C h a p t e r 1 1
Disorders of White Blood Cells and Lymphoid Tissues
253
chromosome. Although CML originates in the pluripo-
tent stem cells, granulocyte precursors remain the domi-
nant leukemic cell type.
The clinical course of CML is commonly divided into
three phases: (1) a chronic phase of variable length, (2)
a short accelerated phase, and (3) a terminal blast crisis
phase. The onset of the chronic phase is usually slow, with
nonspecific symptoms such as weakness and weight loss.
The most characteristic laboratory finding at the time of
presentation is leukocytosis with immature granulocyte
cell types in the peripheral blood. Anemia and, eventually,
thrombocytopenia develop. Anemia causes weakness,
easy fatigability, and exertional dyspnea. Splenomegaly
is often present at the time of diagnosis; hepatomegaly is
less common; and lymphadenopathy is relatively uncom-
mon. Persons in the early chronic phase of CML gener-
ally are asymptomatic, but without effective treatment
most will enter the accelerated phase within 4 years.
The accelerated phase of CML is characterized by
enlargement of the spleen and progressive symptoms.
Splenomegaly often causes a feeling of abdominal full-
ness and discomfort. An increase in basophil count and
more immature cells in the blood or bone marrow con-
firm transformation to the accelerated phase. During
this phase, constitutional symptoms such as low-grade
fever, night sweats, bone pain, and weight loss develop
because of rapid proliferation and hypermetabolism of
the leukemic cells. Bleeding and easy bruising may arise
from dysfunctional platelets. Generally, the accelerated
phase is short (6 to 12 months).
The terminal blast crisis phase of CML represents
evolution to acute leukemia and is characterized by an
increasing number of myeloid precursors, especially blast
cells, in the blood (Fig. 11-7). Constitutional symptoms
become more pronounced during this period, and sple-
nomegaly may increase significantly. Isolated infiltrates
of leukemic cells can involve the skin, lymph nodes,
bones, and CNS. With very high blast counts (>100,000
cells/
μ
L), symptoms of leukostasis may occur. The prog-
nosis for patients who are in the blast crisis phase is
poor, with a median survival of 3 months.
Adiagnostic feature of CML is an elevatedwhite blood
count, with a median count of 150,000/
μ
L at the time
of diagnosis, although in some cases it is only modestly
increased. The hallmark of the disease is the presence of
the BCR–ABL gene product, which can be detected in
the peripheral blood. The treatment of CML is evolving
rapidly. An inhibitor of the BCR–ABL tyrosine kinase,
imatinib mesylate, induces complete remission in a high
fraction of persons with stable-phase CML.
33,34
The only
available curative treatment for CML is allogeneic bone
marrow or stem cell transplantation.
Malignant Lymphomas
The lymphomas are a diverse group of solid tumors
composed of neoplastic lymphoid cells that vary with
respect to molecular features, genetics, clinical presen-
tation, and treatment. Two groups of lymphomas are
recognized: non-Hodgkin lymphomas (NHLs) and
Hodgkin lymphoma (HL).
4,7,39
Non-Hodgkin Lymphomas
The NHLs are one of the most common cancers in the
United States, accounting for about 4% of all cancers.
The average American has a risk of developing NHL
during his or her lifetime of about 1 in 50. Personal
risk factors that may affect the incidence level include
gender, ethnicity, chemical or radiation exposure, and
immune dysfunction.
40
Although some NHLs are com-
mon in children, more than 95% of cases occur in
adults.
40
More than half of the people who develop
NHLs are over age 65.
40
As with most other malignancies, the cause of NHLs is
largely unknown. However, impairment of the immune
system and infectious agents may play a role. There is
evidence of EBV infection in essentially all people with
Burkitt lymphoma, which is endemic to some parts of
Africa.
4,7
A second virus, the human T-cell lymphotropic
virus (HTLV-1), which is endemic in the southwestern
islands of Japan, has been associated with adult T-cell
leukemia/lymphoma. The NHLs are also seen with
increased frequency in persons infected with HIV, in
those who have received chronic immunosuppressive
therapy after organ transplantation, and in individu-
als with acquired or congenital immunodeficiencies.
40
There is also a reported association between chronic
Helicobacter pylori
infection and low-grade MALT lym-
phoma of the stomach.
Non-Hodgkin lymphomas can originate from malig-
nant transformation of either the T or B cells during
their differentiation in the peripheral lymphoid tis-
sues.
4,7
Although the NHLs can originate in any of the
lymphoid tissues, they most commonly originate in the
lymph nodes. Like normal lymphocytes, transformed
B and T cells tend to home into particular lymph node
sites, leading to characteristic patterns of involvement.
For example, B-cell lymphomas tend to proliferate
in the B-cell areas of the lymph node, whereas T-cell
lymphomas typically grow in the paracortical T-cell
areas
4,7
(see Fig. 11-4). All have the potential to spread
FIGURE 11-7.
Peripheral blood showing blast crisis in chronic
myelogenous leukemia. (From the Centers for Disease Control
and Prevention Public Health Image Library. No. 6. Courtesy of
Stacy Howard.)
