Treatment option for Acute Myeloid Leukemia

Executive Summary

Treatment (acute myeloid leukemia) recommendations depend upon the patient’s state of acute myeloid leukemia. Treatments recommendations depend on the size, grade, and type of tumor, metastasis, possible side effects, and patient’s preferences and overall health. The common treatments for acute myeloid leukemia include intensive chemotherapy (using the intravenous tube, capsule or pill swallowed orally, subcutaneous injection, injection into the cerebral spinal fluid), chemotherapy by phase (induction therapy, blood counts), induction therapy (post-remission therapy, consolidation therapy) targeted therapy, stem cell transplantation or bone marrow transplantation (autologous (AUTO) and allogeneic (ALLO)), radiation therapy (external-beam radiation therapy), and acute promyelocytic leukemia (APL) treatment. Palliative care includes medication, nutritional changes, emotional and spiritual support, and other relaxation therapies. Treatment for recurrent AML includes surgery, chemotherapy, radiation therapy, and targeted therapy.

Treatment for Acute Myeloid Leukemia

“Standard to care” refers to the best-known treatment. In cancer care, a multidisciplinary team where different doctors work together to bring out an overall treatment plan for the patient.

Treatments recommendations depend on many factors:

• The size, grade and type of tumour
• Whether the tumour is applying pressure on vital parts of the brain
• If the tumour has increased to other parts of the body
• Possible side effects
• The patient’s preferences and overall health

Intensive Chemotherapy

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. The chemotherapy type also depends upon the stage. But the point that makes a difference is how the chemotherapy enters the body and which cells it affects.

Chemotherapy is the primary treatment for AML. Systemic chemotherapy enters the bloodstream to reach cancerous cells all over the body. Common ways to give chemotherapy also include ^​1​–

• An intravenous tube is set into a vein using a needle. When chemotherapy is given by IV, it can be given into a larger vein or a smaller vein, such as in the arm. When given into a larger vein, a central venous catheter or port may need to be placed in the body.
• In a capsule or pill that is swallowed (orally)
• Injection under the skin is the subcutaneous injection.
• An injection into the cerebral spinal fluid

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. It can be one drug or a combination of drugs given simultaneously. Chemotherapy for AML is in three phases – induction, post-remission, and consolidation.

Induction therapy

It is the first period of treatment after a person’s diagnosis. And so, the goal of induction therapy is complete remission (CR). A person has a CR when ^​2​:

• Blood counts have returned to normal.
• When seen under the microscope, leukemia is not visible in a bone marrow sample.
• There are no longer any symptoms and signs of AML.

The combination of cytarabine (Cytosar-U) given over 4 to 7 days and an anthracycline drug, like daunorubicin (Cerubidine) or idarubicin (Idamycin), provided for three days is used mainly. Hydoxyurea (Hydrea, Droxia) to help lower white blood cell counts. In addition to killing leukemia cells, these drugs also damage healthy cells, increasing the risk of infection and bleeding. Most patients need to stay in the hospital for around 3 to 5 weeks during induction therapy till their blood counts return to standard. Hence, sometimes, two rounds of therapy are necessary to achieve a CR. About 75% of younger adults with AML and about 50% of patients older than 60 achieve a CR after treatment. While some older adults may not have induction therapy with the standard drugs. Azacitidine (Vidaza), decitabine (Dacogen) and low dose cytarabine can be used instead. A clinical trial can also be an option.

Post-remission therapy

After induction therapy, various drugs aim at destroying the AML cells that remain which remains undetectable in medical tests. AML will almost certainly recur if no further treatment is provided after complete remission. And so, bone marrow/stem cell transplantation is recommended for some patients as part of post-remission therapy ^​3​.

Consolidation therapy

Chemotherapy or stem cell transplantation can be used for consolidation therapy ^​4​. Younger adults in remission typically have 2 to 4 rounds of high or intermediate-dose cytarabine or other intensive chemotherapy at monthly intervals. A bone marrow or stem cell transplantation is can be effective as consolidation therapy for younger patients in whom molecular or cytogenetic studies predict a poor prognosis with only chemotherapy.

Side effects of chemotherapy

Chemotherapy for acute myeloid leukemia attacks rapidly dividing cells, including those in healthy tissues, like the hair, mouth lining, intestines, and bone marrow. People with AML receiving chemotherapy may develop mouth sores, lose their hair, or have nausea and vomiting. Hair will regrow after treatment ends, and there are drugs to help prevent and control nausea and vomiting. The side effects of chemotherapy can be different depending on the drugs used. Patients must to talk to their doctors about short-term and long-term side effects before treatment starts.

However, because of the effect on healthy blood cells present in the bone marrow, chemotherapy used for AML lowers the body’s ability to fight infection for a shorter time, and increased bleeding, bruising, bleeding, and fatigue may be common. People with AML mostly receive antibiotics to prevent and treat infections and will need transfusions of red blood cells and platelets throughout the chemotherapy. Chemotherapy may also affect the patient’s ability to have a child or fertility in the future.

