CRITERIA

Incidence/ Mortality

Etiology/Risk Factors

Diagnosis & Detection

TYPES OF LEUKEMIA Acute Chronic Chronic Myelocytic Lymphocytic Myelocytic Leukemia Leukemia Leukemia 15 39 y/o >50 >50 Equal Male Male incidence Caucasian in both sex Ionizing radiation Chemicals and drugs Marrow hypoplasia Environmental interactions Genetic factors Viral factors Immunologic factors Interactive factors Anamnesis (detailed medical review of past health state): One of the first steps in establishing a leukemia diagnosis is a detailed and complex medical review of a patient's past health problems and general health state, family medical history, leukemia risk factors, and symptoms. Acute Lymphocytic Leukemia < 15 y/o Male Caucasian Physical examination During a physical examination, the doctor looks for changes to the internal organs like swelling of the liver, spleen, or lymph nodes from the neck, underarms, and groin area. Laboratory Tests

Blood test: A blood test allows the pathologist to examine the blood cells under a microscope. The examination criteria are: (1) the blood cells' general appearance, (2) the number of each type of blood cells

(red and white cells, and platelets), (3) the cell maturation stage, and (4) the presence or absence of leukemia blast cells. Blood tests are also conducted to diagnose and establish the type of leukemia. Bone marrow test: This test allows the pathologist to examine the marrow cells. It usually confirms the presence or absence of leukemia and the leukemia type. The bone marrow sample can be collected in two ways: (1) through a bone marrow aspiration - the bone marrow sample is removed with a thin needle inserted into the marrow of a large bone, and (2) through biopsy - the bone marrow sample is removed together with the bone tissue. Spinal tap: This test allows the pathologist to examine the cerebrospinal fluid (the fluid located in and around the brain and spinal cord), and to confirm the presence of leukemia cells. A cerebrospinal fluid sample is removed through a lumbar puncture. A thin needle is inserted into the space around the spinal cord and removes a sample of fluid. This test is performed only when the leukemia diagnosis was confirmed with the purpose of establishing whether or not the leukemia cells had spread to other internal organs. Immunophenotyping: An immunopheno type test helps identify the chemicals located on the cells' surface and diagnose the disease by placing various sorts of strain on bone marrow, blood, or lymph nodes cells. For leukemia, the pathologist uses antigens (proteins) and the bodys antibodies. The antibodies react to certain antigens. This test helps in identifying leukemia cells (if present), the type of leukemia cells (lymphocytic or myelogenous cells), and the cell subtype, which helps establish a treatment approach. Cytogenetics or chromosome analysis. This test analyzes the shape and number of the chromosomes from the leukemia cell, and can identify the chromosome alteration and sometimes the gene mutation. The advantages of this test are: (1) it identifies the specific leukemia type involved, (2) it helps with establishing an effective treatment plan,

and (3) it allows follow-up evaluations of the treatment effectiveness. Imaging Techniques The purpose of these techniques is to locate masses of leukemia cells inside the body. Some of the most used imaging techniques are:

Chest X-rays: An x-ray test uses high energy electromagnetic radiation to penetrate the body and create an image of the body's interior on film. An x-ray can reveal any possible mass of leukemia cells in the chest. Ultrasounds: Ultrasound imaging is a medical technique that uses high-frequency sound waves to create an interior image of the body on a special computer screen. This image is formed from the echoes of the sound waves on the surface of the organs. Abnormal tissue masses and organs reflect sound waves differently. This test involves a device called a transducer that is placed on the upper part of the abdomen, and a computer that translates this sound into an image. Ultrasound imaging is a safe, noninvasive and fast test that can detect leukemia cell masses. Usually, ultrasounds are used to detect whether or not the liver, kidneys, or the spleen were invaded by the leukemia cells. Bone or Gallium Scan: This is usually used to detect whether or not the bone pain (a symptom of leukemia) is caused by a tumor. This type of bone scan uses a radioactive form of gallium which collects in the areas where there are leukemia cells or infections. Computed Tomography (CT): This imaging test is similar with an xray test, and creates a detailed cross-sectional image of the body.

A CT scan is usually performed in two steps for a better diagnosis outcome: 1). First, the targeted area is scanned without a contrast agent. 2). Second, the targeted area is scanned after a contrast agent was

administrated, and the two are compared.

Magnetic Resonance Imaging (MRI): This imaging technique uses radio waves and strong magnets to reveal a complete image of the body targeted area. The energy from the radio waves is absorbed by the tissues and then revealed into a recognizable pattern on a special monitor.

