Treatment Name: FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin)
FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin) is a Chemotherapy Regimen for Acute Lymphoid Leukemia (ALL)
How does FLAG-IDA chemotherapy work?
Each of the medications in the FLAG-IDA chemo regimen are designed to target and kill leukemia cells in the blood and bone marrow.
FL - Fludarabine
A - Ara-C (Cytarabine)
G - Granulocyte colony stimulating factor (G-CSF, filgrastim)
IDA - Idarubicin
Goals of therapy:
FLAG-IDA is given as induction chemotherapy to eliminate leukemia cells from the body and to decrease symptoms from ALL, such as bleeding, bruising, and recurrent infections. It may be given with the goal of cure or to put the leukemia in remission so a bone marrow transplant can be performed.
How is FLAG-IDA therapy for ALL given?
- Fludarabine intravenous (I.V.) infusion over 30 minutes on Days 1, 2, 3, 4 and 5
- Cytarabine I.V. infusion over four hours (starting four hours after fludarabine) on Days 1, 2, 3, 4 and 5
- Idarubicin intravenous push over 10 - 15 minutes on Days 1, 2 and 3
- G-CSF (Filgrastim) subcutaneous injection once daily starting 24 hours either the day before or the day of chemotherapy, and continuing daily until Day 5. In some instances, G-CSF may be restarted seven days after chemotherapy and continued until the neutrophil count returns to normal range
Estimated total infusion time for this treatment:
- Up to five hours on Days 1 through 5; however, since fludarabine and cytarabine must be separated by four hours, it can take up to 9 hours to finish treatment each day
- Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time
A bone marrow biopsy is usually performed after treatment when white blood cells return to normal range to see if the leukemia is in remission. This may occur as early as Day 14, but some doctors prefer to wait until sometime between Day 21 to 28.
FLAG-IDA requires a 21 to 28 day stay in a hospital (sometimes longer) depending upon when white blood cell counts return to the normal range and also how well the side effects are tolerated and whether remission is achieved.
Only one cycle of FLAG-IDA is typically given; however, if remission is achieved, a second cycle of FLAG-IDA or a different chemotherapy regimen may subsequently (next) be given to obtain a deeper (better) response.
Click here for the common FLAG-IDA starting doses.
What are the most common side effects from FLAG-IDA for ALL?
In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported drug side effects of FLAG-IDA are shown here:
- Infection (78%)
- Sores in mouth and on tongue (78%)
- Increased blood bilirubin [sign of liver injury] (26%)
- Skin reaction (22%)
- Increased liver enzymes in blood [sign of liver injury] (17%)
- Nausea and vomiting (17%)
- Bleeding (13%)
- Increased blood creatinine [sign of kidney injury] (9%)
While the exact percentage was not reported in clinical trials, nearly all patients experience low red blood cells (Anemia), low white blood cells (neutropenia), and low platelets (thrombocytopenia).
Importantly, not all people who experience a side effect from FLAG-IDA will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid treatment with a certain medication altogether.
Side effects may be treatable when they occur or preventable by taking certain medications before they happen. When medications are taken to prevent a problem, this is known as prophylaxis, or "prophy" for short.
After starting treatment with FLAG-IDA, be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.
Watch videos on common FLAG-IDA therapy side effects below
How often is monitoring needed?
Labs (blood tests) may be checked before treatment, then daily or every other day for the first few weeks while in the hospital. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), lactate dehydrogenase (LDH), phosphorous, and uric acid, plus any others your doctor may order.
How often is imaging needed?
Imaging may be checked before treatment, or during the first month if there is concern for an infection or blood clot. Imaging may include: X-rays and computerized tomography (CT) scans. An echocardiogram or multigated acquisition (MUGA) scan may be performed before treatment to check your left ventricular ejection fraction (LVEF).
How might blood test results/imaging affect treatment?
Depending on the results of the bone marrow biopsy, your doctor may choose to continue therapy, change therapy, or not give you any more therapy and observe you closely.
What are the most important things to know about FLAG-IDA while receiving treatment?
