Top

Published in:

01-04-2010 | Review Article

T-cell large granular lymphocyte leukemia: an Asian perspective

Authors: Yok-Lam Kwong, Wing-Yan Au, Anskar Y. H. Leung, Eric W. C. Tse

Published in: Annals of Hematology | Issue 4/2010

Abstract

To characterize T-cell large granular leukemia in Asia, 22 Chinese patients from a single institute were reported, together with an analysis of 88 Asian and 272 Western patients identified from the literature. In our cohort, anemia due to pure red cell aplasia (PRCA) occurred in 15/22 (68%) of cases, being the most common indication for treatment. Neutropenia was only found in 8/22 (36%) cases, and recurrent infections, the most important clinical problem in Western patients, were not observed. None of our cases presented with rheumatoid arthritis. These clinical features were consistently observed when compared with the 88 other Asian patients. Combined data from our cohort and other Asian cases showed that Asian patients, compared with Western patients, had more frequent anemia (66/110, 60% versus 113/240, 47%; p = 0.044), attributable to a much higher incidence of PRCA (52/110, 47% versus 6/143, 4%; p < 0.001). However, Western patients presented more frequently than Asian patients with neutropenia (146/235, 62% versus 33/110, 30%; p < 0.001) and splenomegaly (99/246, 40% versus 16/110, 15%; p < 0.001). Notably, Western patients were about eight to ten times more likely than Asian patients to have rheumatoid arthritis (73/272, 27% versus 4/106, 4%; p < 0.001) and recurrent infections (81/272, 30% versus 3/107, 3%; p < 0.001). These clinicopathologic differences have important implications on disease pathogenesis and treatment.

Available only for authorised users

Chan WC, Foucar K, Morice WG, Catovsky D (2008) T-cell large granular lymphocyte leukaemia. In: Swerdlow SH, Campo H, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency of Research On Cancer, Lyon, pp 272–273

Loughran TP Jr (1993) Clonal diseases of large granular lymphocytes. Blood 82:1–14PubMed

Sokol L, Loughran TP Jr (2006) Large granular lymphocyte leukemia. Oncologist 11:263–273CrossRefPubMed

Rose MG, Berliner N (2004) T-cell large granular lymphocyte leukemia and related disorders. Oncologist 9:247–258CrossRefPubMed

Oshimi K, Yamada O, Kaneko T, Nishinarita S, Iizuka Y, Urabe A, Inamori T, Asano S, Takahashi S, Hattori M, Naohara T, Ohira Y, Tigawa A, Masuda Y, Okuda Y, Furusawa S, Sakamoto S, Omine M, Mori M, Tatsumi E, Mizoguchi H (1993) Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders. Leukemia 7:782–788PubMed

Chan JK, Wong KF, Jaffe ES, Ralfkiaer E (2001) Aggressive NK-cell leukemia. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) Tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumours. IARC Press, Lyon, pp 198–200

Au WY, Lam CC, Lie AK, Pang A, Kwong YL (2003) T-cell large granular lymphocyte leukemia of donor origin after allogeneic bone marrow transplantation. Am J Clin Pathol 120:626–630CrossRefPubMed

Ma SY, Au WY, Chim CS, Lie AK, Lam CC, Tse E, Leung AY, Liang R, Kwong YL (2004) Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients. Br J Haematol 124:754–761CrossRefPubMed

Tse E, Chan JC, Pang A, Au WY, Leung AY, Lam CC, Kwong YL (2007) Fludarabine, mitoxantrone and dexamethasone as first-line treatment for T-cell large granular lymphocyte leukemia. Leukemia 21:2225–2226CrossRefPubMed

10.

Hwang YY, Leung AY, Ng IO, Chan GS, Chan KW, Tse E, Kwong YL (2009) Protein-losing enteropathy due to T-cell large granular lymphocyte leukemia. J Clin Oncol 27:2097–2098CrossRefPubMed

11.

Oshimi K, Hoshino S, Takahashi M, Akahoshi M, Saito H, Kobayashi Y, Hirai H, Takaku F, Yahagi N, Oshimi Y et al (1988) Ti (WT31)-negative, CD3-positive, large granular lymphocyte leukemia with nonspecific cytotoxicity. Blood 71:923–931PubMed

12.

Ohno Y, Amakawa R, Fukuhara S, Huang CR, Kamesaki H, Amano H, Imanaka T, Takahashi Y, Arita Y, Uchiyama T, Kita K, Miwa H (1989) Acute transformation of chronic large granular lymphocyte leukemia associated with additional chromosome abnormality. Cancer 64:63–67CrossRefPubMed

13.

Morikawa K, Oseko F, Hara J, Kobayashi S, Nakano A, Morikawa S (1990) Functional analysis of clonally expanded CD8, TCR gamma delta T cells in a patient with chronic T-gamma lymphoproliferative disease. Leuk Res 14:581–592CrossRefPubMed

14.

