Chapter 58: Large Granular Lymphocytic Leukemia

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.

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).

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 58–1COMPARATIVE FEATURES OF LARGE GRANULAR LYMPHOCYTIC LEUKEMIA

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

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) (Fig. 58–1...

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