B-cell prolymphocytic leukemia (B-PLL) is a very rare blood cancer. Experts used to classify B-PLL as a form of chronic lymphocytic leukemia (CLL). Now, however, B-PLL is considered to be a separate type of leukemia. B-PLL may be managed with some of the same treatments used for CLL.

B-PLL makes up fewer than 1 percent of all types of leukemia involving B cells. Men are slightly more likely to get B-PLL than women. This condition occurs most often in older adults. On average, people with B-PLL are diagnosed at the age of 69 years.

What Is B-Cell Prolymphocytic Leukemia?

Normal blood cells form inside of the bones, in tissue known as bone marrow. Leukemia forms when blood cells develop gene changes and grow out of control. When abnormalities appear in these cells, they can grow too quickly, taking over the bone marrow and crowding out healthy cells in the blood.

Leukemia can develop from any type of blood cell. B-PLL develops from B cells, a type of lymphocyte. Lymphocytes are the infection-fighting cells in the immune system.

Some cases of B-PLL develop from chronic lymphocytic leukemia (CLL). Alternatively, some people who are diagnosed with B-PLL have no known history of other types of leukemia. One main difference between B-PLL and CLL is that people with prolymphocytic leukemia have much higher levels of prolymphocytes. B-PLL is also very similar to another rare B-cell cancer called mantle cell lymphoma (MCL). B-PLL cells often have the same gene changes seen in CLL and MCL cells.

Causes of B-PLL

Cancer is thought to develop from multiple gene changes within a cell. However, researchers often don’t know exactly what causes these gene abnormalities. Certain risk factors can increase a person’s chances of developing cancer-causing changes in their genes. For a disease like CLL, which is similar to B-PLL, risk factors include older age, a family history of blood cancer, or exposure to a chemical such as Agent Orange (used during the Vietnam War). However, most people with B-PLL don’t have any known risk factors.

Researchers have begun to identify some of the specific gene changes often found in B-PLL cells, although many of the changes remain unknown. Some gene changes consist of a mutation within one specific gene. Others include abnormalities in a chromosome (a long piece of DNA).

About 50 percent of people with B-PLL have changes in the TP53 gene, and 50 percent have changes in the MYC gene. Some people have abnormalities in both genes, and others don’t have changes in either gene. About 1 out of 4 people with B-PLL have a deletion in part of chromosome 13. These changes may cause cancer cells to divide too quickly.

B-Cell Prolymphocytic Leukemia Symptoms

Many people with B-PLL have a set of symptoms called B symptoms. These symptoms are often seen in people with lymphoma when they are associated with a worse outlook. B symptoms include:

• Fever above 100.4 degrees Fahrenheit (38 degrees Celsius)
• Drenching night sweats
• Weight loss of more than 10 percent of your body mass

B-PLL also frequently leads to very high white blood cell counts, which may continue to increase after diagnosis. Additionally, people with this condition often have anemia (low levels of red blood cells) and thrombocytopenia (low levels of platelets). B-PLL also causes splenomegaly (enlarged spleen). If you have splenomegaly, you may notice pain in the upper left part of your abdomen, and you may feel full after only eating a little.

Diagnosis of B-PLL

Leukemia diagnosis often starts with blood tests. Many people undergo a complete blood count (CBC) test, which measures the levels of each type of blood cell within a blood sample. Another possible blood test is a peripheral blood smear, in which a doctor looks at blood cells under a microscope. If a doctor suspects leukemia, they may also recommend a bone marrow biopsy or aspiration (procedures to collect samples of bone marrow cells). People with B-PLL have very high levels of prolymphocytes. You need to have at least 55 percent prolymphocytes in your blood or bone marrow to be diagnosed with PLL.

