Aggressive large granular lymphocytic leukaemia (LGLL)

Aggressive LGLL is a fast developing and life-threatening type of LGLL. It is very rare. This page will tell the signs and symptoms, how it is diagnosed and what treatment you can expect to have.

Aggressive LGLL is a rare type of blood cancer. It is life threatening without treatment. Active monitoring is rare and you are likely to have immediate treatment.

Patients affected by aggressive LGLL are usually:

  • Young Asian patients (median age of 40 years)
  • Patients with a previous Epstein-Barr virus infection. The Epstein Barr virus is virus associated with mononucleosis. Mononucleosis is also known as glandular fever

What are the signs and symptoms of aggressive LGLL?

Symptoms of aggressive LGLL are:

  • Unexplained weight loss greater than 10% of body weight in the previous six months
  • Severe fatigue (unable to work or perform usual activities)
  • Fevers greater than 38°C (100.5°F) for at least two weeks with no infection
  • Drenching night sweats for more than a month without having an infection
  • Enlargement of the lymph nodes around the body
  • Enlargement of the liver and spleen

How is aggressive LGLL diagnosed?

Diagnosis of aggressive LGLL requires:

  • If previous blood tests are available, the presence of clonal LGLL cells in the blood for more than six months
  • Levels of NK‑LGLL cells greater than 0.5×109/L (normal range: 0.25×109/L).
  • Symptoms of aggressive LGLL
  • Distinct CD proteins on the LGLL cells: CD3-, CD4-, CD8-, CD16+, CD56+ and CD57-
  • Gene mutations in the STAT3 gene, STAT5B gene and TNFAIP3 gene. The STAT5B mutation regarded as the signature mutation

How is aggressive LGLL treated?

You are likely to have immediate treatment given the aggressive nature of LGLL. Treatment options for aggressive LGLL resemble those for chronic LGLL. They include immunosuppressants, immunotherapy, or chemotherapy combinations (fludarabine, cladribine and bendamustine).

There is no standard treatment for aggressive LGLL. This is because of the small number of patients with aggressive LGLL. Most haematologists report any cases and the treatments they have used. Experience from these case reports have suggested the following conclusions:

  • Chemotherapy combinations have not been successful in aggressive T-cell LGLL
  • Patients with a complete remission should receive an allogeneic stem cell transplant, this offers the best outcome
  • Frontline treatment for aggressive NK-cell LGLL is:
    • Haematologists use L-asparaginase either alone or combined with chemotherapies. These chemotherapies include as cyclophosphamide, doxorubicin, vincristine and cytarabine
  • Your haematology team will schedule an allogeneic stem cell transplant

What is the prognosis for aggressive LGLL?

Overall survival with aggressive LGLL is around two to three months. Despite the poor overall prognosis, patients who reach remission show a better prognosis and survival.

The poor prognosis for patients with aggressive LGLL is due to:

  • Aggressive LGLL cells that are uncompromising
  • Poor response to treatment with few treatment options

Want to know more about LGLL?

You can find more information about LGLL in our free information booklet, download your copy here. If you’d rather read the booklet in smaller bitesize pieces of information, download our LGLL factsheet here.

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    Page published on: 15th August 2022