Mixed-phenotype acute leukemia (MPAL) is a rare type of blood cancer. Typically, a doctor can classify the cancer as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), depending on the cells involved. However, MPAL presents with features of both AML and ALL.

Leukemia describes a cancer of the blood or bone marrow. There are many types of leukemia, and doctors typically classify them as either acute (sudden) or chronic (slow), depending on how quickly the cancer develops. They can then further classify these cancers depending on whether they affect myeloid or lymphocytic blood cells.

MPAL refers to a rare subtype of leukemia that displays no clear sign of origin and presents with features of both AML and ALL.

In this article, we will discuss MPAL leukemia, including the symptoms, diagnosis, treatment options, and outlook.

Mixed-phenotype acute leukemia (MPAL) is a rare type of acute leukemia where leukemia cells present with both myeloid and lymphocytic features. Some may also refer to this type of leukemia as acute leukemia of ambiguous lineage (ALAL), mixed-lineage leukemia, and acute undifferentiated leukemia.

In 2008, the World Health Organization (WHO) introduced the term MPAL to classify this group of blood cancers. Previously, the scientific community used other terms such as biphenotype acute leukemia to label these diseases.

A doctor may also further classify MPAL into bilineal or biphenotypic leukemia. The former refers to two separate populations of cells with myeloid and lymphoid origin, while the latter describes a single population of leukemia cells that express markers of both lymphoid and myeloid origin.

Some evidence suggests that the frequency of MPAL is 3%, while other research indicates that it accounts for roughly 25% of all acute leukemia diagnoses. MPAL can affect both children and adults.

As with other types of acute leukemia, the exact cause of MPAL is currently unknown. Some evidence suggests that MPAL may derive from alterations in blood stem cells that have the ability to undergo myeloid and lymphoid differentiation.

Research indicates that genetic alterations are associated with acute leukemias and may explain the abnormal development and maturation of white blood cells.

Certain genomic alterations may drive the biphenotypic expression in leukemia cells. Chromosome alterations that are often present in individuals with MPAL include Philadelphia chromosome and chromosome 11q23 abnormalities.

Potential risk factors for developing leukemia may include:

The symptoms of MPAL can occur suddenly and typically relate to problems with bone marrow. Symptoms can include:

Many of these symptoms are common to other conditions, including other types of leukemia. However, healthcare practitioners are aware of symptoms that may indicate MPAL leukemia and will request further testing if they think it is necessary.

Initially, doctors will likely use the same tools for diagnosing other forms of leukemia. These may include:

Due to the lack of consensus on the diagnostic criteria for MPAL, it can be difficult to diagnose the condition. The WHO diagnostic criteria provide a small list of specific lineage markers that can help diagnose MPAL.

Health experts use an immunophenotyping method, known as flow cytometry, on blood or bone marrow samples to identify these markers on leukemia cells.

This technique uses light to detect and measure the characteristics of cells. For an MPAL diagnosis, the sample will contain markers of both myeloid and lymphoid origin. This can also help guide if an AML or ALL treatment regimen will be more appropriate for a treatment plan.

If a doctor suspects an MPAL diagnosis, they will likely request genetic testing to identify the presence of genetic alterations, such as Philadelphia chromosome and chromosome 11q23 abnormalities. This is because a person with these alterations may require a more intensive treatment plan.

Treatment options for MPAL leukemia will vary depending on the diagnosis, age, and medical history. As MPAL leukemia is challenging to treat, the treatment plan is often intensive and usually starts quickly after diagnosis.

A 2018 systematic review and meta-analysis and a 2017 review both suggest that using a chemotherapy regimen for ALL or a combined ALL/AML regimen can result in a better outcome for people with MPAL leukemia than using chemotherapy that doctors use only for AML. A 2019 paper also suggests that ALL treatment may be preferable for treating MPAL.

A 2020 study notes that in cases of MPAL with a Philadelphia chromosome abnormality, the use of targeted therapy such as tyrosine kinase inhibitors can help to improve outcomes.

Doctors may consider other treatments if these options do not provide a satisfactory response. For example, they may use immunotherapies, which activate the immune system to detect and attack cancer cells. A doctor may also perform a stem cell transplant to eradicate any remaining leukemia cells in the bone marrow.

Historically, the outlook for individuals with MPAL has not been very positive. However, with more research and advances in treatment options, the outlook is improving. While it remains hard to predict the overall survival for those with MPAL, evidence suggests that factors that may predict a less positive outcome include:

A 2017 retrospective study suggested the three-year overall survival rate for MPAL was 56.3%, compared with the 5-year survival rate of 65% for leukemia in general. Like other acute leukemias, the quicker the diagnosis and treatment of MPAL, the higher the chance of recovery.

MPAL is a rare form of blood cancer that presents with clinical features of AML and ALL. As with other acute leukemias, the exact cause is unknown, but many cases are associated with genetic abnormalities. Due to its rarity and various diagnostic criteria, it can be a difficult condition to diagnose.

Treatment options vary depending on an individuals diagnosis, age, and medical history but may include chemotherapy, targeted therapy, immunotherapy, and stem cell transplants. While the outlook for MPAL is generally poorer than other leukemias, advances in research and treatments are improving outcomes.

Excerpt from:
MPAL leukemia: Symptoms, diagnosis, and treatments - Medical News Today