The treatment of acute myeloid leukemia is quite challenging, with various considerations that need to be taken to tailor therapeutics and achieve the best results. In many cases, results can vary widely depending on age, the agents used and the overall health of the patients. Also, the risk of recurrence should be taken into account. Some chemotherapy regimens are associated with a higher risk of recurrence than others. Other drugs need the presence of a certain antigen or “marker” before their administration; the so-called “targeted therapy”. Finally, the treatment of acute promyelocytic leukemia, which is a subtype of acute myeloid leukemia, can vary from the usual regimens.
Treatment options for AML
The mainstay of treatment of acute myeloid leukemia is chemotherapy, it is used as an induction treatment for a few days, followed by consolidation treatment -that may or may not include chemotherapy- to reduce the risk of recurrence.
A) Induction therapy:
The most commonly used chemotherapy for induction is called the “3 and 7 regime”. It includes an intravenous infusion of anthracycline for 3 days in combination with 7 days of cytarabine. Cytarabine acts by preventing DNA from replicating, which is a key step in cell multiplication seen in cancers, while anthracyclines are a group of drugs that act on an enzyme called topoisomerase II which is a key enzyme in DNA replication through preventing the DNA from “winding around itself”. The most commonly used drug in the anthracycline family is daunorubicin. The main drawback of chemotherapy is that it is not suitable for frail patients and optimal body systems are needed to withstand their toxicity. Old and weak patients may have a higher risk of side effects, and all of these drugs are toxic to the bone marrow, especially because high doses may be needed in non-responders.
Other options for induction include targeted therapy as Midostaurin, which targets a certain mutation in cancer cells and acts against multiple enzymes. It proves beneficial when used with the standard chemotherapy during induction. Also, Cladribine is used as a catalyst for cytarabine since it increases the amount of cytarabine intake into cancer cells, increasing its efficacy.
B) Consolidation treatment:
Consolidation therapy is highly controversial, and if you are younger than 60 years old, your doctor might talk to you about bone marrow transplantation as a better option. However, multiple studies have shown that good initial response in the induction period can spare the patient a bone marrow transplantation by using cytarabine as a chemotherapy in high doses. The idea of avoiding bone marrow transplantation is that it always carries the risk of rejection, infections or even a slight risk of life-threatening complications. The availability of a compatible donor is also important, but recent studies show an opportunity by using autologous bone marrow transplantation.
The idea of autologous transplantation is that we can use the cells of the same patient after successful chemotherapy as a graft after ablating their bone marrow by chemotherapy or radiation. The choice of bone marrow transplantation vs chemotherapy is, however, not that simple and many factors play a role, most importantly the genetic component of the cancer.
How are old people treated if chemotherapy is risky?
As mentioned before, traditional chemotherapy may not be the best option for old individuals suffering from AML. Up until 2018, old patients had a bad outcome because of poor regimens and side effects from the effective ones, until the FDA approved ventoclax. This drug was originally designed for lymphoma, but it showed a remarkable effect on acute leukemia since the same protein found in lymphoma was also found in leukemia cells. It is used in combination with other drugs such as decitabine and azacytidine, and the combination has a far better adverse effects profile, although not as effective as the ones used in younger individuals.
Stem cell transplantation is a hot topic in these patients and no clear recommendations approve or disprove its effects. Generally speaking, it benefits old but fit individuals and has different techniques than the one used in younger patients, but with lower success rates.
Treatment of acute promyelocytic leukemia
Promyelocytic leukemia is different from normal acute myelocytic leukemia in its cellular composition, and the genetic defect responsible for its formation. For that reason, this treatment has some differences than the standard therapy for acute myeloid leukemia. For instance, All-trans-retinoic acid is considered a cornerstone in its management with the chemotherapy regimens.
Also, since the risk of life-threatening hemorrhage is much higher in acute promyelocytic leukemia, patients should be monitored more closely and supportive therapy of transfusions should be meticulously given to those patients to avoid their mortality. Arsenic trioxide may also be given both for induction and consolidation therapy.
Other measures
1) Blood transfusion:
Because patients with acute leukemia have a defective bone marrow due to its invasion by the abnormal blast cells, they may need replacement therapy for blood components. Red blood cells may need to be transfused if anemia develops and platelets may also fall in number and need transfusion to avoid life-threatening hemorrhage.
2) Management of infections:
Despite the fact that leukemia patients have an elevated white blood cell count, their immune systems are weak because those cells are not functioning. In fact, those cells are overcrowding the bone marrow, and healthy cells are produced in much lesser numbers. Infections are, therefore, highly probable in leukemia patients and chemotherapy causes the situation to worsen. Any fever in those patients should be of paramount importance, and aggressive treatment of infections is crucial to avoid their mortality, either bacterial, viral or fungal.
3) Hyperuricemia:
Uric acid is a product of cellular metabolism, meaning that when a cell dies its DNA breaks into its basic components, which may either be recycled or converted into more basic chemical waste products. One of those components is uric acid. Uric acid is excreted by the kidney and can increase in cancer patients owing to their high rate of cellular destruction or due to chemotherapy acting on the cancer, a condition called tumor lysis syndrome. Allopurinol or rasburicase are drugs commonly used in the treatment of hyperuricemia.
4) Diet:
Diet is an important component in the treatment of leukemia. Patients should eat more fruits and vegetables and make sure that most food is well cooked. It has less to do with the type of food and more to do with the state of their weakened immune system. Such diet is called a neutropenic diet, and ensures the lowest risk of infections via food sources, either bacterial or parasitic.
What if it came back?
Leukemia can come back even after treatment and cause the same problems it caused in the first place. Unfortunately, patients who had a relapse after successful initial therapy have an overall bad outcome and a lower chance of remission through chemotherapy. Many other factors contribute to outcome, including age, severity of the cancer in the first time, and how long did it take to achieve a good response previously.
Options for relapsed cancer include targeted therapy like gemtuzumab ozogamicin. This oddly-named drug showed such a good response in relapsed acute leukemia that it received an accelerated approval, but it can only be used in the presence of a certain genetic anomaly. Other targeted therapy include gilterinib, ivosidenib and enasdenib. Patients who didn’t undergo bone marrow transplantation in consolidation therapy should be considered for one in relapses.
Do I need monitoring after my treatment?
Cancer is not a traditional disease in the sense that it just “goes away” after treatment. It is a defect in your genetic component, you blueprint, and although we can eliminate all trace of it by modern medicine, there is always a risk that it can show itself once more. Therefore, lack of a long-term monitoring after consolidation therapy is a fatal mistake. The current recommended regimen of follow-up indicated a complete blood count every 1-3 months after completion of the consolidation therapy for 2 years, followed by a complete blood count every 3-6 months for another 5 years. A bone marrow aspirate will be needed if any of these tests show an abnormality consistent with a relapse of the disease.