1. Chapter 17
Chronic Leukemias

2. Chronic Lymphocytic Leukemia

3. CLL
Chronic – mature cells, signs and symptoms develop gradually, and often discovered accidentally; May not be diagnosed for years!
Lymphocytic – lymphoproliferative disorder
Leukemia – replacement of normal bone marrow with neoplastic cells, causing anemia, thrombocytopenia, and neutropenia

4. CLL Most common form of leukemia in older adults
Patients usually in their 50’s when diagnosed
Average survival time is 5 years; May take an aggressive course with only 1-2 years of survival time
Many CLL patients die from infections
No known specific etiologic agent or cause for CLL
Most frequently a neoplasm of B-lymphocytes (rarely T cells)
Lymphocytes are small and have relatively mature, well-differentiated appearance
Bare nuclei, called “smudge cells” frequently found

5. CLL
Will develop altered humoral immunity resulting from suppression of all classes of immunoglobulins, leading to hypogammaglobulinemia; Subsequent increase in susceptibility to infections
Many patients (15-35%) develop autoimmune disorders and produce autoantibodies to neutrophils, platelets (i.e. ITP), or RBCs (WAIHA)
Have significantly impaired immunologic activity

6. CLL Normal adult peripheral blood:
B-cell lymphocytes 30% with surface immunoglobulins
T-cell lymphocytes 70% without surface immunoglobulins
Very important to differentiate which type of lymphocytes are involved in the CLL (B cells or T cells)
Diagnosis of CLL can be done morphologically, but distinguishing between T-cell and B-cell CLL requires testing for cluster differentiation (CD) antigens

7. CLL
Malignant B cells of CLL do not progress to the final stages of development, the plasma cells; Appear to stop developmentally at earlier B-lymphocyte stage of development
CLL usually presents with elevated WBC count with many lymphocytes
Not usually curable with available therapy
Treatments include bone marrow transplants, radiation, chemotherapy, and intravenous gamma globulin to help prevent bacterial infections

8. CLL Laboratory Results
Anemia is usually normochromic, normocytic with a normal to low reticulocyte count
Autoimmune hemolytic anemia may develop (positive DAT and elevated indirect bilirubin)
Often a decreased PLT count, due to bone marrow replacement of megakaryocytic precursors or platelet antibodies
Lymphocytes may be morphologically identical to normal mature lymphocytes, or may have a “soccer-ball” type of staining appearance
Immune dysfunction and hypogammaglobulinemia is usually present, with proliferating B-cells

9. Chronic Myelocytic Leukemia

10. CML Also known as Chronic Granulocytic Leukemia (CGL)
A clonal myeloproliferative disorder of hematopoietic pluripotent cell transformation characterized by marked leukocytosis and excessive production of granulocytes at all stages of maturation
Is associated with chromosomal abnormality called Philadelphia Chromosome; % of patients with CML carry Philadelphia Chromosome, which is the joining of chromosomes 9 and 22
Usually occurs between ages of (“adult leukemia”)
CML accounts for 25% of all leukemia cases
Often discovered accidentally during routine physical
Mean survival is 3-4 years after diagnosis
Most patients die from complications arising from blast cell crisis
Only treatment is bone marrow transplant

11. CML A clonal stem cell disorder
Causative agents include exposure to ionizing radiation, administration of cytotoxic drugs, and exposure to viruses
Cause of CML is unknown in 95% of cases
Not inherited; Appears to be acquired, and the Philadelphia Chromosome is not present in non-hematopoietic tissues

12. Philadelphia Chromosome in CML
Philadelphia (Ph) chromosome found in neutrophil, monocyte, erythrocyte, platelet, and basophil precursors from CML patient’s blood and bone marrow
Helps in defining translocation that produces Ph chromosome as clonal abnormality
Specific notation is t(9;22)
Main portion of the long arm of chromosome 22 is deleted and translocated to distal end of long arm of chromosome 9, and a small part of chromosome 9 reciprocally translocates to the broken end of chromosome 22
Provides subsequent progeny with growth advantage over normal cells
Also, the expression of the anti-apoptosis gene, which is responsible for cell death, is altered

13. Laboratory Findings in CML
Increased load of myeloid cells, often with WBC count over 100 x 109/L
Will see all stages of maturation, from blasts to mature segs; However, segmented neutrophil and myelocyte are the most numerous forms; Will see left shift
Eosinophil, basophil and platelet numbers may be increased
Normochromic, normocytic anemia with Hgb usually < 10 g/dL
Bone marrow hypercellular with marked myeloid hyperplasia (M:E ratio of 10:1, instead of the normal 3:1)
Low to absent leukocyte alkaline phosphatase (LAP)