FRC in High-Risk CLL Patients

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Again, from ASH:

[4917] Clinical Management of High Risk chronic

lymphocytic leukemia (CLL) with Fludarabine, Rituxan®

and Cyclophosphamide (FRC) Regimen.

Muhammad S. Shurafa, Ding Wang, VanDyke, Koichi

Maeda, T. Alaman-Canoso, Nalini Janakiraman,

Rajneesh Nath, Anne Wiktor, Baldy

Hematology/Oncology; Pathology; Genetics, Henry Ford

Hospital; phine Ford Cancer Center, Detroit, MI,

USA

We report the results of treatment of 11 complicated

Cll patients with FRC.

Ten patients have previously been treated for CLL and

9 of those have received fludarabine. Six subjects had

complicating autoimmune hemolytic anemia and 3 had

immune thrombocytopenia. Three were post splenectomy

for splenic pain or autoimmune disease.

One of the 11 patients who had very short doubling

time and bulky disease at presentation progressed

after the first treatment cycle. He was treated with

more intensive chemotherapy and was referred for

allogeneic stem cell transplantation. Another patient

with bulky disease failed to improve and died from

advanced disease.

There were 9 responses characterized by disappearance

of adenopathy, organomegaly and lymphocytosis. Mild

anemia persisted in 3, while pancytopenia developed in

another 3 patients. However, all of these six patients

remain transfusion independent and infection free.

Autoimmune hemolytic anemia persisted but to a milder

degree in 2 subjects who require a transfusion

occasionally. One of these two patients developed pure

red cell aplasia and was treated with intravenous

immunoglobulins. The other patient could not tolerate

his treatments very well because of co-existing

myelodysplastic syndrome (MDS) and the autoimune

hemolytic anemia. He did show a response nevertheless.

Another patient could not complete his scheduled

treatments because of hypersplenism and possible MDS.

Four patients developed changes consistent with MDS at

the end of the treatment which to date have been with

no consequence.

Routine and interphase cytogenetic remissions were

documented in 6/9 while new chromosomal aberrations

developed in 3 patients. Residual CLL was detected by

flow-cytometry in 5/9 patients even though they were

in cytogenetic and/or morphologic remission. 7/9

patients still show lymphoid aggregates in the bone

marrow biopsy and therefore were diagnosed with

nodular partial remissions.

We conclude that FRC regimen is effective in heavily

pretreated and complicated CLL with high response and

complete remission rates. Cytogenetic,

immunophenotypic and histologic remissions are

possible. However the remission status depends on the

diagnostic testing method employed. The significance

of the minimal residual disease detected by

flowcytommetry needs to be clarified. The diagnosis of

nodular partial remission should not be made without

immunophenotypic characterization of the bone marrow

lymphoid aggregates.

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