Plasma cell leukemia (PCL) is a rare blood cancer. It is related to multiple myeloma (MM). About 1,200 people are diagnosed with PCL each year in the United States, which makes up about 0.6 percent of all MM cases. PCL is slightly more likely to affect men than women and may occur more often in Black people than in white people. Plasma cell leukemia is an aggressive disease, and those who are diagnosed with the condition should start treatment right away.
PCL develops from plasma cells, a type of white blood cell that plays an important role in the immune system. When the body encounters germs like viruses or bacteria, plasma cells make antibodies to fight them off. When plasma cells become cancerous, they can develop into different kinds of malignancies, such as multiple myeloma or PCL.
Some cases of PCL occur in people who have never had any other type of blood cancer. These are called primary PCL. More often, PCL develops in people who have multiple myeloma. Doctors call these cases secondary PCL. About 1 percent to 4 percent of individuals with MM develop secondary PCL.
In people with multiple myeloma, cancerous plasma cells form in the bone marrow and generally stay there, although they can also form colonies in the spleen, bones, and less commonly, in other organs. In PCL, the leukemic plasma cells fill up the bone marrow and spill out into the bloodstream. Experts view PCL as a more advanced form of myeloma.
Leukemia develops when a blood cell undergoes genetic changes. The changes cause the abnormal cell to start growing and dividing. Eventually, the abnormal cells take over, crowding out the body’s normal, healthy blood cells.
Certain risk factors can make a person more likely to develop cancerous gene changes. Experts don’t yet fully understand which risk factors can lead to PCL. So far, research shows that PCL risk factors are probably similar to MM risk factors. Multiple myeloma risk factors include:
People with multiple myeloma have a greater risk of developing PCL. New treatments are helping those with MM live longer, which means that more people have a chance of developing PCL.
People with PCL often have mutations in certain genes. Many of these genes control cell growth or cell death. Genes that may be mutated in PCL cells include TP53, DIS3, NRAS, KRAS, and BRAF.
PCL cells also often contain chromosomal changes. Chromosomes are the long pieces of DNA that contain all of a cell’s genes. About 50 percent of people with PCL have a deletion in part of chromosome 17. Other chromosome changes include:
Knowing these gene changes can help your doctor estimate your prognosis and determine which treatments may be most likely to kill your leukemia cells.
People with PCL have some of the same symptoms as those with multiple myeloma. Symptoms may include:
Laboratory tests can also show other signs of PCL. These signs may be uncovered during diagnostic tests for leukemia or during routine tests performed as part of a physical exam. Signs of PCL include:
Because PCL causes cancerous cells to enter the bloodstream, a blood test can identify leukemia cells. In order to be diagnosed with PCL, one of the following statements must apply:
Having one of the above characteristics is enough to be diagnosed with PCL, according to the World Health Organization and the International Myeloma Working Group. However, some doctors will also diagnose PCL if a person has at least 5 percent plasma cells in the blood.
The tests used to diagnose PCL are similar to those used to diagnose MM. Different kinds of blood tests may be needed to determine whether cancer cells are in the blood. Your doctor may collect blood for a peripheral blood smear, which looks at the morphology (size and shape) of blood cells. Another blood test is a complete blood count (CBC), which measures the levels of different types of blood cells. You may also need to undergo:
Samples from your blood or bone marrow may also be sent to a laboratory to undergo further testing. One lab test used to diagnose PCL is flow cytometry. This test reads a cell’s immunophenotype (markers or proteins found on the surface of a cell). PCL cells tend to have slightly different proteins on their surface when compared with MM cells, so flow cytometry can help distinguish between PCL, MM, and other blood cancers.
Lab tests may also include cytogenetic tests, which can show chromosome abnormalities or gene mutations.
People with PCL are treated with some of the same therapies that doctors use to treat MM. However, the treatment regimens may be more aggressive because PCL is a more severe, faster-growing cancer. Additionally, people who previously had multiple myeloma before developing PCL have usually already gone through treatment. Their leukemia cells might be refractory (resistant) to these myeloma treatments. People with refractory PCL may need to switch to other therapies.
Plasma cell leukemia treatments are often given in three phases. Each of these phases has a different goal.
Chemotherapy drugs can block and kill cells that are multiplying. Types of chemotherapy that may be used to treat PCL include:
Chemotherapy may be combined with targeted therapies, a stem cell transplant, or steroids such as Deltasone (prednisone) or Decadron (dexamethasone). In recent years, many new drugs that can be helpful to treat PCL are being studied and released.
Targeted therapies are used to kill cancer cells while leaving the body’s normal cells alone. Targeted therapy drugs recognize specific genes or proteins found on cancer cells.
Researchers have developed many targeted therapies that can help treat MM. Some of these may also be used to treat PCL. In particular, many doctors use Velcade (bortezomib) to treat PCL. Bortezomib is a type of targeted therapy called a proteasome inhibitor. It blocks enzymes called proteasomes, which are responsible for removing old or unneeded proteins found in cells. Plasma cells make a lot of proteins. Bortezomib stops them from getting rid of the excess proteins, making the plasma cells more likely to die.
If someone has PCL that is resistant to other targeted therapies, they may be able to use a different proteasome inhibitor called Kyprolis (carfilzomib). New drugs are being constantly added to the armamentarium for MM and PCL. The most recently approved drugs are Xpovio (selinexor) and Sarclisa (isatuximab-irfc).
Immunotherapies boost the immune system, helping it better fight cancer cells. Immunotherapy medications used to treat PCL include Revlimid (lenalidomide), and less commonly, Thalomid (thalidomide). If someone’s PCL cells grow resistant to these drugs, their doctor may prescribe another immunotherapy, called Imnovid (pomalidomide).
A stem cell transplant is a procedure in which a person receives new blood stem cells (cells that form all of the other types of blood cells). Before undergoing this procedure, a person is given high-dose chemotherapy called Alkeran (melphalan) to kill off leukemia cells. The chemotherapy also damages normal blood cells. Then, stem cell transplantation provides a new source of healthy blood cells.
There are two types of stem cell transplantation. In each type, the stem cells come from a different source. For allogeneic transplants, a healthy donor provides blood stem cells. For autologous transplants, a person’s stem cells are taken out before chemotherapy and are then put back once the treatment is done.
Both allogeneic and autologous stem cell transplants may be used to help people with PCL live longer. However, some studies have shown that autologous stem cell transplantation may lead to better outcomes.
Chimeric antigen receptor (CAR) T-cell therapy is another promising treatment for myeloma and PCL that is coming into wider use.
Clinical trials are underway to find better treatments for people with PCL. Clinical trials can help researchers discover whether new medications, new drug combinations, or new drug dosages are safe and effective. They also help people with leukemia access new treatment options that wouldn’t otherwise be available. Ask your doctor for more information about which clinical trials may be an option for you.
Previous studies show that people with PCL live for an average of one year after being diagnosed. However, this statistic was calculated using data from over a decade ago. Newer treatments for PCL have been improving survival rates, and the average survival of people diagnosed with PCL today may be better. For example, people who receive a stem cell transplant may live for an average of two to three years.
People with PCL who first had multiple myeloma have a poor prognosis (outlook). Those who have been diagnosed with primary plasma cell leukemia are more likely to have a better outcome.
People with the following characteristics also tend to have poor outcomes:
Gene changes that are more likely to lead to a poor prognosis include:
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