LGL Syndrome / LGL Leukemia (Large Granular Lymphocyte (LGL) Syndrome, T-Cell Granular Lymphocytic Leukemia, Large Granular Lymphocyte (LGL) Leukemia).

ICD-10: C91.5

Definition

LGL syndrome is defined as a neoplastic disease (REAL classification) with chronically increased number of large granular monoclonal lymphocytes (white blood cells) (CD3 + cytotoxic NK cells) in blood and bone marrow. The disease was first described in 1985 and is separated from the much more aggressive NK cell leucemia.

Disease Cause

Unknown cause.

• Most have too
  • Rheumatoid arthritis (The disease picture overlaps in part with Felty's syndrome) (reference: Wlodarski MW, 2006)
  • SLE or
  • Sjögren's syndrome (Reference: Friedman J, 2006)

Occurrence

• Men and women
• Most commonly aged 12 - 87 years, median 60 years of age

Symptoms and results of medical examination

get symptoms. Often random discovery by medical examination of recurring infections

• The most common are:
  • Splenomegaly (large spleen) (25-50%)
  • Anemia (low hemoglobin in the blood) (erythroid hypoplasia)
  • Neutropenia (few neutrophils of white blood cells)
  • Recurring infections (at 50%)
  • Rarely enlarged lymph nodes
• Associated diseases present concurrently with LGL leukemia (40-60%):
  • Rheumatoid arthritis (RA) occurs among 11-36%
  • Sjögren's syndrome
  • SLE (Systemic lupus erythematosus)
  • Myositis
  • Polymyalgia rheumatica
  • Vasculitis diseases
  • Other

Blood tests

Lymphocytosis (2-20 x 10⁹/ L), neutropenia, anemia, hypergammaglobulinemia, Antibodies, Circulating immune complexes.

Bone marrow

Often affected, but to varying degrees.

Diagnosis

• Measurement of neutrophil leukocytes (typical discovery: 0,4-2,9 x 10⁹/ L).
• Bone marrow aspirate or biopsy with immunohistochemistry.

Incorrect diagnosis? (Similar diseases / differential diagnoses)

• Viral infections and Autoimmune diseases (Transient or chronically increased polyclonal T-cell or NK-cell lymphocytosis)
• Older persons (oligoclonal and small monoclonal CD3 + LGL cells)
• After transplants (Oligoclonal and small monoclonal CD3 + LGL cells)
• Felty's syndrome (by Rheumatoid arthritis)

Genetically: Clonal changes in T-cell receptors exist. In the gene for the T-cell β chain, more frequent changes than the chain are present.

Treatment

Not all cases require treatment. If severe or symptomatic neutropenia, anemia or rheumatoid arthritis (RA) a low dose methotrexate or Cyclophosphamide (Sendoxan) as initial treatment are options. Alemtuzumab has been used in refractory cases.

Treatment response can be evaluated after 4 months: Normalization of cell counts (Hemoglobin over 12 g / 100mL, platelets over 150 x 10⁹/ L, neutrophilic leukocytes over 1,5, lymphocytes under 4 and circulating LGL normalized). By PCR examination T-cell clones can be measured (should be gone by complete remission). Steroids (Prednisolone) have a disappointing effect outside of temporary symptom improvement. (Reference: Lamy T, 2011)

Medical prognosis

No curative treatment, but generally good prognosis. 5 Year Survival 89%

Literature

• Michalsen S, 2009

---

• Bindevevssykdommer.no
• Vaskulitt.no