I have a patient with LGL and associated neutropenia. He's ANC continues to be below 500 (most recently 200.) I've had him on MTX weekly dosing that I've gone form 10 mg/m2 to 15 with no improvement. I've done courses of prednisone tapers that transiently improve his counts but for brief periods of time. He's never had an infection but I'm concerned with the prolonged periods of neutropenia and was hoping to hear your thoughts on other possible treatment options?
How long has the patient been on MTX thus far? There may be long times to MTX response among LGL patients, with some LGL patients taking as long as 3-4 months to demonstrate response. It is therefore difficult to say that a patient has failed MTX until they have been on the drug for at least 3-4 months. If the patient has not yet been on MTX for 3-4 months, would continue MTX for now and continue to reassess (w/ plan to discontinue MTX and switch to alternate agent if no response by the 3-4 month mark). In the meantime, if there is concern re infectious risk in s/o persistent severe neutropenia, would consider initation of ppx antimicrobials (such as levofloxacin 500mg daily + acyclovir 400mg bid +/- fluconazole 200mg daily) if not on them already. Additionally, courses of GCSF may be trialed to support the ANC until an adequate time has passed to better assess response to MTX. If the patient has been on MTX for 3-4 months and demonstrated inadequate response would then switch to an alternate agent. The most evidence based next lines of therapy would be cyclophosphamide or cyclosporine. If there has been inadequate response after 3-4 month trial of MTX would switch to one of these therapies. Would discuss relaitve risks and benefits of these 2 treatments with the patient in order to decide which to pursue next. GCSF may be administered concurrently (as above) to support ANC until sufficient time has past for response assessment (as times to response with these agents may also be somewhat long). If one of these agents fail would then try the other.
