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Erschienen in: International Journal of Hematology 3/2019

27.06.2019 | Original Article

T-cell large granular lymphocyte leukemia in solid organ transplant recipients: case series and review of the literature

verfasst von: Gaetano Alfano, Francesco Fontana, Elisabetta Colaci, Giacomo Mori, Caterina Cerami, Andrea Messerotti, Leonardo Potenza, Mario Luppi, Gianni Cappelli

Erschienen in: International Journal of Hematology | Ausgabe 3/2019

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Abstract

T-cell large granular lymphocyte (T-LGL) leukemia is a rare clonal proliferation of cytotoxic lymphocytes rarely described in solid organ transplant (SOT). We reviewed records from 656 kidney transplant recipients in follow-up at our Center from January 1998 to July 2017. In addition, we researched, through PubMed, further reports of T-LGL leukemia in SOT from March 1981 to December 2017. We identified six cases of T-LGL leukemia in our cohort of patients and 10 in the literature. This lymphoproliferative disorder was detected in one combined liver–kidney, one liver and 14–kidney transplant recipients. Median age at presentation was 46.5 years (IQR 39.2–56.9). The disease developed after a median age of 10 years (IQR 4.9–12) from transplantation. Anemia was the most common presentation (62.5%) followed by lymphocytosis (43.7%) and thrombocytopenia (31.2%). Splenomegaly was reported in 43.7% of the patients. Eight patients (50%) who experienced severe symptoms were treated with non-specific immunosuppressive agents. Six of them (75%) had a good outcome, whereas two (25%) remained red blood cell transfusion dependent. No cases progressed to aggressive T-LGL leukemia or died of cancer at the end of follow-up. These results suggest that T-LGL leukemia is a rare but potentially disruptive hematological disorder in the post-transplant period.
Literatur
1.
Zurück zum Zitat Swerdllow SH, Harris NL. WHO classification of tumours of haematopoietic and lymphoid tissues. France: IARC Press; 2008. Swerdllow SH, Harris NL. WHO classification of tumours of haematopoietic and lymphoid tissues. France: IARC Press; 2008.
2.
Zurück zum Zitat Timonen T, Ortaldo JR, Herberman RB. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981;153(3):569–82.CrossRef Timonen T, Ortaldo JR, Herberman RB. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981;153(3):569–82.CrossRef
3.
Zurück zum Zitat Sokol L, Loughran TP. Large granular lymphocyte leukemia. Oncologist. 2006;11(3):263–73.CrossRef Sokol L, Loughran TP. Large granular lymphocyte leukemia. Oncologist. 2006;11(3):263–73.CrossRef
4.
Zurück zum Zitat Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood. 2017;129(9):1082–94.CrossRef Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood. 2017;129(9):1082–94.CrossRef
5.
Zurück zum Zitat Lima M, et al. TCRαβ+/CD4+ large granular lymphocytosis. Am J Pathol. 2003;163(2):763–71.CrossRef Lima M, et al. TCRαβ+/CD4+ large granular lymphocytosis. Am J Pathol. 2003;163(2):763–71.CrossRef
6.
Zurück zum Zitat Sandberg Y, et al. TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T cells. Leukemia. 2006;20(3):505–13.CrossRef Sandberg Y, et al. TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T cells. Leukemia. 2006;20(3):505–13.CrossRef
7.
Zurück zum Zitat Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood. 1997;89(1):256–60.PubMed Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood. 1997;89(1):256–60.PubMed
8.
Zurück zum Zitat Bareau B, 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.CrossRef Bareau B, 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.CrossRef
9.
Zurück zum Zitat Mohan SR, Maciejewski JP. Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia. Curr Opin Hematol. 2009;16(1):27–34.CrossRef Mohan SR, Maciejewski JP. Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia. Curr Opin Hematol. 2009;16(1):27–34.CrossRef
10.
Zurück zum Zitat Hodges E, Krishna MT, Pickard C, Smith JL. Diagnostic role of tests for T cell receptor (TCR) genes. J Clin Pathol. 2003;56(1):1–11.CrossRef Hodges E, Krishna MT, Pickard C, Smith JL. Diagnostic role of tests for T cell receptor (TCR) genes. J Clin Pathol. 2003;56(1):1–11.CrossRef
11.
