Aggressive large granular lymphocytic leukaemia (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

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

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

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