CHRONIC
LYMPHOCYTIC LEUKEMIA (CLL)
CLL is
a common malignancy of older adults; two thirds of all patients are older than
60 years of age at diagnosis. It is the most common form of leukemia in the
United States and Europe, affecting more than 120,000 people, but is rarely
seen in Asia. The average survival time for patients with CLL ranges from 14
years (early stage) to 2.5 years (late stage).
CLL
typically derives from a malignant clone of B lymphocytes (T-lymphocyte CLL is
rare). In contrast to the acute forms of leukemia, most of the leukemia cells
in CLL are fully mature. It appears that these cells can escape apoptosis (programmed cell death), with
the result being an excessive accumulation of the cells in the marrow and
circulation. The antigen CD52 is preva-lent on the surface of many of these
leukemic B cells. The disease is classified into three or four stages (two
classification systems are in use). In the early stage, an elevated lymphocyte
count is seen and can exceed 100,000/mm3. Because the lymphocytes are small, they can
easily travel through the small capillaries within the circulation, and the
pulmonary and cerebral complications of leukocytosis (as seen with myeloid
leukemias) typically are not found in CLL.
Lymphadenopathy
occurs as the lymphocytes are trapped within the lymph nodes. The nodes can
become very large and are sometimes painful. Hepatomegaly and splenomegaly then
develop.
In later
stages, anemia and thrombocytopenia may develop. Treatment is typically
initiated in the later stages; earlier treatment does not appear to increase
survival. Autoimmune complications can also occur at any stage, as either
autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP). In
the autoimmune process, the RES destroys the body’s own RBCs or platelets.
Many
patients are asymptomatic and are diagnosed incidentally during routine
physical examinations or during the course of treatment for another disease. An
increased lymphocyte count (lymphocytosis) is always present. The RBC and
platelet counts may be normal or, in later stages of the illness, decreased.
En-largement of lymph nodes (lymphadenopathy) is common; it can be severe and
sometimes painful. The spleen can also be enlarged (splenomegaly).
Patients
with CLL can develop “B symptoms,” a constellation of symptoms including
fevers, drenching sweating (especially at night), and unintentional weight
loss. These patients have defects in their humoral and cell-mediated immune
systems; therefore, infections are common. The defect in cellular immunity is
evi-denced by an absent or decreased reaction to skin sensitivity tests (eg, Candida, mumps), which is known as anergy. Problems with life-threatening
infections are common. Viral infections, such as herpes zoster, can become
widely disseminated.
In
early stages, CLL may require no treatment. When symptoms are severe (drenching
night sweats, painful lymphadenopathy), or when the disease progresses to later
stages (with resultant anemia and thrombocytopenia), chemotherapy with
corticosteroids and chlorambucil (Leukeran) is often used. Other useful agents
in-clude cyclophosphamide (eg, Cytoxan), vincristine (eg, Oncovin), and
doxorubicin (eg, Adriamycin). A significant number of pa-tients who do not
respond to these medications have achieved re-mission with fludarabine
(Fludara), and this medication is increasingly being used as front-line therapy.
The major side ef-fect of fludarabine is prolonged bone marrow suppression,
mani-fested by prolonged periods of neutropenia, lymphopenia, and
thrombocytopenia. Patients are then at risk for such infections as Pneumocystis carinii, Listeria, mycobacteria,
herpes viruses, andcytomegalovirus (CMV). The monoclonal antibody rituximab
(Rituxan) also has efficacy in CLL therapy. It is often used in com-bination
with other chemotherapeutic medications. Research has shown that the monoclonal
antibody alemtuzumab (Campath) targets the CD52 antigen commonly found on CLL
cells and that it is effective in clearing the marrow and circulation of these
cells without affecting the stem cells. Because CD52 is present on both B and T
lymphocytes, patients receiving alemtuzumab are at sig-nificant risk for
infection; prophylactic use of antiviral agents and antibiotics (eg,
trimethoprim and sulfamethoxazole [Septra]) is important and needs to continue
for a minimum of 2 months after the patient stops treatment. Because bacterial
infections are com-mon in patients with CLL, intravenous treatment with
immuno-globulin may be given to selected patients.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.