- During the first few days of therapy, you will be monitored closely for tumor lysis syndrome (TLS). Signs of TLS are high levels of potassium, phosphorous and uric acid and low levels of calcium in the blood. Allopurinol is a medication commonly given at the start of therapy to prevent the development of high uric acid levels in the blood. Additional medications may need to be given if TLS develops
- Corticosteroid eye drops, such as prednisolone eye drops, are often started before the first dose of cytarabine to prevent eye irritation known as conjunctivitis. Eye drops may be continued 48 to 72 hours after the last dose of cytarabine
- Short term difficulty with writing, walking, or talking may occur but is rare and usually reversible. To prevent these problems, various neurological tests are done prior to each dose of cytarabine looking for early signs of toxicity. Examples of these tests include: follow an object with your eyes, repeat various phrases, sign your name, or walk a straight line
- FLAG-IDA requires a long stay in the hospital. Try to be as active as possible by taking walks in the hallway, or using an exercise bicycle in the room, if available. This will hopefully speed time to recovery
- An anti-fungal medication, such as posaconazole, may be prescribed to prevent a life-threatening invasive fungal infection
- Reactivation of herpes simplex virus (HSV) can occur. Prophylactic (preventative) anti-viral medications such as acyclovir (Zovirax®), valacyclovir (Valtrex®), or famciclovir (Famvir®) should be taken during treatment
- A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- Clinical trials may exist for AML. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications
Patient Assistance & Co-payment Coverage
Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin), we have provided links that may help.
Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin). Depending upon your income, they may be able to help cover the cost of:
For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.
- If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.
Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin) and are the best source to help you understand drug cost.
- Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.
What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.
Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.
Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.
Learn more about pursuing emotional wellness while receiving treatment with FLAG-IDA (Fludarabine + Ara-C + G-CSF + Idarubicin)
What is Acute Lymphoid Leukemia (ALL)?
Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.
Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.
NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose your therapy.
What is Induction Chemotherapy?
An intensive cycle of chemotherapy that requires hospitalization. Induction chemotherapy often requires intense monitoring by hospital staff to ensure that infections are treated and blood or platelet transfusions are given when needed. The goal of induction chemotherapy is to achieve a complete remission, meaning no leukemia cells are detectable.
What does Cure mean?
The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, doctors use the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.
Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.
What is an I.V. Push?
An intravenous medication that is usually prepared in a syringe and infused by vein over a short period of time, such as 15 minutes or less
If you are interested in reading the clinical trials results, please click on references below:
1) Specchia G, Pastore D, Carluccio P, et al. FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia. Ann Hematol 2005;84:792-795
What is a CBC?
A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.
2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.
3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.
What is a CMP?
A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status, 2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.
Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
13) Serum glucose
14) Serum calcium
What is the Left Ventricular Ejection Fraction (LVEF)?
The amount of blood pumped by the left ventrical (chamber) of the heart into the body with each heartbeat. Certain drugs can decrease heart function and result in less blood being pumped by each heartbeat than normal.
What is Tumor Lysis Syndrome?
Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.
What if a bicycle is not available? Some hospitals allow family members to purchase an exercise bicycle and bring it in fully assembled. Ask your nurse if this may be an option!
Common FLAG-Ida starting doses
- Fludarabine 30 mg/m2 intravenous (I.V.) infusion over 30 minutes on Days 1, 2, 3, 4 and 5
- Cytarabine 2000 mg/m2 I.V. infusion over 4 hours (starting 4 hours after fludarabine) on Days 1, 2, 3, 4 and 5
- Idarubicin 10 mg/m2 intravenous push over 10 - 15 minutes on Days 1, 2 and 3
- G-CSF (Filgrastim) subcutaneous injection once daily starting 24 hours either the day before or the day of chemotherapy, and continuing daily until Day 5. In some instances, G-CSF may be restarted 7 days after chemotherapy and continued until the neutrophil count returns to normal range
Posaconazole is an anti-fungal medication that has been shown in a large, randomized clinical trial to prevent life-threatening fungal infections in patients with AML receiving induction chemotherapy