Zurück zum Zitat Berliner N, et al. T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia. Blood. 1986;67(4):914–8.PubMed Berliner N, et al. T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia. Blood. 1986;67(4):914–8.PubMed
12.
Zurück zum Zitat Lamy T, Liu JH, Landowski TH, Dalton WS, Loughran TP. Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia. Blood. 1998;92(12):4771–7.PubMed Lamy T, Liu JH, Landowski TH, Dalton WS, Loughran TP. Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia. Blood. 1998;92(12):4771–7.PubMed
13.
Zurück zum Zitat Epling-Burnette PK, et al. ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL). Oncogene. 2004;23(57):9220–9.CrossRef Epling-Burnette PK, et al. ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL). Oncogene. 2004;23(57):9220–9.CrossRef
14.
Zurück zum Zitat Teramo A, et al. STAT3 mutation impacts biological and clinical features of T-LGL leukemia. Oncotarget. 2017;8(37):61876–89.CrossRef Teramo A, et al. STAT3 mutation impacts biological and clinical features of T-LGL leukemia. Oncotarget. 2017;8(37):61876–89.CrossRef
15.
Zurück zum Zitat Loughran P, Thomas P, et al. Epitope mapping of HTLV envelope seroreactivity in LGL leukaemia. Br. J. Haematol. 1998;101(2):318–24.CrossRef Loughran P, Thomas P, et al. Epitope mapping of HTLV envelope seroreactivity in LGL leukaemia. Br. J. Haematol. 1998;101(2):318–24.CrossRef
16.
Zurück zum Zitat Sokol L, Agrawal D, Loughran TP. Characterization of HTLV envelope seroreactivity in large granular lymphocyte leukemia. Leuk Res. 2005;29(4):381–7.CrossRef Sokol L, Agrawal D, Loughran TP. Characterization of HTLV envelope seroreactivity in large granular lymphocyte leukemia. Leuk Res. 2005;29(4):381–7.CrossRef
17.
Zurück zum Zitat Wlodarski MW, et al. Pathologic clonal cytotoxic T cell responses: nonrandom nature of the T cell–receptor restriction in large granular lymphocyte leukemia. Blood. 2005;106(8):2769–80.CrossRef Wlodarski MW, et al. Pathologic clonal cytotoxic T cell responses: nonrandom nature of the T cell–receptor restriction in large granular lymphocyte leukemia. Blood. 2005;106(8):2769–80.CrossRef
18.
Zurück zum Zitat Lamy T, Loughran TP. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003;40(3):185–95.CrossRef Lamy T, Loughran TP. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003;40(3):185–95.CrossRef
19.
Zurück zum Zitat Bowman SJ, et al. The large granular lymphocyte syndrome with rheumatoid arthritis. Immunogenetic evidence for a broader definition of Felty’s syndrome. Arthritis Rheum. 1994;37(9):1326–30.CrossRef Bowman SJ, et al. The large granular lymphocyte syndrome with rheumatoid arthritis. Immunogenetic evidence for a broader definition of Felty’s syndrome. Arthritis Rheum. 1994;37(9):1326–30.CrossRef
20.
Zurück zum Zitat Loughran TP. Clonal diseases of large granular lymphocytes. Blood. 1993;82(1):1–14.PubMed Loughran TP. Clonal diseases of large granular lymphocytes. Blood. 1993;82(1):1–14.PubMed
21.
Zurück zum Zitat Zhang R, Shah MV, Loughran TP. The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders. Hematol Oncol. 2010;28(3):105–17.PubMedPubMedCentral Zhang R, Shah MV, Loughran TP. The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders. Hematol Oncol. 2010;28(3):105–17.PubMedPubMedCentral
22.
Zurück zum Zitat Gentile TC, et al. CD3+ , CD56+ aggressive variant of large granular lymphocyte leukemia [see comments]. Blood. 1994;84(7):2315–21.PubMed Gentile TC, et al. CD3+ , CD56+ aggressive variant of large granular lymphocyte leukemia [see comments]. Blood. 1994;84(7):2315–21.PubMed
23.
Zurück zum Zitat Alekshun TJ, Tao J, Sokol L. Aggressive T cell large granular lymphocyte leukemia: a case report and review of the literature. Am J Hematol. 2007;82(6):481–5.CrossRef Alekshun TJ, Tao J, Sokol L. Aggressive T cell large granular lymphocyte leukemia: a case report and review of the literature. Am J Hematol. 2007;82(6):481–5.CrossRef
24.
Zurück zum Zitat Steinway SN, LeBlanc F, Loughran TP. The pathogenesis and treatment of large granular lymphocyte leukemia. Blood Rev. 2014;28(3):87–94.CrossRef Steinway SN, LeBlanc F, Loughran TP. The pathogenesis and treatment of large granular lymphocyte leukemia. Blood Rev. 2014;28(3):87–94.CrossRef
25.
