T-cell large granular lymphocytic (T-LGL) leukemia is an indolent neoplasm characterized by a persistent (>6 months) increase in peripheral blood LGLs, usually between 2 and 20 × 109/L.1 Patients often present with neutropenia, splenomegaly, and autoimmune disorders. The LGLs are typically cytotoxic T cells expressing CD3, CD8, and T-cell receptor (TCR) αβ, with monoclonal TCR gene rearrangements. The pathogenesis of T-LGL leukemia is not well defined. However, chronic antigenic stimulation has been suggested as one underlying mechanism because of the frequent association between T-LGL leukemia and autoimmune disorders.2
T-LGL proliferation has been observed after allogeneic and autologous hematopoietic stem cell transplantation (SCT).3–6 The expanded T-LGLs are usually polyclonal or oligoclonal. Rare cases of T-LGL leukemia have also been reported after hematopoietic SCT,7–12 with a frequency of 0.5%.12 Whereas most patients with T-LGL leukemia occurring in the post-SCT setting had remained asymptomatic with stable LGL counts and did not require specific treatment,9,12 rare patients have been reported with an aggressive clinical course with progressive pancytopenia and death in a short interval.8
We report a case of a young patient with a history of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) who developed T-LGL leukemia of donor origin after allogeneic SCT, with a comprehensive literature review. A diagnostic algorithm to distinguish T-LGL leukemia and T-LGL proliferation and other lymphoproliferative disorders after SCT is proposed.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
See JNCCN.org for supplemental online content.
Chan WC, Foucar K, Morice WG et al.. T-cell large granular lymphocytic leukemia. In: Swerdlow SH, Campo E, Harris NL et al., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2008:272–273.
Zambello R, Semenzato G. Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches. Haematologica 2009;94:1341–1345.
Dolstra H, Preijers F, Van de Wiel-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.
Mohty 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.
Nann-Rutti S, Tzankov A, Cantoni N et al.. Large granular lymphocyte expansion after allogeneic hematopoietic stem cell transplant is associated with a cytomegalovirus reactivation and shows an indolent outcome. Biol Blood Marrow Transplant 2012;18:1765–1770.
Kim D, Al-Dawsari G, Chang H et al.. Large granular lymphocytosis and its impact on long-term clinical outcomes following allo-SCT. Bone Marrow Transplant 2013;48:1104–1111.
Wong KF, Yip SF, So CC et al.. Cytomegalovirus infection associated with clonal proliferation of T-cell large granular lymphocytes: causal or casual? Cancer Genet Cytogenet 2003;142:77–79.
Au WY, Lam CC, Lie AK et al.. T-cell large granular lymphocyte leukemia of donor origin after allogeneic bone marrow transplantation. Am J Clin Pathol 2003;120:626–630.
Narumi H, Kojima K, Matsuo Y et al.. T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2004;33:99–101.
Chang H, Kamel-Reid S, Hussain N et al.. T-cell large granular lymphocytic leukemia of donor origin occurring after allogeneic bone marrow transplantation for B-cell lymphoproliferative disorders. Am J Clin Pathol 2005;123:196–199.
Kusumoto S, Mori S, Nosaka K et al.. T-cell large granular lymphocyte leukemia of donor origin after cord blood transplantation. Clin Lymphoma Myeloma 2007;7:475–479.
Gill H, Ip AH, Leung R et al.. Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis. Bone Marrow Transplant 2012;47:952–956.
Bareau B, Rey J, Hamidou M et al.. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica 2010;95:1534–1541.
Koskela HL, Eldfors S, Ellonen P et al.. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 2012;366:1905–1913.
Fasan A, Kern W, Grossmann V et al.. STAT3 mutations are highly specific for large granular lymphocytic leukemia. Leukemia 2013;27:1598–1600.
Liang CS, Quesada AE, Goswami M et al.. Phosphorylated STAT3 expression in hematopoietic stem cell transplant-associated large granular lymphocytic leukemia. Bone Marrow Transplant 2016;51:741–743.
Bilori B, Thota S, Clemente MJ et al.. Tofacitinib as a novel salvage therapy for refractory T-cell large granular lymphocytic leukemia. Leukemia 2015;29:2427–2429.