Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ DEFINITION ++ T-cell large-granular lymphocytic (T-LGL) leukemia results from the clonal expansion of large granular lymphocytes (LGL) with a T-cell (CD3+) phenotype and a clonal T-cell receptor gene rearrangement(s). Natural killer (NK)-LGL leukemia is a clonal expansion of LGL with a NK cell (CD3-) phenotype. It lacks convenient markers to determine clonality such as antigen receptor rearrangements. +++ T-LGL LEUKEMIA +++ Etiology and Pathogenesis ++ Suggestive evidence of a role for human T lymphotropic virus (HTLV) retroviral infection in some patients. Most patients are not infected with either HTLV-I or HTLV-II. Cytomegalovirus implicated in rare cases of CD4+ T-LGL. Epstein-Barr virus implicated in some cases of NK-LGL. Leukemic cells have features of antigen-activated cytotoxic T lymphocytes (CTL), suggesting role for antigen in initial LGL expansion. Constitutive overexpression of the Fas ligand (CD178), which also is found at high levels in patients' sera, may be a factor in many disease manifestations (e.g., neutropenia, rheumatoid arthritis). +++ Clinical Features ++ About half of patients have palpable splenomegaly. About one-third of patients have recurrent bacterial infections and/or "B symptoms" (e.g., low-grade fevers, night sweats, and/or weight loss) (aggressive variant) (see Table 58–1). About one-quarter of patients have rheumatoid arthritis, often with features of "Felty syndrome." Less than 10 percent of patients have lymphadenopathy. ++Table Graphic Jump LocationTABLE 58–1COMPARATIVE FEATURES OF LARGE GRANULAR LYMPHOCYTIC LEUKEMIAView Table||Download (.pdf) TABLE 58–1 COMPARATIVE FEATURES OF LARGE GRANULAR LYMPHOCYTIC LEUKEMIA Variable T-cell LGL Leukemia (Indolent type) T-cell LGL leukemia (Aggressive type) NK-LGL leukemia (Aggressive type) Chronic NK Lymphocytosis (Indolent type) Median age (years) 60 40 40 60 Male:female ratio 1 2 1 7 Phenotype CD3+CD16+CD57+Clonal TCRαβ rearrangement CD3+CD16+CD56+Clonal TCRαβ rearrangement CD3–CD16+CD56+ CD3–CD16+ CD56+ Clinical features One-third asymptomatic Two-thirds symptomatic Cytopenias, splenomegaly, rheumatoid arthritis (~25% of patients). Symptomatic, usually with B symptoms (fever, sweats, weight loss) Lymphadenopathy, hepatosplenomegaly. Symptomatic, usually with B symptoms (fever, sweats, weight loss) Lymphadenopathy, hepatosplenomegaly Most patients are asymptomatic; about 40% with signs (cytopenias, vasculitis, neuropathy, splenomegaly) Treatment approach Observation or immunosuppressive therapy, if required Acute lymphoblastic leukemia-type therapy Acute lymphoblastic leukemia-type therapy Observation or immunosuppressive therapy if required Prognosis Relatively Good Poor Very Poor Relatively Good Source: Williams Hematology, 8th ed, Chap. 96, Table 96–3, p. 1495 +++ Laboratory Features ++ Immunophenotype of LGL cells in blood and marrow: CD3+CD8+CD16+ CD57+ CD4-CD56-, and, often, HLA-DR+. Patients have clonal T-cell–receptor gene rearrangement(s), usually involving α and β chains. Nearly 85 percent of patients have neutropenia, often less than 0.5 × 109/L. Approximately half of the patients have anemia, often caused by pure red cell aplasia and/or autoimmune hemolytic anemia. Approximately one-fifth of patients have thrombocytopenia. About one-quarter of patients do not have increased blood total lymphocyte counts. The median LGL count in patients is 4.0 × 109/L (normal mean 0.3 ×109 /L) ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.