Kwong YL, Wong KF, Chan LC, Liang RH, Chan JK, Lin CK, Chan TK (1995) Large granular lymphocyte leukemia. A study of nine cases in a Chinese population. Am J Clin Pathol 103:76–81PubMed

15.

Masuda M, Arai Y, Nishina H, Fuchinoue S, Mizoguchi H (1998) Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient. Am J Hematol 57:72–76CrossRefPubMed

16.

Akashi K, Shibuya T, Nakamura M, Oogami A, Harada M, Niho Y (1998) Large granular lymphocytic leukaemia with a mixed T-cell/B-cell phenotype. Br J Haematol 100:291–294CrossRefPubMed

17.

Takeuchi M, Tamaoki A, Soda R, Takahashi K (1999) Spontaneous remission of large granular lymphocyte T cell leukemia. Leukemia 13:313–314CrossRefPubMed

18.

Saitoh T, Karasawa M, Sakuraya M, Norio N, Junko T, Shirakawa K, Matsushima T, Tsukamoto N, Nojima Y, Murakami H (2000) 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 65:272–275CrossRefPubMed

19.

Kondo H, Mori A, Watanabe J, Takada J, Takahashi Y, Iwasaki H (2001) Pure red cell aplasia associated with parvovirus B19 infection in T-large granular lymphocyte leukemia. Leuk Lymphoma 42:1439–1443CrossRefPubMed

20.

Matsuo Y, Drexler HG, Takeuchi M, Tanaka M, Orita K (2002) Establishment of the T-cell large granular lymphocyte leukemia cell line MOTN-1 carrying natural killer-cell antigens. Leuk Res 26:873–879CrossRefPubMed

21.

Lee PS, Hwang WS (2002) Pathologic quiz case: chronic anemia with red cell aplasia and lymphocytosis in a middle-aged man. T-cell large granular lymphocyte leukemia. Arch Pathol Lab Med 126:1549–1550PubMed

22.

Karasawa M, Mitsui T, Isoda A, Tsumita Y, Irisawa H, Yokohama A, Handa H, Matsushima T, Tsukamoto N, Murakami H, Nojima Y (2003) TCR Vbeta repertoire analysis in CD56+ CD16(dim/-) T-cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes. Br J Haematol 123:613–620CrossRefPubMed

23.

Wong KF, Yip SF, So CC, Lau GT, Yeung YM (2003) Cytomegalovirus infection associated with clonal proliferation of T-cell large granular lymphocytes: causal or casual? Cancer Genet Cytogenet 142:77–79CrossRefPubMed

24.

Kato N, Tamura A, Yamanaka Y, Tanimura S, Aikawa K, Morikawa R (2004) CD3+ TCRgammadelta + CD4+ CD8- T-cell large granular lymphocyte leukaemia showing skin infiltrations. Br J Dermatol 150:382–384CrossRefPubMed

25.

Narumi H, Kojima K, Matsuo Y, Shikata H, Sekiya K, Niiya T, Bando S, Niiya H, Azuma T, Yakushijin Y, Sakai I, Yasukawa M, Fujita S (2004) T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 33:99–101CrossRefPubMed

26.

Shichishima T, Kawaguchi M, Ono N, Oshimi K, Nakamura N, Maruyama Y (2004) Gammadelta T-cell large granular lymphocyte (LGL) leukemia with spontaneous remission. Am J Hematol 75:168–172CrossRefPubMed

27.

Tanaka Y, Matsui K, Yamashita K, Matsuda K, Shinohara K, Matsutani A (2006) T-gamma delta large granular lymphocyte leukemia preceded by pure red cell aplasia and complicated with hemophagocytic syndrome caused by Epstein-Barr virus infection. Intern Med 45:631–635CrossRefPubMed

28.

Yamada O, Mizoguchi H, Oshimi K (1997) Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte-proliferative disorders. Br J Haematol 97:392–399CrossRefPubMed

29.

Kawahara S, Sasaki M, Isobe Y, Ando J, Noguchi M, Koike M, Hirano T, Oshimi K, Sugimoto K (2009) Clinical analysis of 52 patients with granular lymphocyte proliferative disorder (GLPD) showed frequent anemia in indolent T-cell GLPD in Japan. Eur J Haematol 82:308–314CrossRefPubMed

30.

Dhodapkar MV, Li CY, Lust JA, Tefferi A, Phyliky RL (1994) Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 84:1620–1627PubMed

31.

Osuji N, Matutes E, Tjonnfjord G, Grech H, Del Giudice I, Wotherspoon A, Swansbury JG, Catovsky D (2006) T-cell large granular lymphocyte leukemia: A report on the treatment of 29 patients and a review of the literature. Cancer 107:570–578CrossRefPubMed

32.

