Leukemia



Leukemia


Aiko M. Kodaira



I. Definition

A. Leukemia accounts for about 4% of all new cancer cases in the United States and is generally perceived as a fatal disease (Jemal et al., 2003). Leukemia is a group of hematopoietic malignancies characterized by both quantitative and qualitative alteration in circulating leukocytes affecting the bone marrow and lymphatic system. It is believed that leukemia may be caused by the arrest of one or more of the following normal cell functions: cell differentiation (maturation), proliferation (reproduction), and/or apoptosis (programmed natural cell death). Leukemia is a malignant disease associated with diffuse abnormal and uncontrolled proliferation of immature leukocyte precursors in the bone marrow. The malignant cell replaces normal elements in all areas of hematopoietic bone marrow. Leukemia is described by a particular cell type of origin. Most types originate in the white blood cell lines, but leukemia can also begin in the erythroid (red blood) or megakaryoid (platelet) cell line. Leukemias are classified by the extent of differentiation or by the maturity of the cells. The acute leukemias are minimally or poorly differentiated and are characterized by the presence of immature cells called blasts. The chronic leukemias show a greater degree of differentiation or maturation. An overview of the common subtypes of leukemia, classifications, and characteristics is included in Table 16-1. Some institutions use the French-American-British (FAB) classification system for acute leukemia. This is presented in Figure 16-1.

B. Different types of leukemia affect different age groups. The majority of acute lymphocytic leukemia (ALL) cases are seen in children, whereas chronic lymphocytic leukemia (CLL) is typically a disease of the elderly. Remissions are often obtained with current therapies; however, relapse is common and probable, especially in adults. The two most common causes of death in leukemic patients are infection and bleeding. The accumulation of dysfunctional cells limits available nutrients and space in the bone marrow. This restricts the production of normal hematopoietic cells and their ability to differentiate, mature, and function normally. Failure to manage the consequences of this loss of functional leukocytes, red blood cells, and platelets often results in death. The etiology of leukemia remains unclear; however, recent advances in molecular genetic analysis have provided critical insights into the nature of leukemia. Although there are still many questions to be
answered, there is no doubt that molecular genetic analysis will change the future of leukemia treatment.


II. Etiology:

The definitive etiology of leukemia is unknown, although a number of causative factors have been identified.

A. Immune Response Factors

1. The first theory is the immune competence theory, which states that having any immune deficiency predisposes a person to a hematologic malignancy. This is supported by an increased incidence of leukemia after solid organ transplantation.

2. A second theory is that genetic predisposition abnormalities may cause leukemia. There is an increased incidence of acute leukemia in children with Down syndrome and Fanconi’s anemia. Additionally, people with a family member diagnosed with leukemia have four- to sevenfold increased risk for leukemia (Yarbro, Frogge, Goodman & Groenwald, 2000).

3. The viral theory links some viruses to the development of leukemia. The most significant supporting factor is the human T-cell leukemia virus (HTLV-I) associated with adult T-cell leukemia in Japan and the Caribbean. HTLV-II is associated with a rare form of hairy cell leukemia and is prevalent in intravenous drug abusers.

B. Risk Factors: Two clear risk factors exist for the development of leukemia, especially the acute form.

1. Exposure to ionizing radiation (survivors of the atomic bomb or nuclear accidents have an increased incidence of acute leukemia).

2. Exposure to known cytotoxic chemicals (cytotoxic drugs are often used to treat other malignancies or autoimmune diseases). Acute myelogenous leukemia (AML) is the most frequently reported treatment-related secondary cancer.


III. Patient Management

A. Assessment: The following are signs and symptoms of leukemia:

1. Granulocytopenia-related symptoms: Fevers, persistent infections (common sites are lung and sinus, urinary tract, abdomen, oral cavity, and perirectal area), prolonged wound healing. These symptoms often indicate malignant changes in both quality and quantity of leukocytes.

2. Thrombocytopenia-related symptoms: Petechiae, rashes, easy bruising, bleeding gums, epistaxis, hemoptysis. Uncontrolled bleeding or intracranial bleeding may occur secondary to disseminated intravascular coagulation (DIC), a common complication associated with acute promyelocytic leukemia (APL or M3 AML).

3. Anemia-related symptoms: Fatigue, malaise, and decreased tolerance for exercise or activities of daily living (ADL), pallor, dyspnea, chest pain, cold intolerance.

4. Leukemia infiltrate-related symptoms: Splenomegaly, lymphadenopathy, pain or swelling in bones and joints, inflammation of the gums. In severe cases, renal failure or respiratory distress may be observed. Headache, mental status change, nausea and vomiting, and cranial nerve palsies are occasionally exhibited as signs of central nervous system (CNS) infiltration by leukemia cells and most frequently occur in patients with ALL.