Diagnostic findings

Low RBC count, Hb, Hct; low platelet count; low,normal,or high WBC count; transverse lines of rarefaction at ends of metaphysic of long bones on xray; hypercellular bone marrow with lymphoblasts; lymphoblasts also possible in cerebrospinal fluid

Low RBC count, Hb, Hct; low platelet count; low to high WBC count, with myeloblasts; greatly hypercellular bone marrow with myeloblasts

Mild anemia, and thrombocytopenia with disease progression; total WBC count > 100,000/l; increased in peripheral lymphocytes; increased in presence of lymphocytes in bone marrow;

Clinical features

Fever; pallor; anorexia, fatigue and weakness;

Fatigue and weakness, headache,

No symptoms usually, detection of disease often

Low RBC count, Hb, Hct; high platelet count early, lower count later; increased in polymorphonucle ar neutrophils, normal number of lymphocytes and normal of low number of monocytes in WBC differential; low leukocyte alkaline phophatase; presence of Philadelphia chromosome in 90% of patients No symptoms early in disease; fatigue and

Diagnosis and staging

bone, joint and abdominal pain; generalized lympadenopathy; infections; weight loss; hepatosplenomeg aly; headache; mouthsores; neurologic manifestation including CNS involvement, increased intracranial pressure secondary to meningeal infiltration Childhood Acute Lymphocytic Leukemia Risk Groups

mouthsores, minimal hepatosplenomeg aly, and lympadenopathy; anemia, bleeding, fever, infection, sterna tenderness

during examination for unrelated condition, chronic fatigue, anorexia, splenomegaly, and lymphadenopathy , hepatomegaly

weakness, fever, sternal tenderness, weight loss, joint pain, bone pain, massive splenomegaly, increased in sweating

Phases 1. Untreated: In this phase, leukemia has just been diagnosed 1. Standard (low) and the treatment has focused only risk: Includes children between to relieve symptoms like one and nine fever, pain, and years old with a bleeding. The white blood cells main count less than characteristics of 50,000/m L at this phase are: 1) diagnosis.

Rai Classification Stage 0 lymphocytosis only (> 15,000/mm3) Stage I lymphocytosis and adenopathy Stage II lymphocytosis and anemia (hemoglobin < 11g/dl) Stage IV

1. Chronic stage: In this stage, less then 10 percent of the blood and bone marrow cells are blasts, and the patient displays relatively mild symptoms. Patients during this stage respond well to standard

2. High risk: Includes children younger than one year or older than nine with a white blood cells count of 50,000/m L or more at diagnosis. 3.Recurrent: Ref ers to the leukemia that has recurred (relapsed, came back) after it was treated.

Adult Acute Lymphocytic Leukemia Phases 1. Untreated adult ALL: In this phase, leukemia has been diagnosed and the treatment focuses only on symptoms (fever,

more than 20 lymphocytosis percent of the and bone marrow thrombocytopeni cells are leukemia a (platelets < cells, and 2) 100, 000/mm3) some leukemia Binet signs and Classification symptoms are present. Stage A lymphocytosis 2. Remission: In and enlargement this phase, of three lymph leukemia has node group been treated. The Stage B main lymphocytosis characteristics of and enlargement this phase are: 1) of > three lymph less than 5 node groups percent of the Stage C bone marrow lymphocytosis cells are leukemia with anemia and cells, and 2) there thrombocytopeni are no more signs a and symptoms of leukemia. 3. Recurrent: In this phase, leukemia has recurred (relapsed, came back) after it was

treatment. 2. Accelerated stage: In this stage, between 10 and 30 percent of the blood and bone marrow cells are blast cells, and the patient displays several symptoms like fever, poor appetite, and weight loss. Patients during this stage do not respond as well to the treatment as in the chronic stage. 3. Blastic stage: In this stage, more than 30 percent of the blood and bone marrow cells are blast cells, and the blast cells often spread to the bones and

bleeding, and pain) relief. The main characteristics of this phase are: 1) more then 5 percent of the cells in the bone marrow are leukemia cells, and 2) signs and symptoms of leukemia are present. 2. Adult ALL in remission: In this phase, leukemia has been treated. The main characteristics of this phase are: 1) less than 5 percent of the cells in the bone marrow are leukemia cells, and 2) there are no more signs and symptoms of leukemia present in the brain and spinal cord, or

treated.

tissues adjacent to the bone marrow. 4. Relapse: This stage occurs after the remission (leukemia relapses), and is characterized by an increased number of blast cells.

other organs of the body. 3. Recurrent adult ALL: In this phase, leukemia has been recurred (relapsed, came back) after it was treated. Metastasis location Survival Prognosis is poorer for adults than for children Prognosis is better than in AML Curable in children Combined chemotherapy, radiotherapy, and immunotherapy; drugs: vincristine, prednisone, Lasparaginase Brain Spinal cord Prognosis is generally poor. Best prognosis with bone marrow transplant Prognosis is poor. Prognosis is generally poor.

Treatment modalities

Chemotherapy with daunorubicin, cytarabine, doxorubicin, 6thioguanine; bone marrow and stem cell transplant

Chemotherapy with alkylating agents (chlorambucil) and glucocorticoids (only when symptoms appear)

Chemotherapy with agents used in AML; also vincristine and busulfan; bone marrow and stem cell transplant