Treatment options for AML
Treatment for AML needs to start as soon as possible upon diagnosis since it can progress rapidly.
For those with very high numbers of leukemia cells circulating in the blood at the time of initial diagnosis, called leukostasis, problems can arise with normal circulation. Since it takes a few days to lower the number of leukemia cells with chemotherapy, leukapheresis is started first.
The process of leukapheresis involves passing the blood through a machine that removes white blood cells and returns the rest of the blood back to the patient. Two IV (intravenous lines) are inserted. The blood is removed through one, goes through the machine, and is returned to the patient through the 2nd IV.
A single large catheter can be inserted into the neck (central venous catheter or central line) instead, which has both IVs within it.
Several chemotherapeutic agents are effective against AML. The key is to kill off the cancer cells without harming the remaining normal bone marrow cells.
Treatment is divided into two phases: induction of remission and post-remission therapy.
Induction of Remission in Acute Myeloid Leukemia
The first phase of treatment is remission induction or induction therapy with chemotherapy. The aim is to decrease leukemia cells to an untraceable level while bringing back the production of normal blood cells.
In patients under age 60, induction involves the use of:
- Cytarabine (ara-C)
- Anthracycline (e.g. daunorubicin/daunomycin or idarubicin)
A 7 + 3 regimen is one of using cytarabine for 7 days along with short infusions of anthracyclline on each of the first three days.
Patients with poor heart function may not tolerate anthracyclines. Fludarabine (Fludara) or etoposide is then substituted.
Radiation and chemotherapy agents may be inserted into the cerebrospinal fluid (CSF) if leukemia has spread to the brain or spinal cord.
Targeted Therapy Drugs for AML with gene mutations
Drugs directed at distinct parts of cancer cells have been created in recent years. They can be used in tandem with standard chemo drugs or may be helpful if chemo fails.
The FLT3 gene assists cells in making a protein (of the same name) for cell growth. Targeting this protein can help treat these leukemias.
1) Midostaurin (Rydapt)- blocks FLT3 and other proteins on cancer cells involved in cell growth.
-Taken orally twice a day
- Side effects include:
- Nausea, vomiting
- Upper respiratory infections, cough, shortness of breath, chest pain
- High blood sugar levels (hyperglycemia)
- Redness and sores in the mouth
- Muscle or bone pain
2) Gilteritinib (Xospata) blocks FLT3 and other proteins on cancer cells involved in cell growth.
-Taken orally once daily
- Side effects include:
- Redness or sores in mouth
- Muscle or bone pain
- Pneumonia, shortness of breath
- Heart problems, abnormal ECG (electrocardiogram)
- Neurological problems, seizures, confusion
Cells with mutations in IDH1 or IDH2 help make proteins of the same name. These mutations keep blood cells from maturing normally. Targeted drugs that block these proteins enable the leukemia cells to mature or differentiate into normal cells. Thus, these IDH inhibitors are also called differentiation agents.
1) Ivosidenib (Tibsovo) treats AML with an IDH1 mutation recurring after treatment or not responding to traditional treatments.
2) Enasidenib (Idhifa) treats AML with an IDH2 mutation recurring after treatment or not responding to traditional treatments.
- Each taken orally once daily
- Side effects: *
- GI symptoms- nausea, vomiting, diarrhea, loss of appetite
- Joint pain
- Increased levels of bilirubin
- Shortness of breath
* Differentiation Syndrome- an additional side effect of these drugs, occurring in the first treatment cycle when leukemia cells release certain chemicals into the bloodstream.
- Low blood pressure
- Liver or kidney damage
- Fluid buildup around heart or lungs, causing difficulty breathing
Stopping the medication and giving a steroid usually counteracts these symptoms.
An immune protein made to attach to the CD33 protein found on most AML cells. The antibody helps bring the chemo drug to leukemia cells, where it penetrates and kills them when they try to divide into new ones.
Gemtuzumab ozogamicin (Mylotarg) is given with chemotherapy as an initial treatment when CD33 protein is present. Given through an IV, it can be given either with chemotherapy or by itself if other treatments fail to work.
