-IBIS-1.5.0-
tx
immune system
leukemia
diagnoses

definition and etiology

definition:
A heterogenous group of neoplasms developing in the the bone marrow and causing malignant changes in the hematopoietic cells.

etiology:
There are several types of leukemia, and each type is dependent upon age, sex, race, and site. Although associated microorganisms are identified in only a minority of patients, there are known risk factors: ionizing radiation (iatrogenic or other); chemicals and drugs (benzene, arsenic, phenylbutazone, chloramphenicol, chemotherapeutic agents); marrow hypoplasia; genetic factors (Down's syndrome, Klinefelter's syndrome, Fanconi's aplasia); viral agents (RNA viruses); immunologic factors (immunodeficiency). A multiplicity of causes may be factors in each individual.

There are 4 basic types of leukemia:
acute lymphocytic leukemia (ALL)
acute myelocytic leukemia (AML)
chronic lymphocytic leukemia (CLL)
chronic myelocytic leukemia (CML)

signs and symptoms

By the different leukemias:

• ALL: Primarily seen in children. In half the patients the lymphocyte concentration is high; in half it is normal or low. There are many lymphoblasts, severe anemia, and low platelets. Lymphadenopathy is often present and the majority of patients have splenomegaly. CNS involvement occurs in 50% of patients after a year. WBC is rarely > 100,000/mm3. Normoblasts and polychromatophilia are common. Blast cells are present in bone marrow even if none show in peripheral smear.

• AML: This type can occur at any age. The lymphocyte concentration is high in 60% of patients and normal or low in the other 40%. There are many myeloblasts and the anemia is usually severe. Most patients have a decreased platelet count. Lymphadenopathy is occasionally present and half of the patients will have splenomegaly. LDH increased; occasionally slight increase in AST, ALT.

Acute leukemia has an abrupt onset that appears infectious in nature. There is often a high fever and joint pains. Bleeding is common. However, the acute leukemias may also have an insidious onset with only increasing weakness and pallor. May see meningeal leukemia in 25-50% of children. Infection causes 90% of deaths.

• CML: This predominately strikes young adults and the lymphocyte concentration is always high. The differential uncovers the entire myeloid series. Most patients have anemia, progressively severe, normocytic and normochromic. 60% of patients have low platelets (terminal stages) and others may be normal or increased in early stages. Lymphadenopathy is uncommon but most patients suffer from severe splenomegaly. This type of leukemia is associated with the presence of the Philadelphia chromosome. Increased WBC count is the earliest sign, with progressive shift to left. Lymphocytes show relative decrease. WBC count is usually 100-500,000 /mm3 at onset. There may also be increased LDH, uric acid, AST, ALT, B12, and hyperplastic bone marrow.

• CLL: This form of leukemia is usually seen from middle age into old age. The lymphocyte concentration is almost always high, and the differential shows 90% identical small lymphocytes. Anemia affects only 50% of patients, and it is typically mild, becoming more severe over time. Platelets will be low in 20-30% of patients and lymphadenopathy is frequently present, as well as splenomegaly. WBC count 50-250,000/mm3, with blast forms uncommon; autoimmune hemolytic anemia in 25%; bone marrow hyperplastic; less elevation in serum enzymes than in CML.

Patients with chronic leukemias usually present with nonspecific symptoms: fatigue, weight loss, weakness. Diagnosis can follow careful work-up or a routine blood draw.

course and prognosis

In untreated acute leukemia patients, death is inevitable and frequently very quick. Death is usually from hemorrhage or secondary infection. On chemotherapeutic drugs, the median age for a child to survive is 36 months, and if the child survives past that, may become cured.

In CML the prognosis is unfavorable: the disease progresses gradually leading to death usually within 3-4 years. 20% survive longer than 5 years, and 2% survive longer than 10 years. Once "blastic transformation" occurs, the patient typically has only from 4-6 months to live. Conventional treatment is administration of chemotherapeutic drugs.

In CLL, the disease is progressive, although some patients will be asymptomatic for years and may experience lengthy remissions with treatment. However, gradually the disease becomes more active, and the patient succumbs.

differential diagnosis

• other causes of lymphadenopathy, anemia, lymphocytosis


footnotes