Lymphoid Malignancies

Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is caused by a clonal proliferation of B lymphocytes. It is the most common chronic leukemia with a predilection for men over women. Most patients are older, over 50 years of age.1 Small lymphocytes begin to accumulate in the spleen, lymph nodes, and bone marrow to a high degree and eventually spill into the peripheral blood. These malignant lymphocytes will show CD15, CD19, CD20, and CD22 antigen markers as well as exhibit a low level of surface immunoglobulin (SIg) and CD5, a marker usually reserved for T cells. Chromosomal abnormalities include chromosomes 11, 12, and 13 in over 82% of patients.2 Trisomy 12 is reported in almost half of all CLL patients and is associated with a poor prognosis.2 The presenting symptoms of this disease are fairly unremarkable (fatigue, pallor, weight loss), and for this reason, it is often discovered by accident, as a result of other complaints. However, lymphadenopathy is the most common initial symptom.3 The white counts are exaggerated with many over 100,000 X 109/L. The M:E ratio is 10 or 20:1, and the bone marrow and peripheral blood present a monotonous tapestry of mature lymphocytes to the exclusion of other normal elements in the blood or bone marrow.

Figure 13.1 Bone marrow view of chronic lymphocytic leukemia. Compare the nRBCs at the arrow with mature lymphocytes.

Disease Progression in Chronic Lymphocytic Leukemia

The peripheral blood smear shows exclusively small lymphocytes intermixed with few lymphoblasts. The lymphocytes show certain homogeneity in morphology with a heavily clumped chromatin combined with round and at times slightly indented nucleus. Figure 13.1 provides a comparison of nucleated red blood cells (nRBCs) and lymphocytes in CLL. Smudge cells may be present in the peripheral smear and are visualized as pieces of lymphocyte chromatin splashed across the peripheral smear. Because lymphocytes are fragile, smudge cells may arise in the process of making a peripheral smear where the cytoplasm is disrupted and the nuclear chro-matin strands are smudged across the smear in a basket shape or amorphous smudge (Fig. 13.2).

As the disease progresses, lymphocyte mass accumulates in the bone marrow and splenomegaly and

Figure 13.2 Chronic lymphocytic leukemia with smudge cells.

lymphadenopathy may develop. Anemia, thrombocytopenia, and neutropenia usually develop in the course of the disease, subsequent to lymphocytic involvement §

in the bone marrow. The altered immune function of the |

lymphocytes may lead to the complication of autoim- |

mune hemolytic anemia in 10% to 30% of individuals .§

with CLL. Spherocytes and nRBCs that appear in the J

peripheral smear of CLL individuals may be early indi- §

cators of the autoimmune hemolytic process. Erythroid J

hyperplasia is present in the bone marrow, and the »

direct antiglobulin test (which measures antibody 3

coating of the red cells) is positive. |

Immunological Function in Chronic Lymphocytic Leukemia and Treatment Options

The B lymphocytes present in CLL patients are long-lived and nonproliferating. Programmed cell death or apoptosis is a significant feature in most cell line progressions, but in 80% of CLL patients there is the presence of Bcl2, an antiapoptosis gene.4 Therefore, the survival of the dysfunctional B-cell clone is guaranteed. Additionally, the immunological function of these lymphocytes is compromised, with over 50% of patients showing a hypogammaglobulinemia. Patients experience bacterial or skin infections, particularly herpes zoster (shingles) and herpes simplex (cold sores), that can be painful and debilitating.5

Treatment options for CLL patients include irradiation for enlarged spleen and lymph nodes as a means to reduce discomfort and related symptoms.6 The most effective drug for reducing lymphocyte burden is flu-darabine, a cytotoxic drug that induces apoptosis.7 Other therapies include alkylating agents, monoclonal antibodies, and possibly allogeneic stem cell transplants. Table 13.1 depicts the Rai staging systems and survival projections. The Rai staging system was designed by Dr. Rai in 1970 and modified in 1987. These systems divide patients into risk categories and provide survival statistics. Staging systems are developed to analyze patient

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