Zurück zum Zitat Feher O, Barilla D, Locker J, Oliveri D, Melhem M, Winkelstein A. T cell large granular lymphocytic leukemia following orthotopic liver transplantation. Am J Hematol. 1995;49(3):216–20.CrossRef Feher O, Barilla D, Locker J, Oliveri D, Melhem M, Winkelstein A. T cell large granular lymphocytic leukemia following orthotopic liver transplantation. Am J Hematol. 1995;49(3):216–20.CrossRef
26.
Zurück zum Zitat Masuda M, Arai Y, Nishina H, Fuchinoue S, Mizoguchi H. Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient. Am J Hematol. 1998;57(1):72–6.CrossRef Masuda M, Arai Y, Nishina H, Fuchinoue S, Mizoguchi H. Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient. Am J Hematol. 1998;57(1):72–6.CrossRef
27.
Zurück zum Zitat Stamatopoulos K, et al. Large granular lymphocyte leukemia after renal transplantation: an immunologic, immunohistochemical, and genotypic study. Transplantation. 2007;83(1):102–3.CrossRef Stamatopoulos K, et al. Large granular lymphocyte leukemia after renal transplantation: an immunologic, immunohistochemical, and genotypic study. Transplantation. 2007;83(1):102–3.CrossRef
28.
Zurück zum Zitat Gentile TC, et al. Large granular lymphocyte leukaemia occurring after renal transplantation. Br J Haematol. 1998;101(3):507–12.CrossRef Gentile TC, et al. Large granular lymphocyte leukaemia occurring after renal transplantation. Br J Haematol. 1998;101(3):507–12.CrossRef
29.
Zurück zum Zitat Sabnani I, Zucker MJ, Tsang P, Palekar S. Clonal T-large granular lymphocyte proliferation in solid organ transplant recipients. Transplant. Proc. 2006;38(10):3437–40.CrossRef Sabnani I, Zucker MJ, Tsang P, Palekar S. Clonal T-large granular lymphocyte proliferation in solid organ transplant recipients. Transplant. Proc. 2006;38(10):3437–40.CrossRef
30.
Zurück zum Zitat Kataria A, Cohen E, Saad E, Atallah E, Bresnahan B. Large granular lymphocytic leukemia presenting late after solid organ transplantation: a case series of four patients and review of the literature. Transplant. Proc. 2014;46(10):3278–81.CrossRef Kataria A, Cohen E, Saad E, Atallah E, Bresnahan B. Large granular lymphocytic leukemia presenting late after solid organ transplantation: a case series of four patients and review of the literature. Transplant. Proc. 2014;46(10):3278–81.CrossRef
31.
Zurück zum Zitat Schiff J, Cole E, Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin. J. Am. Soc. Nephrol. CJASN. 2007;2(2):374–84.CrossRef Schiff J, Cole E, Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin. J. Am. Soc. Nephrol. CJASN. 2007;2(2):374–84.CrossRef
32.
Zurück zum Zitat Cattaneo D, et al. Therapeutic drug monitoring of sirolimus: effect of concomitant immunosuppressive therapy and optimization of drug dosing. Am J Transplant. 2004;4(8):1345–51.CrossRef Cattaneo D, et al. Therapeutic drug monitoring of sirolimus: effect of concomitant immunosuppressive therapy and optimization of drug dosing. Am J Transplant. 2004;4(8):1345–51.CrossRef
33.
Zurück zum Zitat Scotet E, et al. Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes. Eur J Immunol. 1999;29(3):973–85.CrossRef Scotet E, et al. Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes. Eur J Immunol. 1999;29(3):973–85.CrossRef
34.
Zurück zum Zitat Rose MG, Berliner N. T cell large granular lymphocyte leukemia and related disorders. Oncologist. 2004;9(3):247–58.CrossRef Rose MG, Berliner N. T cell large granular lymphocyte leukemia and related disorders. Oncologist. 2004;9(3):247–58.CrossRef
35.
Zurück zum Zitat Yabe M, et al. Clinicopathologic, immunophenotypic, cytogenetic, and molecular features of γδ T cell large granular lymphocytic leukemia: an analysis of 14 patients suggests biologic differences with αβ T cell large granular lymphocytic leukemia. Am J Clin Pathol. 2015;144(4):607–19 (corrected).CrossRef Yabe M, et al. Clinicopathologic, immunophenotypic, cytogenetic, and molecular features of γδ T cell large granular lymphocytic leukemia: an analysis of 14 patients suggests biologic differences with αβ T cell large granular lymphocytic leukemia. Am J Clin Pathol. 2015;144(4):607–19 (corrected).CrossRef
36.
Zurück zum Zitat Fujishima N, 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.CrossRef Fujishima N, 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.CrossRef
