Diagnosis & Treatment of Childhood Acute Myeloid Leukemia

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by preventing their division. When chemotherapy is taken by mouth or injected into a vein, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy).

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or prevent them from growing. In childhood AML, external radiation therapy (radiation given by a machine outside the body that sends radiation toward the cancer) is usually limited to treating chloromas (a type of tumor that can be caused by AML) that does not respond to chemotherapy.

The UH Proton Therapy Center is Cleveland’s first provider of proton therapy, an advanced type of radiation therapy used in the treatment of various cancers. Available only at select hospitals across the country, proton therapy delivers most of its energy to a very narrow field at the location of the cancer, minimizing damage to surrounding healthy tissue. In comparison to other forms of radiation therapy, proton therapy can result in better quality of life during treatment and may reduce the risk of patients developing radiation-induced secondary cancers later in life.

Stem cell transplant is a treatment that replaces the blood-forming cells killed as a result of chemotherapy. Stem cells, which are immature blood cells, are removed from the blood or bone marrow of the patient or a donor, frozen and stored. Following completion of the patient’s chemotherapy, the stored stem cells are thawed and infused into the patient. The reinfused stem cells grow into and restore the body’s blood cells.

Targeted therapy is a form of treatment that uses drugs or other substances to identify and attack specific cancer cells. This therapy generally causes less harm to normal cells than chemotherapy or radiation therapy. The two main types of targeted therapy used in the treatment of childhood AML are:

• Tyrosine kinase inhibitor therapy: Tyrosine kinase inhibitor (TKI) therapy blocks certain chemical messenger enzymes called tyrosine kinases that tumors need to grow. TKIs may be used with chemotherapy drugs as an adjuvant therapy, which is a treatment given after initial treatment to lower the risk of the cancer returning.
  • Imatinib, dasatinib, and nilotinib are types of TKIs used to treat childhood CML
  • Sorafenib and trametinib are types of TKIs being studied in the treatment of childhood AML
• Monoclonal antibody therapy: Monoclonal antibody therapy makes use of antibodies created in a laboratory from a single type of immune system cell. Administered via infusion, monoclonal antibodies attach either to the cancer cells or other cells that may help cancer cells grow, block the growth of the targeted cell, or keep the targeted cells from spreading. For example, gemtuzumab is a type of monoclonal antibody that recognizes a protein called CD33 present in leukemia cells and is used for the treatment of AML.

Another targeted therapy drug is Selinexor, which is being studied in the treatment of refractory or recurrent childhood AML.

Supportive care refers to care measures designed to lessen the complications caused by a disease or its treatment. All patients with childhood AML receive some type of supportive care. Supportive care may include:

• Transfusion therapy: A way of providing red blood cells, white blood cells or platelets to replace blood cells destroyed by disease or cancer treatment. The blood may be donated from another person or taken from the patient earlier and stored until needed.
• Other drug therapies: Other drugs that may be useful in supportive care for childhood AML patients include antibiotics and antifungal agents.
• Leukapheresis: In this procedure, a machine is used to remove white blood cells from the blood. Leukapheresis is used to treat patients with very high white blood cell counts.

Immunotherapy utilizes a person’s own immune system to help kill cancer cells. Most immunotherapeutic approaches are relatively new and in the clinical trial phase of development. These approaches offer hope for young cancer patients to receive effective treatments that may prevent the long-term, damaging side effects associated with more traditional cancer treatment methods such as chemotherapy and radiation.

The physician-scientists at the UH Rainbow’s Center for Pediatric Immunotherapy in the Angie Fowler Adolescent & Young Adult Cancer Institute are spearheading research efforts to find, test and develop immunotherapy agents, which have unlimited potential and may represent the most effective anti-cancer treatment of the future.

Among the promising immunotherapeutic approaches being investigated in the treatment of childhood AML is the use of natural killer (NK) cells, which are cells harvested from the blood of one of the patient’s parents. The harvested cells are given to the patient with the goal of eliminating leukemia cells. When circulating in the bloodstream, NK cells recognize and attach to the AML cell walls, leading to their destruction.

Another form of immunotherapy currently under investigation is the use of chimeric antigen receptor (CAR)-T cells, which are T lymphocytes harvested from the patient’s own blood and genetically engineered in the laboratory in order for them to detect specific markers (antigens) on the cancer cells. These cells are then infused into the patient in order to mount an immune response and kill the leukemia cells. Examples of this type of immunotherapy include CD33 or CD123 CAR-T cells.