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.

What Is Plasma Cell Leukemia?

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.

What Causes Plasma Cell Leukemia?

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:

• Older age
• Radiation exposure
• Exposure to certain chemicals, such as asbestos, benzene, pesticides, and herbicides
• Having a blood disorder called monoclonal gammopathy of undetermined significance (MGUS)

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.

Gene Changes That Contribute to 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:

• t(11;14) (chromosomes 11 and 14 are abnormally attached)
• t(14;16)
• t(4;14)
• Deletion of part of chromosome 13
• Extra copies of part of chromosome 1

Knowing these gene changes can help your doctor estimate your prognosis and determine which treatments may be most likely to kill your leukemia cells.

Plasma Cell Leukemia Symptoms

People with PCL have some of the same symptoms as those with multiple myeloma. Symptoms may include:

• Bone pain
• Bone fractures
• Extreme tiredness
• Frequent infections
• Bleeding problems
• Splenomegaly (enlarged spleen)
• Hepatomegaly (enlarged liver)

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:

• Anemia (low levels of red blood cells)
• Thrombocytopenia (low levels of platelets)
• Kidney problems
• Hypercalcemia (high calcium levels in the blood)
• Increased blood levels of lactate dehydrogenase (LDH) or beta-2-microglobulin

Diagnosis of Plasma Cell Leukemia

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:

• More than 20 percent of your nucleated blood cells are abnormal plasma cells.
• You have more than 2 x 10⁹ plasma cells per liter.

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:

• Blood tests to check for signs of organ damage
• Urine tests to look at kidney function
• Bone marrow biopsy (removal of a small sample) to examine blood and leukemia cells
• Imaging tests, such as positron emission tomography-computed tomography (PET-CT) scan, magnetic resonance imaging (MRI), or X-rays of long bones, to look for extramedullary tumors (outside the bone marrow)

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.

Plasma Cell Leukemia Treatments

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.

• In frontline or induction therapy, the first treatments you receive aim to get the leukemia under control by killing as many cancer cells as possible and relieving symptoms.
• Consolidation treatment, which often includes the same drugs as induction therapy, aims to kill any additional cancer cells left behind after the first set of treatments.
• In maintenance therapy, people who receive a stem cell transplant will receive additional medication after the procedure to try to keep cancer from returning and help them live longer.

Chemotherapy

Chemotherapy drugs can block and kill cells that are multiplying. Types of chemotherapy that may be used to treat PCL include:

• Platinol (cisplatin)
• Adriamycin (doxorubicin)
• Velcade (bortezomib)
• Revlimid (lenalidomide)
• Cytoxan (cyclophosphamide)

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 Therapy

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).

Immunotherapy

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).

Stem Cell Transplantation

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

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.

Outlook for Plasma Cell Leukemia

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:

• Older age (at least 60 years old)
• A low platelet count (less than 100 billion/L)
• A high number of plasma cells in the blood (at least 20 billion/L)

Gene changes that are more likely to lead to a poor prognosis include:

• Hypodiploidy (leukemia cells that have too few chromosomes)
• Changes in chromosome 1
• del(17p) (deletion of part of chromosome 17)

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their loved ones. On MyLeukemiaTeam, members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with plasma cell leukemia? Share your experiences in the comments below, or start a conversation by posting on MyLeukemiaTeam.