Side effects include:
- Allergic reactions
- Serious or fatal infections, especially with stem cell transplants
- Severe liver damage along with blockage of veins in the liver
- Changes in heart rhythms (arrhythmia)
Venetoclax (Venclexta) targets BCL-2, a life-prolonging protein in cancer cells, and is used in tandem with azacitidine, decitabine, or low-dose cytarabine to treat patients with newly diagnosed AML, those over 75 years of age, and patients who have other medical conditions that prevent use of standard chemotherapy or not aren’t able to withstand strong chemotherapy. It’s taken orally once daily.
Side effects include: *
- Neutropenia (low white blood cells count)
- Anemia (low red blood cell count)
- Thrombocytopenia (low platelet count)
- Nausea, diarrhea
- Pneumonia and other serious infections
*Tumor lysis syndrome (TLS) is a possible side effect of this medication. It occurs more frequently in those with massive numbers of leukemia cells prior to treatment. Drinking plenty of water will help decrease the risk of getting TLS.
When venetoclax Venclexta kills leukemia cells, they break open, and their contents are released into the blood, which can strain the kidneys as they try to eliminate the contents. This can lead to kidney failure. The excess minerals can also lead to heart and nervous system problem. To prevent this, a very lose dose is given initially, and the level is then increased over time.
Hedgehog Pathway Inhibitor
The hedgehog pathway is part of a cell signaling system, which is key in embryo and fetal development as well as some adult cells. AML cells can have mutations in genes that are part of this pathway.
Glasdegib is a drug that attacks a protein in this pathway along with chemotherapy. This drug has proven to increase patients’ longevity.
-Taken orally once daily
- Side effects include:
- Neutropenia (low white blood cell counts)
- Anemia (low red blood cell counts)
- Thrombocytopenia (low platelet counts)
- Muscle and bone pain
- Redness or sores in the mouth
- Cannot take if pregnant
- Must use birth control method during and after treatment
In this phase, there are no leukemia cells in the blood or bone marrow. The bone marrow is functioning properly, and normal amounts of healthy blood cells are now in circulation.
Post-Remission Therapy of Acute Myeloid Leukemia
The key in this phase is to kill undetectable leukemia cells remaining in the bone marrow or blood.
Three treatment options include:
Additional chemotherapy: chemotherapy given after remission is called remission consolidation or post-remission chemotherapy. This is administered over several days and repeated every 4-6 weeks for a duration of 2-6 months. Transfusions are given until the normal blood counts recur. Recuperation can take place at home between treatments.
Allogeneic stem cell transplantation: stem cells are taken from a healthy donor. First, high levels of chemotherapy or radiation are given to kill your stem cells. The replacement stem cells are then injected with the goal of producing blood cells free of cancer.
Autologous stem cell transplantation: your own stem cells are used.
- Loss of appetite
- Weight loss
- Nausea and/or vomiting
- Hair loss
Prognosis: Response to treatment is better when you:
- Have no history of cancer or blood disorders
- Are less than 60 years of age
- Have no chromosomal changes or genetic disorders
- Have a lower white blood cell count on diagnosis
Treatment success and the speed with which leukemia responds determines your long-term prognosis. When initial responses are better, the long-term outcome is better as well.
Remission- no evidence of disease is detected after treatment. The bone marrow is comprised of less than 5% blast cells, the blood count is normal, and there are no symptoms of leukemia.
Complete molecular remission is when there is no evidence of leukemia cells in the bone marrow.
Consolidation Therapy- after remission, despite the lack of detection of leukemia cells, the aim is to cure cancer. At this time, low doses of chemo are administered for months or years. This is also called the maintenance phase.
Minimal residual disease (MRD)- leukemia cells can no longer be detected in the bone marrow using a microscope, but some evidence of them lingering in the bone marrow are seen with more sensitive tests like the flow cytometry or PCR.
Active disease- leukemia is still present during treatment or has returned after treatment (relapse). A relapse is when there are more than 5% blast cells in the bone marrow post treatment.
Follow-up care is crucial to ensure there is no recurrence. Checkups every few months with blood tests will catch a new attack early.
The good news is that AML doesn’t usually return if you are free from it for a few years.
The following helps relax patients during treatment and enables them to tolerate the chemotherapy better:
- Meditation- eases stress
- Yoga- relaxes muscles, eases stress
- Acupuncture- provides pain relief
- Massage- releases muscle tension
- Breathing exercises- induces relaxation
- Biofeedback- helps release tension