Prolymphocytic Leukaemia (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.

Risk factors

• 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.

B-PLL

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

T-PLL

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.

B-PLL

Drug Treatment

• 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.

T-PLL

Drug treatment

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.

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?

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