Blood cells are formed in the bone marrow, which is the spongy tissue found inside bones. Blood-forming stem cells divide to produce either more stem cells or immature cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
A myeloid stem cell becomes one of three types of mature blood cells:
- Red blood cells that carry oxygen to all tissues of the body.
- Platelets that form blood clots to stop bleeding.
- Granulocytes (white blood cells) that fight infection and disease.
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):
- B lymphocytes (B-cells) that make antibodies to help fight infection.
- T lymphocytes (T-cells) that help B lymphocytes make the antibodies to fight infection.
- Natural killer cells that attack cancer cells and viruses.
Prolymphocytic leukaemia (PLL) can be either:
- B-cell prolymphocytic leukaemia (B-PLL) – Present in 80% of patients with PLL and involves uncontrollable growth of B-cells.
- T-cell prolymphocytic leukaemia (T-PLL) – Present in 20% of patients with PLL and involves uncontrollable growth of T-cells.
The cells seen in the blood are large immature lymphocytes called prolymphocytes. PLL is similar to chronic lymphocytic leukaemia (CLL) but affects a less mature cell type.
What causes PLL?
In most cases of PLL, there is no obvious cause.
B-PLL generally occurs as a transformation of a slow-growing B-cell cancer, such as CLL or mantle cell lymphoma. B-PLL rarely occurs as a disease on its own, but it is not inherited and not contagious.
T-PLL is related to abnormal changes (mutations) in the genes of the T-cells that can cause a normal, healthy T-cell to become a leukaemia cell.
- B-PLL usually occurs in adults with a median age at diagnosis of 69 years and it is slightly more common in men than women.
- T-PLL affects adults with a median age at diagnosis of 61 years and is more common in men than in women.
Signs and Symptoms
Common signs and symptoms of B-PLL include:
- High lymphocyte count
- Enlarged spleen
- B-symptoms (i.e., fevers, night sweats or weight loss)
- Low red blood count (anaemia)
- Low platelet count
Common signs and symptoms of T-PLL include:
- Swelling of the lymph nodes
- Enlarged liver
- Enlarged spleen
- Night sweats and weight loss
- Skin lesions or rash
- Elevated white blood cell counts
- Low red blood cell counts (anaemia)
- Low platelet counts
Lymph nodes are more likely to be enlarged in T cell-PLL than in B-PLL. In T-PLL, there may be leukaemia cells in the skin.
There are no specific signs or symptoms that allow a diagnosis of PLL to be made.
Tests used to diagnose PLL include:
- Blood samples
- Peripheral blood smears
- Bone marrow biopsy
- Immunophenotyping (antibodies are used to identify cells based on the types of antigens or markers on the surface of the leukaemia cells)
- Chromosome analysis
- Computerised tomography (CT) or positron emission tomography (PET) scans
Diagnoses for the types of PLL require:
- B-PLL: More than 55% of the lymphocytes in the blood sample must be prolymphocytes, or if a lymph node or bone marrow sample is obtained, it must include a majority of lymphocytes that are prolymphocytes.
- T-PLL requires the blood or bone marrow sample to be analysed. T-PLL is very rare and the diagnosis is complex.
- Mixed CLL/PLL is a condition in which prolymphocytes are present in the blood but make up less than half of the lymphocytes.
Watch and Wait (or active monitoring)
Around 10-15% of PLL patients do not have symptoms at the time of diagnosis, and their treatment which is called watch and wait or active monitoring. This consists of delaying the start of treatment until signs and symptoms of the disease appear or progress. Frequent monitoring including blood tests is necessary so that treatment can be started if the disease starts advancing.
- Most chemo-immunotherapy drug combinations include:
- FCR: fludarabine, cyclophosphamide and rituximab
- BR: bendamustine and rituximab
- Patients who have a mutation in the TP53 gene are often resistant to conventional drugs and may require the monoclonal antibody drug alemtuzumab.
- New drugs that target B-cell signalling which stops the B-cells multiplying include ibrutinib and idelalisib for patients who are unable to tolerate FCR and/or who have TP53 gene mutations.
Haematopoietic stem cell transplantation
- For patients who show remission of their B-PLL after the first cycle of drug therapy, a haematopoietic stem cell transplantation (HSCT) may be able to achieve a cure. However, many patients are not well enough for initial treatment needed for an HSCT. Reduced-intensity drugs to prepare patients for an HSCT are now available.
- Patients are also encouraged to take part in clinical trials where new drugs or new drug combinations are tested. Clinical trials are conducted in most countries under strict conditions to help determine if new cancer treatments are more effective than the currently available treatments and safe for patients.
Drug treatment options for patients with symptomatic T-PLL include:
- Intravenous (IV) alemtuzumab, generally given three times a week for four to eight weeks, depending on the specific patient and disease.
- IV alemtuzumab plus pentostatin.
- FMC: fludarabine, mitoxantrone and cyclophosphamide followed by IV alemtuzumab.
- Nelarabine can be useful for treating T-PLL.
Haematopoietic stem cell transplantation
For patients who show remission of their T-PLL after the first cycle of treatment, a HSCT may be able to achieve a cure. The position regarding suitability of the patient for a HSCT and encouragement to participate in clinical trials is the same as for patients with B-PLL.
The details of treatment options available will vary depending on the type of PLL, age and general fitness. Patients will be given a chance to discuss treatment options and detailed information on the treatment plan before it starts. The side effects of treatment vary between different types of treatment and different patients.
Questions to ask your doctor about PLL
We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling.
Here are some questions that may be useful to ask your doctor:
- How would I know if I had PLL?
- What tests will I need to have?
- What will the tests show?
- How long will the results take?
- How rare is PLL?
- What sort of treatment will I need?
- How long will my treatment last?
- What will the side effects be?
- Is there anything I should or should not eat?
- Will I be able to go back to work?
- Where can I get help with claiming benefits and grants?
- Where can I get help dealing with my feelings?
Published: March 2021
Review date: March 2024