Acute Myeloid Leukemia

Overview

AML begins in early myeloid cells, which normally mature to become white blood cells (with the exception of lymphocytes), red blood cells or platelets. Instead of developing into these normal blood elements, they multiply rapidly, creating an excess of abnormal myeloid cells that crowd out healthy blood-forming cells in the bone marrow. The few healthy blood-forming cells cannot keep up, resulting in low numbers of healthy white blood cells, red blood cells and platelets. This increases the risk for infection, anemia and excessive bruising and/or bleeding issues.

Classifying AML

Your doctor may recommend blood tests, bone marrow aspiration and biopsy, a lumbar puncture and imaging tests to determine the specific subtype of leukemia. A pathologist looks at how developed the leukemia cells are and how different they look from normal cells.


Next, genetic and molecular testing should be performed to look for genetic mutations, or alterations, in the genes within the leukemic cells. Specialized tests, such as flow cytometry, fluorescence in situ hybridization (FISH) and reverse transcriptions-polymerase chain reaction (RT-PCR), will likely be used to identify subtypes of AML, proteins, chromosomes, genes and other factors involved in leukemia. Next-generation sequencing may be ordered.


Certain genetic mutations are associated with a better prognosis than others. Some mutations respond better to certain types and dosages of drug therapy. Still others may influence the timing or need for a stem cell transplant. Some targeted therapies are approved to treat certain AML genetic mutations, such as FLT3 (pronounced "flit-three"), IDH1 and IDH2. Not all genetic mutations are always present during diagnostic testing, so your doctor will likely retest if the disease relapses (returns) to determine treatment.


Your doctor uses the test results to determine your outlook for recovery (prognosis) by categorizing the disease as low risk, intermediate risk or high risk. This risk is related to how quickly the leukemia cells may grow and the likelihood the leukemia will come back in the future, and if so, the potential long-term prognosis. 


Your AML is then classified. The subtype of AML and whether it has spread outside the blood and bone marrow to to other parts of the body are used to plan treatment. The World Health Organization (WHO) classifies AML into subtypes based on the appearance of the leukemia cells, as well as the presence or absence of certain chromosomal changes and/or genetic mutations in the leukemia cells (see Table 1).

Table 1 - WHO Classification System
AML with recurrent genetic abnormalities
Subtypes:
  • AML with a translocation between chromosomes 8 and 21
  • AML with a translocation or inversion in chromosome 16
  • AML with a translocation between chromosomes 9 and 11
  • APL (M3 subtype) with a translocation between chromosomes 15 and 17
  • AML with a translocation between chromosomes 6 and 9
  • AML with a translocation or inversion in chromosomes 3
  • AML (megakaryoblastic) with a translocation between chromosomes 1 and 21
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML not otherwise specificed (includes cases that do not fall into any other group; similar to the FAB classification system)
Subtypes:
  • AML with minimal differentiation (M0)
  • AML without maturation (M1)
  • AML with maturation (M2)
  • Acute myelomonocytic leukemia (M4)
  • Acute monoblastic/monocytic leukemia (M5)
  • Pure erythroid leukemia (M6)
  • Acute megakaryoblastic leukemia (M7)
  • Acute basophilic leukemia
  • Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Undifferentiated or biphenotypic acute leukemias (leukemias that have both lymphocytic and myeloid features; also called ALL with myeloid markers, AML with lymphoid markers, or mixed lineage leukemia)
Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.

Treating AML

Your treatment plan involves many factors, including your AML subtype, diagnostic, genetic, and molecular test results, age, other medical problems you might have and your preferences for quality of life.


Treatment generally consists of two phases: remission induction therapy and post-remission therapy. During remission induction therapy, the goal is to destroy the leukemia cells in the blood and bone marrow, putting the AML into complete remission. Complete remission is defined as having blood counts that are back to normal, the elimination of leukemia cells in blood samples that are examined under a microscope, and no signs or symptoms of the disease. The goal of post-remission therapy, also called consolidation therapy, is to kill any remaining leukemia cells that could cause a relapse.


The following options may be used alone or in combination.


Chemotherapy kills cancer cells with some healthy cells, throughout the body. Chemotherapy may be used alone or followed by stem cell transplantation. The choice of chemotherapy drug depends on several factors, including your age (whether you are younger or older than 75), risk factors and prognosis (predicted outcome after treatment). The use of high-dose chemotherapy typically requires a lengthy hospital stay so the patient's blood counts can be closely managed. When AML has spread to the brain and spinal cord, chemotherapy may be injected into the fluid-filled space between the thin layers of tissue that cover the brain and the spinal cord (intrathecal chemotherapy).


Stem cell transplantation may be used depending on the AML subtype and whether the AML is refractory. AN allogeneic transplant is most commonly used for AML. That involved donated stem cells. Other less-matched donor options are under investigation and in clinical trials now to provide access for patients who have no available matched donor. 


An allogeneic transplant can work directory against the cancer through the graft-versus-tumor effect (also called graft-versus-leukemia or graft-versus-cancer-cell). This may occur when the donor's white blood cells (the graft) attack any cancer cells (the tumor) remaining after high-dose conditioning treatments, and the effect can be the key to a successful outcome.


You will benefit from the help of a caregiver post-transplant. Among other things, a caregiver will help recognize and manage the potential short- and long-term effects of a transplant. Ask your doctor what to watch for and how long you may need assistance.


Targeted therapy uses drugs or other substances to identify and attack specific cancer cells. Targets include gene mutations, alterations and proteins. Targeted therapy is intended to affect only cancer cells.


It may  be given alone or in combination with chemotherapy, depending on the presence of certain gene mutations (alterations) or specific proteins on the surface of the leukemia cells. Some AML genetic mutations treated with targeted therapy include FLT3, IDH1 and IDH2.


Radiation therapy is the use of high-energy radiation to destroy cancer cells. It is rarely used to treat AML, but may be used if the cancer has spread to the brain, spinal fluid or testicles. It may also be used to shrink a collection of leukemia cells that has formed a mass somewhere. Some people with localized disease or bone pain that does not lessen with chemotherapy may receive radiation therapy to specific parts of the body. It may also be given to the entire body (total body radiation) before stem cell transplantation.


Leukapheresis is not a treatment for AML but may be used to treat leukostasis, which occurs when a very high number of leukemia cells are present in the blood. This condition can cause problems with normal blood circulation. During leukapheresis, blood is removed to collect specific blood cells and then the remaining blood is returned to the body. It is used to lower white blood cell counts immediately but only works temporarily.


Growth factors are sometimes given during post-remission chemotherapy to increase the number of white blood cells that are available to fight infection. Normally, the number of white blood cells is decreased by the chemotherapy and growth factors can help the number to increase back to normal faster. Also, growth factors may be given to collect stem cells before a bone marrow transplant.

Drug therapies for AML

These therapies may be used alone or in combination.
azacitidine (Onureg)
cytarabine (Ara-C)
daunorubicin
daunorubicin/cytarabine liposomal (Vyxeos)
doxorubicin hydrochloride (Adriamycin)
enasidenib (Idhifa)
gemtuzumab ozogamicin (Mylotarg)
gilteritinib (Xospata)
glasdegib (Daurismo)
idarubicin (Idamycin, Idamycin PFS)
ivosidenib (Tibsovo)
midostaurin (Rydapt)
venetoclax (Venclexta)

As of 10/13/21

Relapsed and refractory AML

When AML returns, it is called relapses AML. AML that is resistance at the beginning of treatment or that becomes resistant after being treated for a length of time is called refractory AML. Drug therapy, an allogeneic stem cell transplant or a clinical trial may be available treatment options.

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