When diagnosing B-PLL, doctors have to rule out other similar types of blood cancer. For example, B-PLL can look very similar to T-cell prolymphocytic leukemia (T-PLL). The difference between these two conditions is whether leukemia developed from a B cell or a T cell. These two cell types contain different proteins on their outer surfaces. The proteins can be “read” using a test called immunophenotyping or flow cytometry. Immunophenotyping is often used to confirm B-PLL. It helps distinguish between B-PLL and other similar types of blood cancer, such as:

• T-PLL
• CLL
• MCL
• Hairy cell leukemia
• Splenic marginal zone lymphoma

Doctors may also use blood and bone marrow samples for cytogenetic tests, such as karyotyping or fluorescence in situ hybridization (FISH). Cytogenetic tests help doctors find changes in genes or chromosomes. Knowing which gene changes are present within leukemia cells helps doctors estimate prognosis and recommend treatments that are more likely to be effective.

B-Cell Prolymphocytic Leukemia Treatments

Because B-PLL is so rare, doctors have not yet been able to figure out the best treatment plans. Participating in clinical trials may be a good option for people with B-PLL. During a clinical trial, participants may be able to receive new treatments that work better than previous treatments. Alternatively, participants may be given previously approved drugs in new combinations or at new doses.

Watch and Wait

If you don’t have symptoms when you are diagnosed, you may not need treatment right away. Waiting to start treatment means that you can delay some of the side effects of cancer therapies. However, B-PLL can grow quickly, so you will need to have frequent follow-up doctor’s visits while you are waiting. These visits help your health care team know when the leukemia is getting worse. About 10 percent to 15 percent of people with B-PLL don’t have symptoms right away and may be able to use a watch-and-wait approach.

Medications for B-PLL

B-cell prolymphocytic leukemia can be treated with both chemotherapy and targeted therapy medications. Chemotherapies are medications that kill quickly growing cells. They can kill cancer cells, but also frequently kill your body’s normal, healthy cells, too. On the other hand, targeted therapies recognize specific proteins found only on cancer cells. They target these proteins to stop cancer cells from growing and kill the cells. Targeted therapies don’t usually affect normal cells as much as chemotherapies do.

Most people with B-PLL receive a combination of chemotherapy and targeted therapy. The targeted therapy drug often used to treat this leukemia is Rituxan (rituximab). Rituximab attaches to a protein called CD20 found on B cells. Treatment plans combining rituximab and chemotherapy drugs may include:

• FCR — Fludara (fludarabine), Cytoxan (cyclophosphamide), Rituxan (rituximab)
• BR — Treanda (bendamustine) and rituximab

Chemotherapy drugs often do not work well for people who have a mutation in the TP53 gene. In this case, people may be able to receive other targeted therapies. These medications have not been specifically approved to treat B-PLL, but they are approved for other types of leukemia that develop from B cells. These targeted therapies include:

• Imbruvica (ibrutinib)
• Zydelig (idelalisib)
• Venclexta (venetoclax)

If B-PLL is relapsed (came back after being treated) or refractory (resistant to treatment), doctors may recommend other treatment options.

Stem Cell Transplant

Chemotherapy often damages healthy blood cells. Using high doses of chemotherapy drugs kills more cancer cells but also causes more severe side effects. During a stem cell transplant, a person with B-PLL undergoes aggressive chemotherapy and then receives new blood stem cells from a donor. The stem cells make new, healthy blood cells to replace the ones that were damaged by chemotherapy.

Stem cell transplantation is the only treatment that has the possibility of curing B-PLL. However, this procedure is risky. It is usually only an option for younger people who have no other health problems and went into remission after being treated with medication.

B-PLL Outlook

B-cell prolymphocytic leukemia is often an aggressive disease. It can progress quickly. People with B-PLL often live for an average of three years after being diagnosed.

Some people have prognostic factors that make them more or less likely to have a good outcome. Deletions of part of chromosome 17 or mutations in the TP53 gene often lead to a poor prognosis. This is because people with these gene changes often have leukemia that is resistant to chemotherapy. Additionally, having a very high lymphocyte count can increase a person’s risk of a worse outcome.

Talk With Others Who Understand

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