T-cell prolymphocytic leukemia (T-PLL) is a rare cancer that makes up about 2 percent of all chronic leukemias in adults. T-PLL affects mature T cells, which play important roles in the immune system. In 2017, the World Health Organization classified T-PLL as an aggressive form of T-cell leukemia. Though there are treatment options that lead to complete remission for many people living with T-PLL, relapse is common. Doctors and researchers are still working to find a cure.

What Causes T-Cell Prolymphocytic Leukemia?

All cancers are the result of genetic changes. Chromosomes are long pieces of DNA that contain our genetic code. T-PLL often occurs when chromosome number 14 gets rearranged. This rearrangement affects the T-cell receptor, leading to the overexpression of a gene that causes the cell to become cancerous (called a proto-oncogene). This change permanently turns on the cell growth cycle, even when the cell is lacking the “go” signal or receiving the “stop” signal.

Another abnormality common in T-PLL is the deletion of a gene that provides the “stop” signal for cell growth and division. This gene is important for the suppression of cancerous cells. Once cells are stuck in a constantly moving cycle of proliferation, they don’t respond correctly to signals, supplies of nutrients, or DNA damage. A buildup of damaged cells that keep creating more of themselves leads to cancer.

Signs and Symptoms of T-Cell Prolymphocytic Leukemia

T-PLL affects the blood, lymph nodes, spleen, liver, skin, central nervous system, and bone marrow. It usually begins with rapidly increasing numbers of white blood cells leading to abnormally high levels. Other signs can include:

• Anemia — A lack of red blood cells, leading to fatigue
• Effusions — Fluid buildup in the skin, lungs, or abdomen
• Hepatomegaly — An enlarged liver
• Lymphadenopathy — General disease of the lymph nodes
• Splenomegaly — An enlarged spleen
• Thrombocytopenia — A deficiency of platelets in the blood, leading to bruising and slow blood clotting

Other symptoms of T-PLL include:

• Unintentional weight loss
• Night sweats
• Fever

Diagnosis of T-Cell Prolymphocytic Leukemia

Guidelines for diagnosis and treatment of T-PLL were set by the T-PLL International Study Group.

Several tests are required to correctly diagnose T-PLL.

• A detailed personal and family medical history, along with a physical exam, are usually the first steps in diagnosis.
• A blood count and differential count are used to determine the number of lymphocytes (white blood cells) in the blood. This number is very high in people living with T-PLL.
• A blood smear is used to look at cancer cell morphology (size and shape).
• Genetic testing of cancer cells is used to find genetic mutations.
• To help with diagnosis, the immunophenotype (or functionality) of T cells may be tested with flow cytometry. T-cell receptor rearrangement testing using the polymerase chain-reaction method can provide a secure diagnosis in many cases.

After diagnosis, an evaluation of the bone marrow is done to determine the best treatment.

Read more about these diagnostic tests here.

Treatment of T-Cell Prolymphocytic Leukemia

Most people living with T-PLL have an aggressive disease course. However, 20 percent to 30 percent of people living with the condition have a stable or slowly progressing disease without symptoms, which may be called inactive disease. These two groups are treated differently.

Those with active disease are put on a treatment regimen as soon as possible, and those with inactive disease are typically monitored carefully in a watch and wait approach. That’s because studies have shown no benefit to immediately treating people living with inactive T-PLL. Most cases of inactive disease progress to active disease within two years, at which point treatment becomes necessary.

T-PLL progresses quickly, which makes executing long-term studies of different oncology (cancer) treatments difficult. Though therapy cannot cure T-PLL, it can help relieve symptoms and improve the overall survival of people living with T-PLL.

Alemtuzumab

First instances and relapses of T-PLL are usually treated with Campath (alemtuzumab). Campath is a monoclonal antibody (a human-made antibody that can help the immune system). It can kill cancerous T cells, leading to complete remission in around 90 percent of people living with T-PLL. However, it is not a cure — relapse is common.

Campath is typically given intravenously (into a vein) three times a week for several weeks.

Pentostatin and Alemtuzumab

Another treatment option, Nipent (pentostatin), slows down DNA replication, cell growth, and division. Nipent is often given with Campath therapy if people do not achieve complete remission on Campath alone.

Fludarabine, Mitoxantrone, and Cyclophosphamide (FMC)

Another treatment, a combination of Fludara (fludarabine), Novantrone (mitoxantrone), and Cytoxan (cyclophosphamide) (collectively called FMC), may be followed by the use of Campath.

Stem Cell Transplantation

After a person achieves complete remission, a hematopoietic stem cell transplantation is recommended. Hematopoietic stem cell transplants help reduce the rate of relapse. However, not all people living with T-PLL are eligible for stem cell transplants. People who are older, have other complicating conditions, or don’t respond well to therapy may not be a good fit for a stem cell transplant.

Clinical Trials and Investigative Therapies

Other treatments for T-PLL are being designed and studied. Venclexta (venetoclax), which keeps T cells from maturing and dividing, is being studied in clinical trials for T-PLL. New personalized medicine therapies, based on the specific genetic differences in cancer cells of each person living with T-PLL, are also in clinical trials. If you’re interested in clinical trials, talk to your doctor about what’s available and how you might enroll.

Testing To Evaluate Treatment Progress

Throughout treatment, doctors will repeatedly perform blood counts, differential counts, and physical exams to measure how well treatment is working. Additional tests, such as bone marrow aspirates and biopsies, will also be used to evaluate effectiveness.

During a bone marrow aspiration, a needle is used to take a small amount of fluid from the bone marrow. A bone marrow biopsy is also usually taken to determine whether the bone marrow has cancerous cells. An effective treatment will decrease or eliminate the cancerous cells in the bone marrow over time. At the end of treatment, a bone marrow aspirate and biopsy are required to confirm complete remission. Other tests to check for cancer cell characteristics or infection are also done throughout treatment.

Prognosis of T-Cell Prolymphocytic Leukemia

Studies have found that, following treatment, complete remission rates vary from 60 percent to 80 percent in people living with T-PLL. However, relapse after a short time is common. To achieve complete remission, these seven criteria must be met:

• The lymph nodes must return to normal size.
• The spleen and liver must return to normal size.
• There must be no T-PLL-related symptoms.
• White blood cell count in the circulating blood must return to the normal ranges.
• There must be no cancerous cells in the bone marrow.
• There must be no cancerous cells or fluid buildup in the skin, lungs, or abdomen.
• The bone marrow must return to normal function.

Remission is confirmed by a physical examination, blood tests, radiology, and evaluation of bone marrow samples. After complete remission, your doctor should schedule follow-up visits to perform blood counts and physical exams every four to six weeks. Frequent follow-up visits can help your health care team catch any disease relapse early on, but it should be noted that T-PLL is harder to treat after relapse.

Low response rate to treatment after relapse makes the overall prognosis for T-PLL poor. The average life expectancy for T-PLL from the time of original diagnosis is 19 months.

Talk With Others Who Understand

A cancer diagnosis is a challenging time. It may help to have the support of others who can better understand your experience. MyLeukemiaTeam is the social network for people living with leukemia and their loved ones. Members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with T-cell prolymphocytic leukemia? Share your experience in the comments below, or start a conversation by posting on MyLeukemiaTeam.