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					           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.