Leukemia is a cancer of the white blood cells that grow in bone marrow — the spongy tissue found in the bones. Types of leukemia include acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). One phase of CML, known as the CML blast crisis, can look very similar to AML, but some key differences separate these two conditions.
Both AML and CML involve myeloid cells — hence the conditions’ names. Myeloid cells eventually develop into red blood cells, platelets (involved in clotting), or white blood cells such as neutrophils, eosinophils, and monocytes.
However, AML and CML are classified differently. AML is divided into subtypes based on factors such as the leukemia cells’ appearance under a microscope, genetic mutations (changes), and blood cell counts (red blood cells, white blood cells, and platelets). On the other hand, CML is divided into three different phases of progression — chronic, accelerated, and blast. The blast phase of CML looks similar to AML, and it can be difficult to tell them apart. In fact, CML may not be diagnosed until it progresses from the chronic or accelerated to the blast phase when it is called AML. However, the conditions differ in their behavior and treatment.
AML is a rapidly progressing form of leukemia that begins in the bone marrow and quickly spreads to the blood. It may also go on to affect other areas of the body, including the liver, spleen, and lymph nodes. AML is commonly caused by certain mutations in genes, such as RAS, c-KIT, and FLT3, that prevent bone marrow cells from maturing.
CML is a slowly progressing type of cancer with three phases. Most people are diagnosed in the chronic phase, which can last for many years. However, if it’s not treated, chronic phase CML can progress to the accelerated or blast phase. About two-thirds of blast cases resemble AML, and one-third resemble acute lymphoblastic leukemia (another type of leukemia).
In the accelerated phase, the number of immature white blood cells — known as blasts — rises. An abnormality called the Philadelphia chromosome (Ph chromosome) develops when pieces of chromosomes 9 and 22 break off and switch places in a genetic accident known as a translocation. This results in a smaller-than-normal chromosome 22 with a fusion of two genes (BCR-ABL1). Doctors can see this change on a karyotype, a test that takes pictures of chromosomes to look for changes in their structure or size and can also detect BCR-ABL. The fusion gene produces a protein that signals cells to grow and divide and can’t be turned off. This abnormality defines CML and is present in all three phases — chronic, accelerated, and blast.
During the chronic phase, cells keep growing out of control, eventually leading to accelerated-phase CML. If left untreated, the cancer will progress to the blast phase, which is also known as the blast-crisis phase. In this final phase, blasts begin to build up not only in the blood and bone marrow but also in other tissues and organs. CML blast crisis may produce symptoms of bone and abdominal pain, fever, and loss of appetite.
Although the two types of cancer look similar, the treatments for AML and CML blast crisis differ. This is because CML cells are uniquely sensitive to drugs that target the BCR-ABL mutation. Oncologists (doctors who treat cancer) will use strategies such as targeted therapies and stem cell transplants, as well as chemotherapy and immunotherapy, to treat people with CML blast crisis.
AML is typically treated first with chemotherapy. Examples of these drugs include:
Targeted therapies that zero in on certain gene mutations are also effective in treating AML. These drugs, which are typically used in people who can’t tolerate chemotherapy or are older, include:
The BCR-ABL gene encodes a protein known as a tyrosine kinase. To block this protein’s action, researchers have developed targeted drugs known as tyrosine kinase inhibitors (TKIs). People with CML blast crisis but who haven’t yet been treated may benefit from high doses of the TKI imatinib (Gleevec).
Imatinib is usually successful in earlier phases of CML, allowing people to manage their leukemia for years. However, because the blast phase is more advanced, this TKI may be less effective. People with blast-phase CML may receive newer TKIs such as:
These medications may be more effective if you’ve never taken them before. If other TKIs don’t work well, you may be prescribed ponatinib (Iclusig) or asciminib (Scemblix).
If you are in the CML blast phase, you may receive chemotherapy drugs alone or combined with TKIs, such as:
The only known way to cure blast-crisis CML involves an allogeneic bone marrow transplant, which uses blood cells from a healthy donor. This is done after CML is in remission, meaning the signs and symptoms of cancer are less severe. However, once leukemia has progressed to the blast phase, transplant is often less successful, with a much lower ultimate long-term survival rate: less than 20 percent. Chimeric antigen receptor T-cell therapy, in which the body’s own T cells fight cancer, is also being used more often for CML blast crisis.
Overall, people with AML have a better prognosis (outlook) compared with those with CML blast crisis. The National Cancer Institute estimates that 30 percent of people with AML live for at least five years after a diagnosis. For those with CML blast crisis, the median survival (how long half of people with a disease are still alive after their diagnosis) is seven to 11 months, but this rate appears to be improving with the introduction of new drugs.
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