Overview of Acute Myeloid Leukemia

A panel of experts in acute myeloid leukemia provide an overview of the disease state and its clinical features.

KATIE CULOS, PharmD, BCOP : Hello, and welcome to this Pharmacy Times® Practice Pearls: Best Practice for the Management of Acute Myeloid Leukemia. I’m Dr Katie Culos, a hematology/oncology clinical pharmacist at Vanderbilt University Medical Center in Nashville, Tennessee. Joining me today in this discussion is Dr Amanda Brahim, also a hematology/oncology clinical pharmacist at Memorial Cancer Institute in Pembroke Pines, Florida. We also have Dr Yehuda Deutsch, who is a physician practicing in malignant hematology and cellular therapy, also at Memorial Cancer Institute in Pembroke Pines, Florida.

Today, we are going to discuss the best practices in the management of acute myeloid leukemia, which we’ll refer to as AML for the rest of the presentation. We will talk about some distinct patient characteristics that will help us identify appropriate treatment pathways, talk about the challenging decisions from a formulary management perspective, as well as discuss the novel options now for treating in the outpatient setting and how we can optimize patient care.

Let’s get the discussion started with a brief overview of AML. Yehuda, can you start by giving us just a brief overview of AML, focusing on the pathophysiology [and] some different subtypes, as well as potential risk factors?

YEHUDA DEUTSCH, MD: Acute myeloid leukemia, or AML, is the most common form of acute leukemia in adults.

There are about 20,000 new cases or diagnoses of AML each year in the United States, and this has been steadily increasing. The average or median age of patients with AML is 65 years, and as the age increases, this [disease] increases significantly.

AML is the consequence of a malignant transformation of myeloid precursor cells. These leukemic clones produce cells that have increased proliferation and decreased differentiation, meaning that these cells are able to grow and reproduce and are not able to mature into normal, mature blood cells.

Due to this increased clone of malignant cells, the bone marrow is unable to continue its normal function of producing normal, healthy blood cells, such as white blood cells which fight infection, red blood cells which carry oxygen and give energy, and platelets which help decrease the risk of bleeding.

AML is associated with specific chromosomal abnormalities. These include translocations, rearrangements, deletions or gains of parts of chromosome, as well as specific mutations in regulation of cell growth and differentiation. Some of these specific mutations are in pathways that include transcription factors, DNA repair enzymes, epigenetic regulators, regulators of apoptosis, including TP53 [tumor protein], and others.

There are different forms of acute myeloid leukemia. We typically divide this into de novo AML, as well as secondary AML. Secondary AML, being AML that's either therapy related, meaning that it's caused by exposure to chemotherapy or radiation therapy, and AML with myelodysplasia-related changes, which means that it’s an AML that either has transformed from a pre-existing bone marrow disorder, such as myeloid dysplastic syndrome, myeloproliferative neoplasm, or an AML that has very significant amounts of signs of myelodysplasia or cytogenetic changes associated with myelodysplasia. Typically, secondary AML is more difficult to treat. Typically, this is more common in older patients and is sometimes more resistant to standard chemotherapy.