Aribi A, Huh Y, Keating M, O'brien S, Ferrajoli A, Faderl S, Wierda W, Kantarjian H, Ravandi F (2007) T-cell large granular lymphocytic (T-LGL) leukemia: experience in a single institution over 8 years. Leuk Res 31:939–945CrossRefPubMed

33.

Bourgault-Rouxel AS, Loughran TP Jr, Zambello R, Epling-Burnette PK, Semenzato G, Donadieu J, Amiot L, Fest T, Lamy T (2008) Clinical spectrum of gammadelta + T cell LGL leukemia: analysis of 20 cases. Leuk Res 32:45–48CrossRefPubMed

34.

Lamy T, Loughran TP Jr (2003) Clinical features of large granular lymphocyte leukemia. Semin Hematol 40:185–195CrossRefPubMed

35.

Kwong YL, Wong KF, Liang RH, Chu YC, Chan LC, Chan TK (1996) Pure red cell aplasia: clinical features and treatment results in 16 cases. Ann Hematol 72:137–140CrossRefPubMed

36.

Lacy MQ, Kurtin PJ, Tefferi A (1996) Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities. Blood 87:3000–3006PubMed

37.

Kwong YL, Wong KF (1998) Association of pure red cell aplasia with T large granular lymphocyte leukaemia. J Clin Pathol 51:672–675CrossRefPubMed

38.

Go RS, Li CY, Tefferi A, Phyliky RL (2001) Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood 98:483–485CrossRefPubMed

39.

Burks EJ, Loughran TP Jr (2006) Pathogenesis of neutropenia in large granular lymphocyte leukemia and Felty syndrome. Blood Rev 20:245–266CrossRefPubMed

40.

Epling-Burnette PK, Loughran TP Jr (2003) Survival signals in leukemic large granular lymphocytes. Semin Hematol 40:213–220CrossRefPubMed

41.

Zambello R, Trentin L, Facco M, Cerutti A, Sancetta R, Milani A, Raimondi R, Tassinari C, Agostini C, Semenzato G (1995) Analysis of the T cell receptor in the lymphoproliferative disease of granular lymphocytes: superantigen activation of clonal CD3+ granular lymphocytes. Cancer Res 55:6140–6145PubMed

42.

Wlodarski MW, O'Keefe C, Howe EC, Risitano AM, Rodriguez A, Warshawsky I, Loughran TP Jr, Maciejewski JP (2005) Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell-receptor restriction in large granular lymphocyte leukemia. Blood 106:2769–2780CrossRefPubMed

43.

O'Malley DP (2007) T-cell large granular leukemia and related proliferations. Am J Clin Pathol 127:850–859CrossRefPubMed

44.

Mori KL, Furukawa H, Hayashi K, Sugimoto KJ, Oshimi K (2003) Pure red cell aplasia associated with expansion of CD3+ CD8+ granular lymphocytes expressing cytotoxicity against HLA-E + cells. Br J Haematol 123:147–153CrossRefPubMed

45.

Sood R, Stewart CC, Aplan PD, Murai H, Ward P, Barcos M, Baer MR (1998) Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term response to cyclosporine therapy despite persistence of abnormal cells. Blood 91:3372–3378PubMed

46.

Sternberg A, Eagleton H, Pillai N, Leyden K, Turner S, Pearson D, Littlewood D, Hatton C (2003) Neutropenia and anaemia associated with T-cell large granular lymphocyte leukaemia responds to fludarabine with minimal toxicity. Br J Haematol 120:699–701CrossRefPubMed

47.

Au WY, Lam CC, Chim CS, Pang AW, Kwong YL (2005) Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia. Leuk Res 29:1213–1215CrossRefPubMed

48.

Schützinger C, Gaiger A, Thalhammer R, Vesely M, Fritsche-Polanz R, Schwarzinger I, Ohler L, Simonitsch-Klupp I, Reinhard F, Jäger U (2005) Remission of pure red cell aplasia in T-cell receptor gammadelta-large granular lymphocyte leukemia after therapy with low-dose alemtuzumab. Leukemia 19:2005–2008CrossRefPubMed

Title: T-cell large granular lymphocyte leukemia: an Asian perspective
Authors: Yok-Lam Kwong
Wing-Yan Au
Anskar Y. H. Leung
Eric W. C. Tse
Publication date: 01-04-2010
Publisher: Springer-Verlag
Published in: Annals of Hematology / Issue 4/2010
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-009-0895-3

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

T-cell large granular lymphocyte leukemia: an Asian perspective

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2010

Reversal of multidrug resistance by curcumin through FA/BRCA pathway in multiple myeloma cell line MOLP-2/R

Hemophagocytosis associated with leukemia: a striking association with juvenile myelomonocytic leukemia

Reduction of 5-azacitidine induced skin reactions in MDS patients with evening primrose oil

Decreased hemolysis following administration of antioxidant—fermented papaya preparation (FPP) to a patient with PNH

Relevance of target cell-induced apoptosis as mechanism of resistance against natural killer cells

Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page