TABLE 16-1 Leukemia Overview






























































Leukemia Type (FAB classification)

Defining Characteristics

Prognosis


Acute nonlymphocytic leukemia

Cell maturation arrested along the myeloid cell line

Prognosis of leukemia is highly dependent on the type of cytogenetic abnormality involved.
Cytogenetic abnormalities are divided into three groups: normal, favorable, and poor.


Acute leukemia—minimally differentiated (M0 AML)
Acute leukemia—undifferentiated myelocytic (M1 AML)
Acute myelocytic leukemia AML (M2 AML)

Age at onset: 18-25 years and 45-60 years, low to high WBC count at presentation. Splenomegaly, hepatomegaly, and lymphadenopathy are usually not seen.

No abnormality, +8, 11q23, +21, del(9q) are normal t(8;21), inv(16) are favorable, and complex, −7, −5 are poor. M4 and M5 AML often involve MLL gene (11 gene) abnormalities, such as t(11;17)(q23;q21) or t(6;11)(q27;q23). 65% to 80% achieve remission with therapy, relapse is common. Median survival with treatment is 10-15 months.


Acute myelomonocytic leukemia AM ML (M4 AML)
Acute monocytic leukemia AMoL (M5 AML)

Often high WBC at presentation, with organ infiltration, such as gum hypertrophy, cutaneous leukemia, splenomegaly, hepatomegaly and lymphadenopathy. High incidence of central nervous system (CNS) involvement.


Erythroleukemia EL (M6 AML)

Complicated diagnosis, hard to distinguish from MDS, poor response to chemotherapy

Poor prognosis


Megakaryocytic leukemia (M7 AML)

Extremely rare type of AML. Large organs (liver, spleen), accumulation of sclerotic tissue in bone marrow

Poor prognosis


Acute promyelocytic leukemia APL (M3 AML)

Normal to moderately high WBC at presentation, high risk for DIC

APL with t(5;17) with PML/RARα fusion protein is highly responsive to ATRA therapy and approximately 85% of patients achieve complete remission.


Acute lymphocytic leukemia


Erythroleukemia EL (M6 AML)

Cell maturation arrested along the lymphoid cell line

T-cell disease has a favorable prognosis


Childhood acute lymphocytic leukemia (L1 ALL)

Leukemia is most common form of cancer in children, and 75% of those are ALL. Age of onset: 2-3 years.
Splenomegaly, hepatomegaly, lymphadenopathy, CNS involvement are prevalent.

Patient with t(9;22), t(1;19), infant with t(4;11), high WBC count, age <1 year or >10 years, CNS involvement, and longer time to achieve remission are associated with poor prognosis.


Adult acute lymphocytic leukemia (L2 ALL)

Philadelphia chromosome (t(9;22)) is the most common cytogenetics abnormality in adults. Splenomegaly, hepatomegaly, lymphadenopathy, CNS involvement are prevalent.

Poorer prognosis than childhood ALL. Poor prognosis with t(9;22) involving 11q23 and t(1;19). Age >50 years, high WBC, longer time to achieve remission are associated with poorer prognosis.


Burkitt’s type leukemia (L3 ALL)

Age at onset: after 65 years, mature B-cell ALL, high CNS involvement and high tumor burden, high risk for TLS, rapid clinical course

Worst prognosis in ALL, involve t(8;14)(q24;q11). High LDH associated with poor prognosis.


Chronic myelocytic leukemia (CML)

7% to 15% of adult leukemia, median age at onset 45-55 years, 90% of patients have + Philadelphia chromosome (t(9;22)), characterized by a chronic phase followed by an accelerating and blastic phase.

Treatment is most effective in chronic phase. Accelerating and blastic phases are often refractory to treatment. 3 years of median survival with treatment.


Chronic lymphocytic lymphoma (CLL)

Age at onset: after 60 years, most common type of leukemia in adults, may be familial, prone to viral infection, patients with low-risk CLL often do not require treatment for many years.

4-6 years of median survival rate. Low-risk patients mostly die of other causes, whereas the high-risk CLL patients die from disease-related complications within a few months of diagnosis.








Figure 16-1. Hematopoietic cascade and FAB classification.


B. Diagnostic Parameters

1. Laboratory tests

a. Complete blood count (CBC) reflects anemia, thrombocytopenia, and neutropenia.

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Sep 16, 2016 | Posted by in NURSING | Comments Off on Leukemia

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