FLAG is a

chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combina ...

used for

relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or ...

d and

refractory In materials science, a refractory material or refractory is a material that is resistant to decomposition by heat, pressure, or chemical attack, and retains strength and form at high temperatures. Refractories are polycrystalline, polyphase, ...

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...

(AML). The

acronym An acronym is a word or name formed from the initial components of a longer name or phrase. Acronyms are usually formed from the initial letters of words, as in ''NATO'' (''North Atlantic Treaty Organization''), but sometimes use syllables, as ...

incorporates the three primary ingredients of the regimen: # Fludarabine: an

antimetabolite An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolate ...

that, while not active toward AML, increases formation of an active cytarabine metabolite, ara-CTP, in AML cells; # Arabinofuranosyl cytidine (or ara-C): an antimetabolite that has been proven to be the most active toward AML among various

cytotoxic drugs Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

in single-drug trials; and # Granulocyte colony-stimulating factor (G-CSF): 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 (ALL) or

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

. 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 The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...

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 (also called FLAG-Ida, IDA-FLAG, or Ida-FLAG),

idarubicin Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy ...

—an

anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder canc ...

antibiotic that is able to

intercalate Intercalation may refer to: *Intercalation (chemistry), insertion of a molecule (or ion) into layered solids such as graphite * Intercalation (timekeeping), insertion of a leap day, week or month into some calendar years to make the calendar foll ...

DNA and prevent

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

( mitosis)—is added to the standard FLAG regimen.

MITO-FLAG

MITO-FLAG (also called Mito-FLAG, FLAG-MITO, or FLAG-Mito) adds mitoxantrone to the standard regimen. Mitoxantrone is a synthetic anthracycline analogue (an

anthracenedione Anthraquinone, also called anthracenedione or dioxoanthracene, is an aromatic hydrocarbon, aromatic organic compound with formula . Isomers include various quinone derivatives. The term anthraquinone however refers to the isomer, 9,10-anthraquinon ...

) that, like idarubicin, can intercalate DNA and prevent cell division.

FLAMSA

FLAMSA adds amsacrine ("AMSA") to the standard FLAG regimen. (G-CSF is still included, even though the "G" is taken out of the acronym.) Amsacrine is an

alkylating antineoplastic agent An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA. The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring. Since ...

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: * Cyclophosphamide (FLAMSA-CYC), and/or *

Busulfan Busulfan (Myleran, GlaxoSmithKline, Busulfex IV, Otsuka America Pharmaceutical, Inc.) is a chemotherapy drug in use since 1959. It is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Its chemical ...

treosulfan Treosulfan, sold under the brand name Trecondi, is a medication given to people before they have a bone marrow transplant from a donor known as allogeneic hematopoietic stem cell transplantation. It is used as a 'conditioning' treatment to clea ...

(FLAMSA-BU or FLAMSA-TREO), and/or *

Melphalan Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and AL amyloidosis. It is taken by mouth or by injection into a vein. Common side effects incl ...

(FLAMSA-MEL), and/or * Total body irradiation, given shortly after the end of FLAMSA to prepare the patient for transplant.

Intensified FLAG regimens

FLAG-IDA

MITO-FLAG

FLAMSA

Dosing

Standard FLAG

FLAG-IDA

Mito-FLAG

FLAMSA

References