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Chapter
17
CHRONIC LEUKEMIAS
 2

Chronic
Lymphocytic
Leukemia
 CLL 3

 Chronic – mature cells, signs and symptoms develop gradually,

and often discovered accidentally; May not be diagnosed for
10-15 years!
 Lymphocytic – lymphoproliferative disorder
 Leukemia – replacement of normal bone marrow with neoplastic
cells, causing anemia, thrombocytopenia, and neutropenia
CLL 4

 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
 CLL 5

 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
 CLL 6

 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
 CLL 7

 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
 CLL Laboratory Results 8

 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
CML 10

 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
CML 11

 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
Philadelphia Chromosome 12

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
Laboratory Findings in 13

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)