The Leukemias

The Leukemias



Jennifer K. Simpson



Acute Lymphocytic Leukemia



DEFINITION


Leukemias are malignant neoplasms characterized by abnormal proliferation and development of leukocytes and their precursors, which infiltrate the bone marrow, peripheral blood, and other organs resulting in altered normal cell differentiation. Leukemias are classified according to cell type (lymphoid or myeloid) and can be acute or chronic. Acute leukemias are characterized by a block in differentiation resulting in massive accumulation of immature cells or blasts; onset is acute. Acute lymphocytic leukemia (ALL) is a cancer of lymphoblasts. ALL can be divided into two subtypes. The majority of ALL patients, 85%, have B-cell subtype and 15% of patients are diagnosed with T-cell subtype.



INCIDENCE




• In the United States, a total of 5,200 new cases of ALL are estimated for 2007 with 1,420 deaths.


• Most common form of leukemia in children <19 years of age


• >30% of new cases of ALL are in children


• Incidence in 1- to 4-year-old children is more than nine times the rate for young adults aged 20 to 24 years.


• Male > female


• Whites >African Americans



ETIOLOGY AND RISK FACTORS




• Radiation exposure linked with development of ALL, although only found in Japanese atomic bomb survivors


• Congenital diseases are linked with ALL: Down syndrome


• Cytogenetic abnormalities—possible involvement of oncogenes


• Prior treatment with intensive immunosuppressive therapies



SIGNS AND SYMPTOMS




• Generally abrupt presentation


˚ Malaise

˚ Fatigue

˚ Bony pain—especially sternal

˚ Sweats

˚ Bleeding; easy bruising

• Physical findings


˚ Pallor

˚ Petechiae

˚ Ecchymoses

˚ Lymphadenopathy

˚ Splenomegaly

˚ Hepatomegaly

˚ Mediastinal mass generally with T-cell subtype

˚ Abdominal adenopathy with Burkitt’s type


DIAGNOSTIC WORKUP




• Medical history and physical examination


• Laboratory tests


˚ Complete blood cell count with differential

image Pancytopenia as a result of marrow replacement by tumor

image Two thirds of patients have white blood cell count >100,000

image 10% will have normal white blood cell count

• Serum chemistry panel:


˚ Elevated lactate dehydrogenase, uric acid correlates with large tumor burden

• Cytogenetic analysis:


˚ Permits identification of chromosomes or gene abnormalities in the cells

˚ t(9;22) Philadelphia (Ph) chromosome most common abnormality in adult ALL (17%-25% of cases)

• Immunophenotyping:


˚ Enables the physician to determine the type of disease that is present in the patient

• Bone marrow aspirate/biopsy


• Lumbar puncture—to identify malignant cells in the cerebrospinal fluid


• Chest x-ray film



CLINICAL STAGING


No clinical staging is performed for ALL.



TREATMENT


Average length of treatment varies between 1.5 and 3 years. There are three phases to the treatment of ALL:



• Remission induction – typically requires hospitalization for approximately 4 weeks:


˚ Common agents include:

image Prednisone

image Vincristine

image Anthracycline

image Asparaginase

image Cyclophosphamide

image Etoposide

image Methotrexate

image Cytarabine

image Imatinib (if Ph +)

˚ Complete response rates range from 60% to 90% with these induction regimens.

• Consolidation or intensification


˚ Patients must be in remission to begin this phase.

˚ Typically lasts 1-3 months

˚ Treatment is still fairly intense and many of the same agents administered during induction are utilized.

˚ High risk patients may be considered for transplant at this time. This includes:

image Allogeneic stem cell transplant

image Autologous stem cell transplant

• Maintenance


˚ Lasts approximately 2 years

˚ Typical agents include:

image Methotrexate

image 6-mercaptopurine (6-MP)

image Vincristine

image Prednisone

• Central nervous system prophylaxis


˚ Typically completed during the induction phase but may extend throughout therapy

˚ Common agents include:

image Methotrexate

image Hydrocortisone

image Cytarabine

image Cranial/spinal irradiation

image High dose IV methotrexate

• Patients who have relapsed after induction chemotherapy or maintenance therapy are unlikely to be cured by further chemo-therapy alone.


˚ Reinduction chemotherapy followed by allogeneic bone marrow transplantation should be considered.

˚ Patients who do not have an HLA-matched donor may be considered for an unrelated stem cell/bone marrow transplant

˚ Clinical trials should also be considered


PROGNOSIS




• Overall 5-year survival:


˚ Adults 64%

˚ Children 85%

• Long-term follow-up of 30 patients with ALL in remission for at least 10 years has demonstrated 10 cases of secondary malignancies.


• Of 31 long-term female survivors of ALL or acute myeloid leukemia under 40 years of age, 26 resumed normal menstruation after completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred.



PREVENTION


There are no known preventive measures for ALL.



BIBLIOGRAPHY



American Cancer Society. Leukemia—acute lymphocytic. Retrieved June. 11, 2007, from http://www.cancer.org/docroot/lrn/lrn_0.asp, 2007.


