252
U N I T 3
Hematopoietic Function
tissue.
20–26
Bone marrow biopsy may be used to deter-
mine the molecular characteristics of the leukemia, the
degree of bone marrow involvement, and the morphol-
ogy and histology of the disease. Cytogenetic studies,
which are used to determine chromosomal abnormali-
ties, are one of the most powerful prognostic indicators
in acute leukemia. In ALL, the staging includes a lumbar
puncture to assess CNS involvement. Imaging studies
that include computed tomography (CT) of the chest,
abdomen, and pelvis may also be obtained to identify
additional sites of disease.
Several types of treatment may be used for the man-
agement of ALL and AML with the primary treatment
being chemotherapy. Treatment of ALL in childhood
represents one of the great success stories in oncology.
During the past decade, advances in ALL therapy have
led to 5-year survival rates of greater than 80% in chil-
dren.
19
Other age groups tend to do less well, with only
about 30% to 40% of adults achieving long-term sur-
vival. Chemotherapy leads to remission in over 50%
of persons with AML, but the overall survival rate is
less than 30%.
4
Bone marrow or stem cell transplanta-
tion may be considered for persons with ALL and AML
who have failed to respond to other forms of therapy.
17
Because of the risk of complications, bone marrow
transplantation is not usually recommended for patients
older than 50 to 55 years of age.
Chronic Leukemias
In contrast to acute leukemias, chronic leukemias are
malignancies involving proliferation of more fully dif-
ferentiated myeloid and lymphoid cells.
4,7
As with acute
leukemia, there are two major types of chronic leuke-
mia: chronic lymphocytic leukemia (CLL) and chronic
myeloid (myelogenous) leukemia (CML). Chronic lym-
phocytic leukemia accounts for about one third of all
leukemias and is mainly a disorder of older persons. The
average age at time of diagnosis is approximately 72
years. It is rarely seen in people younger than 40 years of
age, and is extremely rare in children.
30
Chronic myeloid
(myelogenous) leukemia accounts for 10% to 15% of
all leukemias. As with CLL, it is predominantly a dis-
order of older adults, with an average age of approxi-
mately 67 years at the time of diagnosis.
Chronic Lymphocytic Leukemia.
Chronic lymphocytic
leukemia, a clonal malignancy of B lymphocytes, is the
most common form of leukemia in adults in the Western
world. In the past, CLL was viewed as a homogeneous
disease of immature, immune-incompetent, minimally
self-renewing B cells, which accumulated because of
faulty apoptotic mechanisms. Chronic lymphocytic leu-
kemia is now becoming viewed as two related entities
based on aggressiveness of the disease. Some persons
with CLL survive for many years without therapy and
eventually succumb to unrelated diseases, whereas oth-
ers have a rapidly fatal disease despite aggressive ther-
apy. The two entities are thought to reflect differences in
the expression of cell surface CD markers (e.g., CD38)
in immunoglobulin variable (V) gene mutations.
30–32
This difference is rarely present in normal B cells but
is found in persons with CLL. Persons whose CLL cells
have mutated forms of the immunoglobulin gene gener-
ally have a more indolent form of the disease; these cells
express low levels of the surface antigen.
The clinical signs and symptoms of CLL are largely
related to the progressive infiltration of the bone marrow
and lymphoid tissues by neoplastic lymphocytes and to
secondary immunologic defects. Persons with the indo-
lent form of CLL are often asymptomatic at the time of
diagnosis, and the increase in lymphocytes is noted on a
complete blood count obtained for another, unrelated dis-
order. As the disease progresses, lymph nodes gradually
increase in size and new nodes are involved, sometimes
in unusual areas such as the scalp, orbit, pharynx, pleura,
gastrointestinal tract, liver, prostate, and gonads. Persons
with the aggressive form of CLL experience a more
rapid sequence of clinical deterioration characterized by
increasing lymphadenopathy, hepatosplenomegaly, fever,
abdominal pain, weight loss, progressive anemia, and
thrombocytopenia, with a rapid rise in lymphocyte count.
Hypogammaglobulinemia is common in CLL, espe-
cially in persons with advanced disease. An increased
susceptibility to infection reflects an inability to produce
specific antibodies and abnormal activation of comple-
ment. The most common infectious organisms are those
that require opsonization for bacterial killing, such as
Streptococcus pneumoniae, Staphylococcus aureus,
and
Haemophilus influenzae.
The diagnostic hallmark of CLL is isolated increase
in lymphocytes. The white blood cell count is usually
greater than 20,000/
μ
L and may be elevated to several
hundred thousand. Usually, 75% to 98% are lympho-
cytes. Tests to determine the presence of mutated forms
of the immunoglobulin gene (which currently can be
detected only in research laboratories) and expression
of the CD38 surface antigen may be used to determine
whether the leukemia is the indolent or aggressive type.
31
Treatment of CLL usually depends on the presence of
prognostic indicators.
31
Persons with the low-risk or
indolent form of CLL usually do not require specific
treatment for many years after diagnosis and eventually
die of apparently unrelated causes. Many persons with
intermediate-risk disease may remain stable for many
years as well, whereas others may develop complications
and need treatment within a few months. Most persons
with high-risk CLL require combination chemotherapy
at the time of diagnosis. In younger patients with aggres-
sive disease, an allogeneic ablative (destruction of bone
marrow cells by irradiation or chemotherapy) or non-
myeloablative stem cell transplant is a treatment option.
Chronic Myelogenous Leukemia.
Chronic myeloid
(myelogenous) leukemia is a disorder of the pluripo-
tent hematopoietic progenitor cell. It is characterized
by excessive proliferation of marrow granulocytes,
erythroid precursors, and megakaryocytes.
4,7,33–38
The
CML cells harbor a distinctive cytogenic abnormality,
the previously described
Philadelphia chromosome.
It is
generally believed that CML develops when a single, plu-
ripotent hematopoietic stem cell acquires a Philadelphia
