FLAG (chemotherapy)


FLAG is a chemotherapy regimen used for relapsed and refractory acute myeloid leukemia. The acronym incorporates the three primary ingredients of the regimen:
  1. Fludarabine: an antimetabolite that, while not active toward AML, increases formation of an active cytarabine metabolite, ara-CTP, in AML cells;
  2. Arabinofuranosyl cytidine : an antimetabolite that has been proven to be the most active toward AML among various cytotoxic drugs in single-drug trials; and
  3. Granulocyte colony-stimulating factor : a glycoprotein that shortens the duration and severity of neutropenia.
FLAG and FLAG-based regimens can also be used in cases of concomitant AML and either acute lymphoblastic leukemia or lymphoma. Because fludarabine is highly active in lymphoid malignancies, these regimens can further be used when patients have biphenotypic AML, in which cells display properties of both myeloid and lymphoid cells.

Intensified FLAG regimens

There are several intensified versions of the FLAG regimen in which a third chemotherapeutic agent is added.

FLAG-IDA

In the FLAG-IDA regimen, idarubicin—an anthracycline antibiotic that is able to intercalate DNA and prevent cell division —is added to the standard FLAG regimen.

MITO-FLAG

MITO-FLAG adds mitoxantrone to the standard regimen. Mitoxantrone is a synthetic anthracycline analogue that, like idarubicin, can intercalate DNA and prevent cell division.

FLAMSA

FLAMSA adds amsacrine to the standard FLAG regimen. Amsacrine is an alkylating antineoplastic agent that is highly active toward AML, unlike more conventional alkylators like cyclophosphamide.
The FLAMSA protocol is most often used as an induction part of a reduced-intensity conditioning regimen for patients eligible to undergo an allogeneic stem cell transplant. In this setting, it is often combined with other agents, such as: