- complete remission rates of
25-30% with overall response rates of
75-80%
- Median time to progression
among responders was 30-36 months
The reason for using
combinations of drugs is based upon evidence
of additive or synergistic apoptosis
(normal, planned cell death), or inhibition
of DNA repair, a potent activity of purine
analogs. A series of clinical trials have
been done at M D Anderson Cancer Center in
Houston, Texas, using fludarabine with
prednisone (FP), fludarabine with
mitaxantrone (FM), fludarabine with
cyclophosphamide (FC). FC has been used
alone or with granulocyte macrophage cell
stimulating factor (GM-CSF) or with
amifostine. The addition of other agents to
fludarabine in front-line therapy has not
substantially improved the rate of complete
remission, but the overall response rate has
been modeslty increased. However, only in
patients who have been previously treated
with chlorambucil, FM and FC combinations
have shown superior response rates and
significantly prolonged survival compared
with fludarabine alone or with
prednisone. New
combinations have been developed to make use
of monoclonal antibodies. FC has been
combined with rituximab (FCR) and the
complete remission rate for FCR is 60% with
an overall response rate of 93%. There has
been no enhanced infectious toxicitity or
episodes of hemolytic myelosuppression with
the combination programs.
Daniel Catovsky, "When is
CLL not CLL?"
Patients with lymphocytosis, but without the
characteristic immunophemotypic and
morphologic features of CLL can be diagnosed
with other lymphoproliferative disorders. [Immunophenotyping is the
process of classifying cells, based on structural and functional
differences-the ways the cells are put together and what the cells
do. Morphology is the study of the configuration or the structure of
cells.] Difficulties arise when when the findings of microscopic
examination closely resemble CLL. In his laboratory, using several
thousand samples of patients with lymphocytosis, about 50% of them had
CLL. A minority have T-Cell leukemia, but they can be easily
identified by T-cell markers. T- prolymphocytic leukemia (T-PLL) and
large granulocytic leukemia are T-cell disorders that are often
confused with T-CLL. The most common problem arises when patients with
low-grade non-Hodgkin's lymphomas (NHL) present with leukemias. About
30% of the lymphocytosis cases have this problem. Mantle cell lymphoma
in it's leukemic phase is another disease that must be ruled
out.
An important element to consider is the CLL Score (Moreau et
al., American Journal of Clinical Pathology 1997;108:378-82)
which includes the five markers: CD5, CD 23, FMC7, CD79b, and the
intensity of Smig. Close to 90% of those with CLL score 4 or 5, while
those with Mantle cell lymphoma score only 1 to 3. Tissue histology is
not always available in patients with a large spleen. [Histology is
the study of cells and tissue on the microscopic level.] Bone marrow
biopsy is useful since it can identify characteristic cell clefts and
it can show cyclin D1 by immunochemistry. Flow cytometry and FISH
testing are also helpful in distinguishing CLL from other lymphocytic
disorders. [FISH is using a DNA or RNA probe to detect the presence of
the complementary DNA sequence in cloned bacterial or cultured cells.]
Splenic lymphoma with villous lymphocytes (SLVL) score only 0-1, and
the cells are CD5- and CD23-. SLVL cells have a distinct
morphology. The abnormal chromosome patterns
typical of CLL, such as 13q14 deletion, 11q23 deletion, and 6q21
deletion are also seen in the leukemic phase of NHL. Trisomy 12 is not
unique to CLL either. Therefore positive FISH evidence of ALL does not
help in difficult cases. One must rely on the morphological and
immunological features one sees in the bone marrow and or lymph node
histology. The presence of proliferating centers with
para-immunoblasts and prolymphocytes is seen only in CLL. It is
imperative to make a correct diagnosis and non-CLL conditions should
be clearly recognized by using all the elements given here.
Disclaimer
The presence of any site on this list does not
imply endorsement. Please discuss any information or treatment
options you gain from this page with your personal physician.Every
effort has been made to ensure that the links on this page are in
working order, however, the web moves rapidly, so please contact us if you find a link that is
inoperable.
|
HOME
::
ABOUT THIS SITE
::
CONTACT
|
|
