Factsheet Transformation of CLL (Richter’s Syndrome and Prolymphocytic transformation) The titles in this series are intended to provide general information about the topics they describe. In many cases the treatment of individual patients will differ from that described. At all times patients should rely on the advice of their specialist who is the only person with full information about their diagnosis and medical history. B-cell prolymphocytic leukaemia but the lymphoma may arise transformation and Richter’s syndrome are from a different cell to the leukaemia. In relatively rare conditions which arise in a the latter case the lymphoma could be small proportion of patients with Chronic regarded as a second cancer arising by Lymphocytic Leukaemia (CLL). chance. Prolymphocytic leukaemia can also occur as a separate disease unrelated to pre- existent Chronic Lymphocytic Leukaemia. Causes There is a Leukaemia Research Fund booklet available on Chronic Lymphocytic Leukaemia. CLL, PLL and Richter’s syndrome are all diseases of later life. Patients may present with PLL but this also occurs, like Prolymphocytic Leukaemia Richter’s syndrome, in patients who already have CLL. The diseases are seen more commonly in men than in women. Prolymphocytic leukaemia (PLL) is a rare form of lymphocytic leukaemia There are no obvious causes for accounting for about 1% of all CLL cases. the transformation of CLL to PLL or Most PLL patients present with the Richter’s syndrome. The causes of de- disease when first seen (de-novo PLL) but novo PLL are not known, but the risk some will have initially been diagnosed factors are thought to be the same as for with CLL which has transformed into a CLL. disease resembling PLL. Ten percent of patients who have The abnormal lymphocytes seen in PLL chronic lymphocytic leukaemia will have are called prolymphocytes. The diagnosis their illness transform into a disease is PLL rather than CLL if more than about resembling prolymphocytic leukaemia. As half of the leukaemic cells are in CLL, the malignant cells in PLL and prolymphocytes. If there are Richter’s syndrome are B-cells Another prolymphocytes present but these make condition called T-cell PLL has no relation up less than half of all the abnormal cells with CLL or B-PLL and tends to run an the condition is called mixed CLL/PL. aggressive clinical course. There is no clear link between Richter’s Syndrome previous treatment for CLL and transformation into PLL or Richter’s Richter’s syndrome is the late syndrome. The age of patients with an development of a lymphoma in a patient initial diagnosis of PLL is on average who already has CLL. Laboratory tests slightly older than for CLL patients. It is show that usually the lymphoma comes possible that many of these patients may from the same population of cells as the have had undiagnosed CLL, possibly for many years, and that this had already transformed into PLL by the time they were diagnosed. Treatment All patients with PLL will need Signs and symptoms treatment. This differs from CLL in which many patients do not require treatment. A patient with PLL will typically have a very large spleen and a very high white count.Most patients do not have Unfortunately PLL tends to be more enlarged lymph nodes. Non-specific aggressive than CLL and is less symptoms like tiredness and weight loss responsive to therapy. The response to are common. treatment and overall survival tends to be somewhat better in those cases which Patients with Richter’s Syndrome arise in patients who did not previously typically present with increasing have CLL. The median survival in CLL is enlargement of lymph nodes, liver and about eight years and in “new” cases of spleen, fever, abdominal pain and weight PLL it is about three to five years. It is loss. They often have marked anaemia important to stress that median survival and low platelet counts leading to means that half of all patients will survive bleeding/bruising. longer than this, possibly many years longer. Diagnosis The new nucleoside analogue drugs fludarabine (Fludara) and chlorodeoxy-adenosine (Cladribine) have In the laboratory the appearance shown promising results in patients with B- of prolymphocytes in the blood film is quite cell PLL. Some patients with B-PLL and distinctive and the diagnosis is usually Richter’s syndrome benefit from obvious to an experienced haematologist. combination chemotherapy such as CHOP (which involves the four drugs Patients may be asked to have a cyclophosphamide, doxorubicin, vincristine bone marrow sample taken. This involves and prednisone). obtaining a small amount of marrow from inside the bone with a needle, and a In the unrelated condition T-cell sample from the bone itself showing the PLL treatment with the nucleoside structure of the bone marrow cavity. The analogue deoxy-coformycin (Pentostatin) first is known as a bone marrow aspirate, and a monoclonal (very specific) antibody the second as a bone marrow trephine. called CAMPATH-1H have resulted in The samples are usually obtained from the complete remissions and long survivors. A back of the hip bone, although the sternum minority of patients have, after complete (breast bone) may be used instead for remission, received an autologous bone marrow aspirates (but not for transplant with their own bone marrow or trephines). The procedure causes some peripheral blood stem cells. discomfort but does not take very long. The procedure is usually carried out with sedation as well as local anaesthetic. Prognosis Richter’s Syndrome patients will have enlarged lymph nodes. Samples are See above. taken from these nodes for laboratory tests. The form of lymphoma is most often either large-cell or immunoblastic lymphoma.