Stem cell Transplantation/Bone marrow Transplantation

A stem cell transplant is a medical process in which bone marrow that contains the cancer is replaced by highly specialized cells. These cells, known as hematopoietic stem cells, develop into the healthy bone marrow. Hematopoietic stem cells are the blood-forming cells found in the bloodstream and the bone marrow. These stem cells form all of the healthy cells in the blood. Presently, this procedure is more commonly called a stem cell transplant than a bone marrow transplant because it is the stem cells in the blood typically being transplanted, not the actual bone marrow tissue.

Before suggesting transplantation, doctors talk to the patient and family members regarding the risks of this treatment. They will also consider several other factors, like age and general health, cancer type, and previous treatment results.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells – autologous (AUTO) and allogeneic (ALLO). AUTO uses the patient’s stem cells, while ALLO uses donated stem cells. In both types, the target is to destroy all cancer cells in the blood, marrow, and other body parts using high doses of chemotherapy or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow.

Side effects depend on the child’s general health, the type of transplant, and other factors.

Targeted Therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. This treatment blocks the growth and spread of tumour cells while limiting damage to healthy cells.

These treatments may be effective for AML, depending on the gene mutations in the leukemia cells ^​5​:

• Ivosidenib (Tibsovo) for people who have relapsed or refractory AML with an IDH1 gene mutation.
• Enasidenib (IDHIFA) for relapsed or refractory AML with an IDH2 mutation.
• Midostaurin (Rydapt) for people with AML with an FLT3 gene mutation. Approximately 25% to 30% of people with AML have AML with an FLT3 gene mutation.
• Gilteritinib (Xospata) for relapsed or refractory AML with an FLT3 gene mutation.

Acute promyelocytic leukemia (APL) treatment

The treatment of the APL subtype of AML is different. This subtype is very sensitive to all-trans retinoic acid (ATRA) effects. ATRA is a drug that resembles vitamin A and is taken orally. People having the APL subtype who receive a combination of ATRA and arsenic trioxide (Trisenox) are most likely to have Complete remission. Less commonly, chemotherapy containing daunorubicin, idarubicin or cytarabine regimens may also be used. Arsenic trioxide can be used during induction therapy alone or combined with ATRA during post-remission therapy or if APL returns after treatment.

Mild to severe bleeding is a typical symptom of APL. Patients with this subtype often need many platelets and blood transfusions during the initial treatment. Compared with other subtypes of AML where maintenance therapy is not used, some patients with APL can benefit from the use of ATRA plus low dose oral chemotherapy for 1 to 2 years after the initial treatment.

Radiation Therapy 

Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. The most common radiation treatment type is external-beam radiation therapy. In this radiation is given from the machine outside the body. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period. AML is mostly present in the blood. And so, radiation therapy is generally used only when leukemia cells have spread to the brain or shrink a myeloid sarcoma. Side effects from radiation therapy can be mild skin reactions, upset stomach, fatigue, and loose bowel movements.

Palliative Care 

Cancer and its treatment have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care. Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies.  Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Refractory AML

If leukemia is still present after initial treatment, then it is refractory AML. If this happens, it is good to talk with doctors who have experience treating it. Doctors can have different opinions about the best standard treatment plan. Also, clinical trials might be an option. 

The treatment plan may also include new drugs that are a part of clinical trials. An ALLO stem cell transplant can also be effective. Palliative care will also be essential to help relieve symptoms and side effects.

For most patients, a diagnosis of refractory leukemia is very stressful and, at times, difficult to bear. 

Remission and chance of recurrence

Remission is when the traces of cancer is not visible in the body and there are no further symptoms.

A remission can be temporary or permanent. Many people worry about the recurrence of cancer. The doctor performs another round of tests to know the extent of the recurrence. Mainly the treatment plan includes the treatments explained above, like surgery, chemotherapy, radiation therapy, and targeted therapy.

Recurrent or relapse is when leukemia returns after the initial treatment. When this occurs, a new testing cycle will start again to learn as much as possible about the recurrence. You may discuss the treatment options with your doctor once, the treatments get over. Often the treatment plan includes the treatments described above, such as chemotherapy, stem cell transplantation, targeted therapy, and radiation therapy. However, it can be in a different combination or pace. Your doctor may suggest clinical trials studying new ways to treat this type of recurrent leukemia. Whichever treatment plan you choose, palliative care is necessary for relieving symptoms and side effects. 

The treatment for recurrent AML usually depends on the length of the initial remission. The initial treatment may work again if the AML comes back after a long remission. If the remission was short, other drugs may be effective. An ALLO stem cell transplant may be the best option for patients whose leukemia has come back after initial treatment. However, many drugs and approaches are under research in clinical trials, providing different treatment options.

Concern and Care

It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.

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