Chapter 17
Chronic Leukemias
1
Chronic Lymphocytic
Leukemia
2
CLL
► Chronic
– mature cells, signs and symptoms
develop gradually, and often discovered
accidentally; May not be diagnosed for 1015 years!
► Lymphocytic – lymphoproliferative disorder
► Leukemia – replacement of normal bone
marrow with neoplastic cells, causing
anemia, thrombocytopenia, and neutropenia
3
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
4
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
5
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
6
CLL
► Malignant
B cells of CLL do not progress to the
final stages of development, the plasma cells;
Appear to stop developmentally at earlier Blymphocyte 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
7
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
8
Chronic
Myelocytic Leukemia
9
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; 90-95% of patients with CML
carry Philadelphia Chromosome, which is the joining of
chromosomes 9 and 22
Usually occurs between ages of 30-50 (“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
10
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
11
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
12
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)
►
13