37.
Zurück zum Zitat Bible KC, Tefferi A. Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis. Br J Haematol. 1996;93(2):406–8.CrossRef Bible KC, Tefferi A. Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis. Br J Haematol. 1996;93(2):406–8.CrossRef
38.
Zurück zum Zitat Shah MV, Hook CC, Call TG, Go RS. A population-based study of large granular lymphocyte leukemia. Blood Cancer J. 2016;6(8):e455.CrossRef Shah MV, Hook CC, Call TG, Go RS. A population-based study of large granular lymphocyte leukemia. Blood Cancer J. 2016;6(8):e455.CrossRef
39.
Zurück zum Zitat Yamamoto JF, Goodman MT. Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997–2002. Cancer Causes Control. 2008;19(4):379–90.CrossRef Yamamoto JF, Goodman MT. Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997–2002. Cancer Causes Control. 2008;19(4):379–90.CrossRef
40.
Zurück zum Zitat 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.CrossRef 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.CrossRef
41.
Zurück zum Zitat Dearden C. Large granular lymphocytic leukaemia pathogenesis and management. Br J Haematol. 2011;152(3):273–83.CrossRef Dearden C. Large granular lymphocytic leukaemia pathogenesis and management. Br J Haematol. 2011;152(3):273–83.CrossRef
42.
Zurück zum Zitat Qiu Z-Y, Xu W, Li J-Y. Large granular lymphocytosis during dasatinib therapy. Cancer Biol Ther. 2014;15(3):247–55.CrossRef Qiu Z-Y, Xu W, Li J-Y. Large granular lymphocytosis during dasatinib therapy. Cancer Biol Ther. 2014;15(3):247–55.CrossRef
43.
Zurück zum Zitat Sosin MD, Handa SI. Spontaneous remission of large granular lymphocytic leukaemia. Int J Clin Pract. 2003;57(6):551–2.PubMed Sosin MD, Handa SI. Spontaneous remission of large granular lymphocytic leukaemia. Int J Clin Pract. 2003;57(6):551–2.PubMed
44.
Zurück zum Zitat Scornik JC, Meier-Kriesche H-U. Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention. Am. J. Transplant. 2011;11(9):1785–91.CrossRef Scornik JC, Meier-Kriesche H-U. Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention. Am. J. Transplant. 2011;11(9):1785–91.CrossRef
45.
Zurück zum Zitat Zafrani L, et al. Incidence, risk factors and clinical consequences of neutropenia following kidney transplantation: a retrospective study. Am. J. Transplant. 2009;9(8):1816–25.CrossRef Zafrani L, et al. Incidence, risk factors and clinical consequences of neutropenia following kidney transplantation: a retrospective study. Am. J. Transplant. 2009;9(8):1816–25.CrossRef
46.
Zurück zum Zitat Brown AE. Neutropenia, fever, and infection. Am J Med. 1984;76(3):421–8.CrossRef Brown AE. Neutropenia, fever, and infection. Am J Med. 1984;76(3):421–8.CrossRef
47.
Zurück zum Zitat Swerdlow SH. T cell and NK-cell posttransplantation lymphoproliferative disorders. Am J Clin Pathol. 2007;127(6):887–95.CrossRef Swerdlow SH. T cell and NK-cell posttransplantation lymphoproliferative disorders. Am J Clin Pathol. 2007;127(6):887–95.CrossRef
48.
Zurück zum Zitat Herreman A, et al. Clinicopathological characteristics of posttransplant lymphoproliferative disorders of T cell origin: single-center series of nine cases and meta-analysis of 147 reported cases. Leuk Lymphoma. 2013;54(10):2190–9.CrossRef Herreman A, et al. Clinicopathological characteristics of posttransplant lymphoproliferative disorders of T cell origin: single-center series of nine cases and meta-analysis of 147 reported cases. Leuk Lymphoma. 2013;54(10):2190–9.CrossRef
49.
Zurück zum Zitat Margolskee E, et al. Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders. Oncotarget. 2016;7(25):37636–48.CrossRef Margolskee E, et al. Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders. Oncotarget. 2016;7(25):37636–48.CrossRef
Metadaten
Titel
T-cell large granular lymphocyte leukemia in solid organ transplant recipients: case series and review of the literature
verfasst von
Gaetano Alfano
Francesco Fontana
Elisabetta Colaci
Giacomo Mori
Caterina Cerami
Andrea Messerotti
Leonardo Potenza
Mario Luppi
Gianni Cappelli
Publikationsdatum
27.06.2019
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 3/2019
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-019-02682-2

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