Prolymphocytic leukemia

Synonyms

1

Overview

Prolymphocytic leukaemia is a specific type of leukaemia. Prolymphocytic leukaemia affects B lymphocytes in about four out of five case. About one in five cases of PLL affects T lymphocytes. The cells seen in the blood are large immature lymphocytes called prolymphocytes. PLL is similar to CLL but affects a more immature cell type.

Prolymphocytic leukemia is divided into two types according to the kind of cell involved: B-cell prolymphocytic leukemia and T-cell prolymphocytic leukemia. It is usually classified as a kind of chronic lymphocytic leukemia.

B-cell prolymphocytic leukemia is a more aggressive, but still treatable, form of leukemia. The malignant B cells are larger than average. The name is commonly abbreviated B-PLL. It can involve deletions from chromosome 11 and chromosome 13. It has been suggested that some cases may represent a variant of mantle cell lymphoma. It has a relatively poor prognosis.

T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. It is involving a proliferation of immature white blood cells (prolymphocytes - T-cells).T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults.

Symptoms

General Symptoms:

  • Enlarged spleen
  • Tiredness
  • Weight loss
  • High level of prolymphocytes in blood
  • High level of prolymphocytes in bone marrow
  • Enlarged spleen
  • Tiredness
  • Weight loss
  • Enlarged lymph nodes
  • High level of prolymphocytes in blood
  • High level of prolymphocytes in bone marrow

Symptoms of T-cell-prolymphocytic leukemia

Patients typically have systemic disease at presentation, including hepatosplenomegaly, generalized lymphadenopathy, and skin infiltrates.

Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow, spleen, liver, skin. A high lymphocyte count (> 100 x 109/L) along with anemia and thrombocytopenia are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.

Causes

In most cases of PLL there is no obvious cause.

Risk factors:

  • Age: Like most forms of cancer PLL is more common in older people
  • Being male: PLL affects slightly more males more than females
  • CLL: A small proportion of cases of B-PLL affects people who have already been diagnosed with CLL.

Diagnosis

Patients with PLL often have a very high white cell count at diagnosis. There is a condition called mixed CLL/PLL in which there are prolymphocytes present but these make up less than half of the lymphocytes in the blood. PLL is diagnosed when more than half of the lymphoid cells in the blood are prolymphocytes. Specialised tests are needed to distinguish between B-PLL and T-PLL.

Most patients with PLL will have bone marrow samples taken to confirm the diagnosis and to help to determine exactly what type of leukaemia a patient has. A bone marrow sample may not be necessary if treatment is not being started, but it is often valuable to have an initial sample to compare with later samples. More specialised tests are often done at the same time.

Blood samples will be taken to test for any problems with the liver, kidneys or other organs. Some blood tests and scans will be repeated to check for the response to treatment and any complications. Other tests are usually only done at diagnosis.

Blood tests and bone marrow samples may be repeated during treatment to monitor response.

Prognosis

This form of leukemia is rapidly progressive and usually responds poorly to therapy. The median survival time is about 7 months.

T-PLL is an aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumab, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.

Treatment

Some patients with PLL do not need to start treatment immediately after diagnosis. If patients are not being treated they have regular check-ups. This is known as "watchful waiting" or "active monitoring". Treatment is started when there is evidence of progression or when symptoms are causing distress.

PLL is not considered curable with standard treatments; with the possible exception of stem cell transplants in a small number of younger and/or fitter patients.

The main ways in which PLL is treated are:

  • Chemotherapy: Cell-killing drugs
  • Biological therapy: Treatments which use the immune system to destroy leukaemia cells. Often these use antibodies against markers on the PLL cells – these are known as monoclonal antibodies
  • Radiation therapy: Sometimes given locally to relieve symptoms caused by swollen spleen
  • Stem cell transplant: A small minority of younger/fitter patients may be given a stem cell transplant (bone marrow transplant). This is done using healthy stem cells from a donor

Chemotherapy is the use of cell-killing drugs. These kill the cancer cells and/or stop them from dividing. Chemotherapy is usually given in blocks or 'cycles' of treatment. One cycle of treatment will consist of a series of doses of chemotherapy followed by a break for the healthy cells to recover.

Chemotherapy is normally given as a combination of drugs. The details of your treatment 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.

Patients will be given detailed information about any likely side effects before you start treatment.

For B-cell prolymphocytic leukemia splenic irradiation has been used in the treatment.

Most patients with T-cell prolymphocytic leukemia require immediate treatment. T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (COP), and vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin (VAPEC-B).

Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment. Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.