawa M, Oshimi K, Sugimoto K, Matsuda A, et al. Long-term responses and outcomes following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia: a Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group. Haematologica. 2008;93(10):1555–9. https://doi.org/10.3324/haematol.12871.

    Article  CAS  PubMed  Google Scholar 

  61. Loughran TP Jr, Kidd PG, Starkebaum G. Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood. 1994;84(7):2164–70.

    PubMed  Google Scholar 

  62. Sanikommu SR, Clemente MJ, Chomczynski P, Afable MG 2nd, Jerez A, Thota S, et al. Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL). Leuk Lymphoma. 2018;59(2):416–22. https://doi.org/10.1080/10428194.2017.1339880.

    Article  PubMed  Google Scholar 

  63. Battiwalla M, Melenhorst J, Saunthararajah Y, Nakamura R, Molldrem J, Young NS, et al. HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders. Br J Haematol. 2003;123(3):449–53.

    Article  CAS  PubMed  Google Scholar 

  64. Loughran TP Jr, Zickl L, Olson TL, Wang V, Zhang D, Rajala HL, et al. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015;29(4):886–94. https://doi.org/10.1038/leu.2014.298.

    Article  CAS  PubMed  Google Scholar 

  65. Dubey L, Chatterjee S, Ghosh A. Hepatic and hematological adverse effects of long-term low-dose methotrexate therapy in rheumatoid arthritis: an observational study. Indian J Pharmacol. 2016;48(5):591–4. https://doi.org/10.4103/0253-7613.190761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Dumitriu B, Ito S, Feng X, Stephens N, Yunce M, Kajigaya S, et al. Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study. Lancet Haematol. 2016;3(1):e22–9. https://doi.org/10.1016/S2352-3026(15)00227-6.

    Article  PubMed  Google Scholar 

  67. Kadia TM, Ravandi F. Alemtuzumab in T-cell large granular lymphocyte leukaemia. Lancet Haematol. 2016;3(1):e4–5. https://doi.org/10.1016/S2352-3026(15)00281-1.

    Article  PubMed  Google Scholar 

  68. Fortune AF, Kelly K, Sargent J, O’Brien D, Quinn F, Chadwick N, et al. Large granular lymphocyte leukemia: natural history and response to treatment. Leuk Lymphoma. 2010;51(5):839–45. https://doi.org/10.3109/10428191003706947.

    Article  CAS  PubMed  Google Scholar 

  69. Osuji N, Matutes E, Tjonnfjord G, Grech H, Del Giudice I, Wotherspoon A, 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(3):570–8. https://doi.org/10.1002/cncr.22032.

    Article  PubMed  Google Scholar 

  70. Marchand T, Lamy T, Finel H, Arcese W, Choquet S, Finke J, et al. Hematopoietic stem cell transplantation for T-cell large granular lymphocyte leukemia: a retrospective study of the European Society for Blood and Marrow Transplantation. Leukemia. 2016;30(5):1201–4. https://doi.org/10.1038/leu.2015.256.

    Article  CAS  PubMed  Google Scholar 

  71. Genvresse I, Spath-Schwalbe E, Lukowsky A, Possinger K. Delayed response to granulocyte colony-stimulating factor (G-CSF) in a case of severe neutropenia associated with large granular lymphocyte (LGL) leukemia. Eur J Haematol. 1998;60(2):133–4.

    Article  CAS  PubMed  Google Scholar 

  72. Weide R, Heymanns J, Koppler H, Tiemann M, Huss B, Pfluger KH, et al. Successful treatment of neutropenia in T-LGL leukemia (T gamma-lymphocytosis) with granulocyte colony-stimulating factor. Ann Hematol. 1994;69(3):117–9.

    Article  CAS  PubMed  Google Scholar 

  73. Stanworth SJ, Bhavnani M, Chattopadhya C, Miller H, Swinson DR. Treatment of Felty’s syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF). QJM. 1998;91(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  74. Subbiah V, Viny AD, Rosenblatt S, Pohlman B, Lichtin A, Maciejewski JP. Outcomes of splenectomy in T-cell large granular lymphocyte leukemia with splenomegaly and cytopenia. Exp Hematol. 2008;36(9):1078–83. https://doi.org/10.1016/j.exphem.2008.04.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Waldmann TA, Conlon KC, Stewart DM, Worthy TA, Janik JE, Fleisher TA, et al. Phase 1 trial of IL-15 trans presentation blockade using humanized Mikbeta1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood. 2013;121(3):476–84. https://doi.org/10.1182/blood-2012-08-450585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Epling-Burnette PK, Sokol L, Chen X, Bai F, Zhou J, Blaskovich MA, et al. Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling. Blood. 2008;112(12):4694–8. https://doi.org/10.1182/blood-2008-02-136382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bilori B, Thota S, Clemente MJ, Patel B, Jerez A, Afable Ii M, et al. Tofacitinib as a novel salvage therapy for refractory T-cell large granular lymphocytic leukemia. Leukemia. 2015;29(12):2427–9. https://doi.org/10.1038/leu.2015.280.

    Article  CAS  PubMed  Google Scholar 

  78. Eichhorst B, Robak T, Montserrat E, Ghia P, Hillmen P, Hallek M, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v78–84. https://doi.org/10.1093/annonc/mdv303.

    Article  PubMed  Google Scholar 

  79. Faurschou M, Mellemkjaer L, Voss A, Keller KK, Hansen IT, Baslund B. Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis. Rheumatology (Oxford). 2015;54(8):1345–50. https://doi.org/10.1093/rheumatology/keu372.

    Article  CAS  Google Scholar 

  80. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27(4):605–11. https://doi.org/10.1200/JCO.2008.18.0182.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Hematology, University Hospital Essen, Essen, Germany

    Jan Dürig

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  1. Department I of Internal Medicine, University of Cologne, Cologne, Nordrhein-Westfalen, Germany

    Michael Hallek

  2. Department I of Internal Medicine, University of Cologne, Cologne, Nordrhein-Westfalen, Germany

    Barbara Eichhorst

  3. Division of Molecular Pathology, The Institute of Cancer Research, London, UK

    Daniel Catovsky

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Dürig, J. (2019). Large Granular Lymphocyte Leukemia. In: Hallek, M., Eichhorst, B., Catovsky, D. (eds) Chronic Lymphocytic Leukemia. Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-11392-6_12

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  • DOI: https://doi.org/10.1007/978-3-030-11392-6_12

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-11391-9

  • Online ISBN: 978-3-030-11392-6

  • eBook Packages: MedicineMedicine (R0)

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