Jemal A., Murray T., Ward E., et al. Cancer statistics, 2005. CA: A Cancer Journal for Clinicians. 2005;55:10–30.


Leukemia and Lymphoma Society. Acute lymphocytic leukemia. Retrieved June. 11, 2007, from http://www.leukemia-lymphoma.org/all_page?item_id=7049, 2007.


National Cancer Institute. Adult acute lymphoblastic leukemia (PDQ). Retrieved June. 11, 2007, from http://www.cancer.gov/cancertopics/pdq/treatment/adultALL/HealthProfessional/page1#Reference1.19, 2007.


Micallef I.N., Rohatiner A.Z., Carter M., et al. Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. British Journal of Haematology. 2001;113:443–445.



Acute Myelogenous Leukemia



DEFINITION


Acute myelogenous leukemia (AML) is a cancer of the blood and bone marrow specifically involving the myeloid progenitor cells. Most AML is distinguished from other related blood disorders such as myelodysplastic syndrome by the presence of more than 20% blasts in the blood and bone marrow. AML results from the failure of the myeloid progenitor cells to mature. The mechanism causing the arrest of cell maturation is not fully understood; however, it may often involve the activation of abnormal genes through chromosomal translocations and other genetic abnormalities. This developmental arrest results in a marked decrease in the production of normal blood cells, resulting in varying degrees of anemia, thrombocytopenia, and neutropenia. Second, the immature cells (blasts) begin to accumulate in the blood, bone marrow, and frequently the liver and spleen as a result of their rapid proliferation and reduction in apoptosis (programmed cell death).



INCIDENCE




• In the United States, a total of 13,410 new cases of AML are expected in 2007, with more than 90% of the cases diagnosed in adults.


• 8,990 deaths from the disease are estimated for 2007 in the U.S.


• Affects all age groups with median age at diagnosis of 65 years. There is an increased prevalence with age.


• More common in whites


• More common in men than women, particularly in older patients



ETIOLOGY AND RISK FACTORS


The specific etiology or cause of AML is unknown. Of all leukemias, AML has the strongest link to an increased risk seen in patients who have had prior radiation and toxin exposure.



• The most common risk factor is the presence of an antecedent hematologic disorder, usually high-risk myelodysplastic syndrome.


• Radiation exposure: increased risk seen in patients exposed to atomic bomb explosion in Japan; early radiologists (before appropriate shielding); and patients irradiated for ankylosing spondylitis


• Prior chemotherapy, particularly alkylating agents and topoisomerase II inhibitors


• Period between drug or radiation exposure and evidence of acute leukemia approximately 3 to 5 years for alkylating agents or radiation exposure but only 9 to 12 months for topoisomerase II inhibitors


• Tobacco use: It is estimated that one fifth of cases of AML are related to smoking.


• Congenital disorders resulting in development of AML during childhood, although some may develop as adults


˚ Bloom syndrome, Down syndrome, congenital neutropenia, Fanconi anemia, and neurofibromatosis

• Increased risk with age: risk increases tenfold between 30 and 70 years of age



SIGNS AND SYMPTOMS


Presenting symptoms are related to bone marrow failure with resulting anemia, neutropenia, and thrombocytopenia or organ infiltration with leukemic cells. Common sites include the spleen, liver, and gums. Organ infiltration occurs most commonly in patients with monocytic subtypes.



Patient Complaints




• Fatigue


• Weakness


• Shortness of breath


• Weight loss


• Fever


• Bleeding and easy bruising


• Early satiety and fullness in right upper quadrant (from splenomegaly)


• Bone pain resulting from high leukemic cell burden and increased pressure in the marrow


• Respiratory distress and altered mental status from leukostasis, which is a medical emergency and requires immediate treatment



Physical Findings




• Pallor


• Petechiae or ecchymoses


• Hepatosplenomegaly


• Signs of infection, including pneumonia


• Gingivitis


• Rash resulting from skin infiltration



DIAGNOSTIC WORKUP




• Medical history and physical examination


• Laboratory tests:


˚ Complete blood cell count with differential

˚ Serum chemistry panel

˚ Elevated lactate dehydrogenase, uric acid: correlates with large tumor burden

˚ Cytogenetics

image Permits identification of chromosomes or gene abnormalities in the cells

• Additional studies:


˚ Bone marrow aspirate/biopsy

˚ Immunophenotyping

image Helps determine the type of disease that is present in the patient through identification of antigens (proteins) on the cell surface and the antibodies produced by the body that match the antigen

• Imaging studies


˚ Chest x-ray film


CLINICAL STAGING


Clinical staging is not done in AML.



HISTOLOGY


Determination of the subtype of AML helps to predict prognosis and suggest treatment implications. However, for all practical purposes the treatment is similar for all subtypes. Classification of AML has been revised under the auspices of the World Health Organization (WHO) and replaces the older French American British (FAB) classification. The WHO classification for AML incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunological markers in an attempt to construct a classification that is universally applicable and prognostically valid. Elements of the FAB classification that were specific to disease morphology have been retained. The WHO classification is outlined in the box below.

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Mar 1, 2017 | Posted by in NURSING | Comments Off on The Leukemias

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