Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the rapid uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children, with the average age at diagnosis being more than 65 years. However, diagnostic procedures and treatment of children and adults are similar.
In order to understand the best treatment options available for AML, patients should know the classification or histologic subtype of the cancer and the results of analyses of chromosomes determined by cytogenetic examination. These are tests performed on a sample of the patient’s bone marrow. AML is frequently associated with abnormal chromosomes of the leukemia cells. Knowing the specific chromosomal abnormalities associated with leukemia is important for determining specific treatments and outcomes.
Cytogenetics in Adult AML
The following table reports the outcomes of treatment according to whether favorable or unfavorable cytogenetics were present in patients with AML treated with standard intensive chemotherapy. The table illustrates the importance of cytogenetic analyses in adults.
|Favorable: t(8, 22), t(15,17) and inverted 16||60-80%|
|Intermediate: normal karyotypes||40%|
|Unfavorable: all other clonal cytogenetic abnormalities||20%|
Cytogenetics in Childhood AML
Changes in chromosomes in leukemia cells can be identified in 80% of children with AML. These distinct chromosomal changes detected on cytogenetic examination are often associated with different outcomes of treatment. With current treatment, 30-50% of children with AML are cured. It is important to identify those children who can be cured with standard treatments and those who should receive more individualized treatment. The distinct type of chromosomal abnormality present at diagnosis has been shown to help identify patients with a “good” or “bad” outcome.
In one Pediatric Oncology Group study, outcomes of 478 children with AML were reported. They found that children with an inverted 16th chromosome had a survival rate without relapse of 58%, those with a translocation of chromosomes 8 and 21 had a survival rate without relapse of 45% and patients with no chromosomal abnormalities had a survival rate without relapse of 45%. Children with translocation of chromosomes 15 and 17 had a survival rate without relapse of 20% and children with 11q23 abnormalities had a survival rate of 24%.
This study shows that children with AML who have “bad” chromosomal changes should not be treated with standard chemotherapy, but instead should be entered into clinical trials evaluating new therapies or be treated with a stem cell transplant.
Molecular Monitoring of Minimal Residual Disease
Patients with leukemia containing cytogenetic abnormalities can often be tested after treatment for the detection of small numbers of leukemia cells that cannot be detected under the microscope. The technique used is called polymerase chain reaction (PCR). PCR can detect very small numbers of leukemia cells, thereby indicating the need for more treatment, as small numbers of leukemia cells inevitably lead to a relapse. PCR is useful for the monitoring of treatment results of both children and adults with AML.
The treatment of AML occurs in 2 phases. All histologic subtypes are currently treated the same way except for acute promyelocytic leukemia (M3 subtype).
The initial treatment phase of AML is called remission induction and the goal of remission induction therapy is to achieve a complete remission or disappearance of all detectable leukemia cells. After a complete remission is achieved, the second phase of treatment, post-remission therapy, begins. Post-remission therapy is necessary because, although there may be no detectable cancer cells after remission induction, undetectable leukemia cells still exist and the leukemia will return without additional post-remission therapy. Post-remission therapy is often referred to as consolidation.
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