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Chapter 57: Large Granular Lymphocytic Leukemia

DEFINITION

  • T-cell large-granular lymphocytic (T-LGL) leukemia results from the clonal expansion of large granular lymphocytes (LGLs) 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. (See Chap. 66.)

T-LGL LEUKEMIA

Etiology and Pathogenesis

  • There is 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.

  • Leukemic cells have features of antigen-activated cytotoxic T lymphocytes, suggesting a 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 (eg, neutropenia, rheumatoid arthritis).

Clinical Features

  • About half of patients have palpable splenomegaly. (Table 57–1)

  • About one-third of patients have recurrent bacterial infections.

  • “B symptoms” (eg, low-grade fevers, night sweats, and/or weight loss) (aggressive variant) are very infrequent.

  • About one-fourth of patients have rheumatoid arthritis, often with features of “Felty syndrome.”

  • Less than one-tenth of patients have lymphadenopathy.

TABLE 57–1CLINICAL FEATURES OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA
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TABLE 57–1CLINICAL FEATURES OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA
...
  Pandolfi (1990) Loughran (1993) Dhodapkar (1994) Semenzato (1997) Neben (2003) Bareau (2010)
Number of patients 151 129 68 162 44 201
Median age 55 57 61 59 63 59
Male/Female 1.3 0.8 1 0.8 1.0 0.8
Symptomatic 72% – 69% – 73% 82%
Splenomegaly 50% 50% 19% 50% 35% 24%
Hepatomegaly 34% 23% 1% 32% – 10%
Adenopathy 13% 1% 3% 13% 5% 6%
B symptoms – – 12% – – 7%
Infections 38% 39% 15% 56% – 23%
Rheumatoid arthritis 12% 28% 26% 36% 20% 17%
Rheumatoid factor – 57% 61% 43% 48% 41%
Antinuclear antibodies – 38% 44% 38% 48% 48%
Autoimmune cytopenias – – 7% 9% 5% 7%
Lymphocytosis 29%
LGL > 4 × 109/L 52% 52% – – – 14%
LGL 1–4 × 109/L 38% 40% – – – 50%
LGL < 1 × 109/L 10% 8% – 7% – 36%
Neutropenia
Moderate (< 1.5 × 109/L) 64% 84% 74% – 52% 61%
Severe (0.5 × 109/L) 7% 48% 40% 37% 41% 26%
Anemia
Any severity 25% 49% 51% 26% 89% 24%
Severe (Hgb < 8 g/dL) 37% – 19% – 36% 7%
Thrombocytopenia 9% 19% 20% 29% 36% 19%
LGL marrow infiltration 67% 88% – 76% 83% 72%
Hypergammaglobulinemia – 45% 5% 43% – 35%
Monoclonal gammopathy – 45% 8% – – 10%
Need for treatment 30% 73% 69% 33%

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