About AML (Acute Myelogenous Leukemia)

AML is one of the most common types of leukemia in adults. The American Cancer Society’s most recent estimates are about 13,780 new cases in the US, mostly in adults. About 10,200 deaths will be from AML for the year 2012.   The average age of a patient is about 67 and it affects more men than women. Although AML is a relatively rare disease, accounting for about 1.2% of cancer deaths in the US, its incidence is expected to increase as the population ages. AML progresses rapidly and is typically fatal within weeks or months if left untreated.

Normal healthy white cells that fight infection have a short life span and are continually made in the bone marrow. When they die they are replaced with new cells. Specialized white blood cells called granulocytes and monocytes are damaged in ALL in such a way that they cannot mature beyond an early stage of their life cycle. Over time these blasts (immature cells) take over the bone marrow and displace the normal red and white blood cells and platelets. As the numbers of normal cells decrease patients may develop anemia, infections, bruising and bleeding from the low levels of platelets.

Risk Factors
There is only a small chance that a person who has a known risk factor for AML will develop the disease. Some of the risk factors are smoking, exposure to high levels of radiation or certain chemicals at work (such as benzene), or having some types of chemotherapy to treat another cancer can put you at higher risk for developing leukemia.

Symptoms
The symptoms for acute leukemia can appear suddenly and be similar to a flu or virus.

  • Fever, headache
  • Loss of weight and/or appetite
  • Easy bruising and/or bleeding
  • Weakness and fatigue
  • Night sweats
  • Coughing, shortness of breath
  • Frequent minor infections or poor healing of minor cuts
  • Swollen lymph nodes, stomach, head, arms and gums
  • Tiny red spots on the skin
  • Bone or joint pain
  • Difficult maintaining balance
  • Blurred vision
  • Seizures, vomiting
  • An enlarged testicle with no pain

Diagnosis
In order to diagnose leukemia your doctor will ask you questions about your past health and symptoms. Your doctor will do a physical exam, will look for swollen lymph nodes and check to see if your liver or spleen is larger than normal. Blood tests will be ordered to check to see if your white blood cells are high and your other blood cells levels are low. If you have abnormal blood tests then your doctor may do a bone marrow biopsy. This test will look at the inside of your bone. A sample of your blood or bone marrow will be tested for abnormalities in your genes to tell the difference between ALL and AML. Imaging such as a CT scan, MRI or ultrasound can find out if other organs such as the lung, liver, spleen, lymph nodes, brain and kidneys have been affected as well.

Classification
Most cancer types are assigned a numbered stage based on the size of the tumor and how far it has spread. Leukemia is not staged that way.

Two systems have been used to classify AML into subtypes – the French-American-British (FAB) system and the new World Health Organization (WHO) system.

  • The French-American-British (FAB) classification of AML

AML is divided into subtypes M0 through M7, based on the type of cell from which the leukemia started and how mature the cells are. The system is based largely on how the leukemia cells looked under the microscope and the symptoms the person has. Now doctors use many advanced gene tests to classify AML. Knowing the type helps the doctor plan treatment. Most types of AML are treated the same way except for patients with M3. That is called acute promyeolocytic leukemia (APL). APL needs a different treatment plan. Your doctor will order a test called flow cytometry to find out the type of AML that you have. The FAB system is the one most often used to group AML into subtypes. But it doesn’t take all of the prognostic factors described below into account. 

Prognostic Factors
There are differences among patients that affect the response to treatment which are called prognostic factors. These include a patient’s age, white blood cell count, certain gene test results and if the person has had chemotherapy or radiation therapy in the past for another cancer.

  • World Health Organization (WHO) classification of AML

The WHO system tries to help better classify cases of AML based on a patient’s outlook. Not everyone uses this system.

How well a patient responds to treatment has an effect on the long-term outlook for the patient. A remission can be complete (no signs of the disease after treatment), or molecular complete (even very sensitive tests cannot find leukemia cells in the bone marrow).

Minimal residual disease is a term used after treatment when leukemia cells can’t be found in the bone marrow using standard tests, but more sensitive tests can still find some cells.

Active disease means that either the leukemia is still present during treatment or it has come back (relapsed) after completing treatment. Patients must have more than 5% blast cells present in the bone marrow to relapse.


Treatment Options
The goal of treatment for AML is to cure the disease. Almost 50% of children diagnosed with AML will be cured. Patients with APL have higher cure rates compared to adults with other AML subtypes. Some adults with AML will have long periods of remission or will be cured. The initial goal of treatment is to get the patient into remission.

