Prolymphocytic leukemia (PLL) is a rare form of leukemia that mainly affects older adults and not children. It advances rapidly, and people with PLL generally have a poor outlook. However, current research may offer new options for targeted treatment.
PLL is a rare form of typically aggressive blood cancer affecting mainly people in their 60s. The blood cells involved are the B or T white blood cells. These are cells that help the immune system fight infection and viruses.
Unlike more common forms of leukemia, PLL tends to advance rapidly, and those with the condition have a poor outlook. People usually improve with treatment, but over time the cancer comes back. As researchers understand more about the disease, new treatments are emerging.
This article describes the symptoms, diagnostic procedures, and available treatments of PLL.
PLL occurs when white blood cells called prolymphocytes multiply out of control in the bone marrow and later in the blood and other organs. PLL is related to the more common form of leukemia called chronic lymphocytic leukemia (CLL).
In PLL, the cancer cells tend to grow and spread faster than those in CLL. The affected cells are immature forms of B lymphocytes (B cells) or T lymphocytes (T cells).
The most common form of PLL is B cell prolymphocytic leukemia (B-PLL), which accounts for 80% of PLL cases. T cell prolymphocytic leukemia (T-PLL) accounts for 20% of PLL cases. However, both forms are extremely rare.
Both subtypes of PLL have been recognized by the World Health Organization (WHO) classification system as distinct from CLL.
Although B-PLL and T-PLL share some symptoms, they are distinct diseases.
The defining characteristic of B-PLL is when more than 55% of the lymphocytes in the circulating blood are prolymphocytes or when a majority of the lymphocytes in a lymph node or bone marrow sample are prolymphocytes.
It is also characterized by:
- an enlarged spleen
- elevated white blood cell counts
- limited or no lymph node involvement
Other symptoms of B-PLL may include:
T-PLL differs from B-PLL in that it may involve the lymph nodes and the skin, while B-PLL generally does not.
Symptoms of T-PLL may include:
The onset and development of B-PLL and T-PLL are well-researched, though much remains to be known. The cause of PLL is not yet totally understood.
B-PLL is thought to develop when a slow-growing B cell cancer, such as CLL or MCL, transforms into B-PLL. The disease is not thought to appear initially on its own.
Possible genetic causes of B-PLL are largely unknown, although abnormalities in the TP53 gene and the MYC gene have been noted.
T-PLL develops when a healthy T cell transforms into a leukemia cell, thought to be the result of chromosomal abnormalities and mutations in the genes of the T cell. Recent DNA sequencing has identified gene mutations in the JAK-STAT pathway that may relate to T-PLL.
PLL is an extremely rare form of cancer that primarily affects people in their 60s. It develops slightly more often in males than in females, and it does not usually occur in children.
PLL accounts for less than 2% of all lymphoid leukemia cases in adults in the United States. Lymphoid leukemia is a type of cancer that starts in the lymphocyte cells.
Survival rates for PLL cases vary depending on how aggressive the cancer is, meaning how rapidly it progresses.
According to a
A person should always talk with their doctor about their own individual circumstances and survival factors. New treatments are always in development to improve the outlook for these conditions.
Diagnosis of both types of PLL remains complex and challenging. Researchers do not completely understand the pathology of the disease, and test results can mimic those of other cancers, such as CLL and MCL.
Also, since the diseases are rare, medical professionals do not see cases often. One researcher noted that clinicians may see one person with the condition every 5–10 years. This can make recognition of the disease difficult.
However, once a doctor diagnoses PLL, distinguishing between the B cell and T cell subtypes can be done through observing physical developments, immunophenotyping (using antibodies to identify cells), and molecular genetic testing.
Doctors generally use a variety of tests to diagnose PLL. Tests may vary for B-PLL and T-PLL. Tests might include:
- complete blood count (CBC)
- peripheral blood smears, in which a medical professional examines a drop of blood under a microscope
- bone marrow biopsy
- evaluations of liver and kidney function
- immunophenotyping, in which antibodies are used to identify cells
- chromosome analysis, which looks for genetic abnormalities inside chromosomes
- imaging studies, including X-ray and CT scan
Doctors usually do not begin treatment for PLL until either a person has symptoms or the disease progresses. Until then, treatment is usually “watch and wait,” or active monitoring, which includes monthly physical exams and blood tests.
Only 10–15% of people do not have symptoms when they receive a PLL diagnosis. At this point, doctors advise anticipation and preparation for disease progression. They typically warn that the asymptomatic period is temporary and that progression is inevitable. When progression does occur, it will most likely be rapid.
The only potential cure comes from a stem cell transplant, officially called hematopoietic stem cell transplantation (HSCT). This procedure is only possible for people who experience remission after a first round of drug therapy. This combination treatment is called consolidative therapy.
Even after consolidation with HSCT, long-term remission happens only in a minority of cases. Doctors suggest that eligible people diagnosed with PLL take part in clinical trials where new drugs or new drug combinations are tested.
In addition to HSCT, treatments for B-PLL and T-PLL vary according to the aggressiveness of the disease. The following therapies may be used.
For B-PLL, treatments may include:
- chemotherapy and immunotherapy
- the monoclonal antibody drug alemtuzumab (Lemtrada), delivered intravenously
- the new drugs ibrutinib (Imbruvica) and idelalisib (Zydelig)
For T-PLL, treatments may include:
- the monoclonal antibody drug alemtuzumab (Lemtrada)
- bone marrow transplant
PLL is a fast-growing cancer of the blood that affects certain white blood cells called prolymphocytes. It can involve either the B cells or T cells. The outlook is generally poor with conventional therapies.
As researchers understand the disease better, new treatments and diagnostic methods are emerging that may improve the outlook for people with PLL.