Would you offer next-line systemic therapy to a patient with LGL leukemia with chronic severe neutropenia, who has had treatment failure with methotrexate, cyclophosphamide, cyclosporine, and danazol?

Response can be slow and delayed. Treatment failure is usually considered after 4 months of therapy. Steroids can be used with methotrexate in severe neutropenia with a slow taper over 4-6 weeks. This strategy seems to potentiate the effect of methotrexate.

Evidence after these therapies is limited....

I have a young patient with LGL, with ANC count hovering between 300-600 without treatment for a number of years. She has done well. I think it would be reasonable to have a trial of observation alone.