Porth's Essentials of Pathophysiology, 4e

253

Disorders of White Blood Cells and Lymphoid Tissues

C h a p t e r 1 1

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.)