Biphenotypic leukemia is a mixed type of leukemia that originates in both lymphoid and myeloid cells. It typically has a poorer outlook than other acute leukemias. A stem cell transplant may improve your outlook but also has serious risks.

Biphenotypic acute leukemia (BAL) is an uncommon type of leukemia. Leukemia is cancer of the blood cells. BAL gets its name because it has features of two different types of leukemias. Biphenotypic means both types.

Most acute leukemias are classified as either myeloid or lymphoid:

  • Lymphoid cells give rise to cells called lymphocytes. These are the white blood cells that help your body fight infections.
  • Myeloid cells give rise to other types of white blood cells called granulocytes and monocytes.

If the origin of the leukemia is myeloid, it’s called acute myeloid leukemia (AML). If the origin of the leukemia is lymphoid, it’s called acute lymphoblastic leukemia (ALL). Acute means that the cancer grows quickly and needs treatment right away.

In rare cases, acute leukemia expresses both lymphoid and myeloid origin. BAL is a mixture of AML and ALL.

In 2008, the World Health Organization (WHO) revised its classification system for leukemia and introduced a new term called mixed-phenotype acute leukemia (MPAL), which includes BAL.

BAL is more difficult to treat than other types of leukemia due to its mixed qualities. The outlook is usually poor compared with AML or ALL.

Leukemia happens when stem cells in your blood undergo genetic changes that make them grow out of control. Like other types of leukemias, the cause of BAL is likely a combination of genetic and environmental factors, but the exact cause isn’t completely understood.

BAL can occur at any age but is more common in adults over age 60. BAL is slightly more common in people assigned male at birth. The incidence is similar across races and ethnicities.

How common is biphenotypic acute leukemia?

BAL isn’t common. According to 2023 data from the American Cancer Society, leukemia (all kinds) makes up just 3% to 4% of cancer diagnoses. Only 1% to 5% of all acute leukemias are BAL. Scientists estimate there are just 0.35 cases per 1 million people per year.

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A diagnosis of BAL can be challenging because this type of cancer is so uncommon. Your doctor will start by taking your medical history and doing a physical exam. Based on your symptoms and history, your doctor may order lab tests to check for any abnormalities in your blood. These tests may include:

If the results of these tests suggest you might have leukemia, your doctor will order a bone marrow aspiration. The procedure involves taking a small sample of the liquid part of the tissue inside your bones.

Your doctor may also perform a bone marrow biopsy at the same time. A biopsy involves removing a sample of bone marrow. Doctors can use the collected samples to characterize your leukemia cells further.

If a doctor confirms a leukemia diagnosis, you’ll need more tests to understand the type of leukemia you have. This may involve:

  • analysis of a bone marrow or blood sample to find out the antigen markers on the leukemia cells using a method known as flow cytometry
  • genetic testing

Is biphenotypic leukemia more serious?

BAL is considered more serious than other types of acute leukemias because it is often more difficult to diagnose and treat. The leukemia cells in BAL have traits of both myeloid and lymphoid cells. They may not respond as well to chemotherapy meant to target one specific type of leukemia cell.

A stem cell transplant can provide a cure for some individuals. But many people with BAL experience a relapse.

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Not all doctors agree on the best way to treat BAL. Since BAL is so rare, there are no clear treatment guidelines. Several studies suggest that ALL treatment is more effective than AML treatment in cases of BAL.

Experts recommend treating BAL with chemotherapy followed by an allogeneic stem cell transplant (SCT), also called a bone marrow transplant. “Allogeneic” means you receive blood cells from a donor’s blood or bone marrow. These cells grow into healthy blood cells to replace the ones you lost during chemotherapy.

SCT also carries a high risk of serious side effects, including graft-versus-host disease (GvHD) and infections. GvHD is a reaction against the donor cells. There’s also a chance the cancer will return after treatment.

Your doctor may also recommend adding a type of targeted therapy called a tyrosine kinase inhibitor (TKI) to the chemotherapy if your cancer cells display specific genetic changes.

Your outlook will depend on many factors, including:

  • your age
  • your overall health
  • your initial white blood cell (WBC) count
  • the type of gene or chromosome abnormality present in your cells
  • how well you respond to the initial chemotherapy

People who go into complete remission within about a month after starting treatment tend to have a better outcome than those who take longer to enter remission.

A 2017 retrospective study estimated the 3-year survival rate for BAL at about 56% in people who underwent a stem cell transplant between 2000 and 2014. That means that slightly more than half of the people with BAL were alive 3 years after diagnosis.

Children have a better outlook than adults. In one retrospective study, the 5-year survival rate for children with BAL was about 77%. This is compared with a 5-year survival rate of 90% for children with ALL and 65% to 70% for children with AML.

BAL is a mixture of ALL and AML. The mixed type makes it more difficult to diagnose and treat than other types of acute leukemia. Treatment typically involves chemotherapy and potentially a stem cell transplant.

Though the outlook is usually poor, survival rates for all types of leukemia have gotten better over time as diagnostic and treatment methods have improved over the last few decades.

Some people with BAL may achieve long-term remission and may even be cured. If you have BAL, consider reaching out to the Leukemia & Lymphoma Society for educational and financial resources and support, including advice on joining a clinical trial.