Treatment is divided into several phases:

Induction chemotherapy brings the bone marrow into remission by reducing the number of leukemic cells to an undetectable level. Standard induction chemotherapy usually includes cytarabine (ara-C) (a medicine called an antimetabolite which slows or stops the growth of cancer cells) and an anthracycline such as daunorubicin or idarubicin (a type of antibiotic that damages DNA in cancer cells). This is given as a continuous IV infusion for seven days (the medicine goes directly into the vein through a thin tube and stays in place for the seven days) while the anthracycline is given for three days as an IV push (medicine given all at once over a few minutes directly into the vein)Up to 70% of patients will go into remission with this protocol. Other medications that can be used include high-dose cytarabine alone or investigational agents (a medicine that is being used in clinical research and has not yet been approved by the Food and Drug Administration) may also be used. Because of the toxic effects of therapy, including myelosuppression (a condition where the bone marrow activity is decreased resulting in fewer red blood cells, white blood cells and platelets)  and an increased risk of infection.Induction chemotherapy may not be offered to the very elderly, and the options may include less intense chemotherapy or palliative care.

There is a certain subtype of AML, known as acute promyelocytic leukemia (APL), usually treated with the drug all-trans-retinoic acid (ATRA) in addition to induction chemotherapy, usually an anthracycline. APL is curable, with well-documented treatment protocols.

The goal of the induction phase is to reach a complete remission. Complete remission does not mean the disease has been cured; rather, it means that no disease can be detected. Complete remission is obtained in about 50%–75% of newly diagnosed adults. The length of remission depends on the original leukemia. 

Consolidation therapy is used to remove any remaining leukemia cells. Patients will typically undergo an additional three to five courses of intensive chemotherapy. For patients at high risk of relapse allogeneic stem cell transplantation is usually recommended if the patient is able to tolerate a transplant and has a suitable donor. Three years after this treatment about 45% of patients younger than 60 will not show any signs of leukemia. Doctors will recommend the treatment for consolidation based on several factors.

Some of these include how much chemotherapy it took to go into remission, whether or not there is a stem cell donor, if leukemia free bone marrow cells can be collected from the patient, the patient’s age and what the patient would like to do.

For patients over the age of 60 who are healthy, they may be treated the same way as younger patients. Patients who are in poorer health or are much older their doctors may recommend less intense treatment or they may choose supportive care. Their focus may be on treating symptoms or problems as they occur to keep the patient as comfortable as possible.

Relapsed AML:  For patients with relapsed AML, the only potentially curative therapy is a stem cell transplant using healthy stem cells that are removed from someone else and put into a patient to treat their AML, if one has not already been performed.
Patients with relapsed AML who are not candidates for stem cell transplantation, or who have relapsed after a stem cell transplant, may be offered treatment in a clinical trial, as regular treatment options are limited. Agents under investigation include clofarabine, a cytotoxic drug that works by removing malignant cells in the body, and also stops the healthy cells from creating new RNA and DNA, thus preventing new cells from being created. There are targeted therapy drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression.  Since treatment options for relapsed AML are so limited, palliative care may be offered. For relapsed acute promyelocytic leukemia (APL), arsenic trioxide which is a natural compound that has been used for many years has been tested in trials and approved by the Food and Drug Administration. Like ATRA, arsenic trioxide does not work with other subtypes of AML.
Maintenance involves giving a low dose of a chemo drug for months or years after consolidation is completed. This is often used for AML M3, but it is rarely used for other types of AML.

Acute promyelocytic leukemia (APL or AML M3) is different from other types of AML. The leukemia cells contain proteins that, when released into the bloodstream, cause the blood to clot in an out of control way. This can cause bleeding problems as well as clotting problems. In the past patients sometimes died from complications related to the problems with clotting.

There are now newer drugs that can fight APL without leading to those clotting problems, Drugs such as all-trans-retinoic acid (ATRA, tretinoin or Vesanoid®) and arsenic trioxide (ATO, Trisenox®). These drugs are only used for APL.

Radiation therapy (or radiotherapy) is used on painful bony areas, and in areas where there is a large mass in a local area or as part of the preparations for a bone marrow transplant (total body irradiation).

Allogeneic (using donor stem cells) and autologous (using the patient’s own stem cells) bone marrow transplantation may also be appropriate for high risk or relapsed patients. Clinical trials may be an option for some people. Clinical trials are research projects that test new medicines and treatments. Many people with leukemia take part in clinical trials.

 

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