Leukemia+(ALL,+AML,+CML)

Acute Myelogenous Leukemia: seen in patients over 40, median age at diagnosis is 65. Slightly higher incidence in males. [3] Chronic Lymphocytic Leukemia: 30% of all leukemia cases in US. Median age at diagnosis is 71, rarely seen in patient younger than 40. Males are twice as likely than females to develop CLL. [3] Chronic Myelogenous Leukemia: Most commonly seen in patients in their 40s, rare before the age of 20. Slightly higher incidence in males. [3] || AML: exposure to radiation, Fanconi’s anemia and Bloom syndrome, exposure to benzene and alkylating agents. [3] CLL: hereditary causes, immunodeficiency syndrome and viruses. [3] CML: radiation and benzene exposure are associated. [3] || AML: nonspecific flu-like symptoms, anemia, reduced platelet production, neurtopenia, enlarged spleen. [3] CLL: patients are commonly symptom-free at diagnosis, caught as an incidental finding from routine blood tests. Fatigue, fever, night sweats and weight loss may be present. Enlarged spleen and lymphadenopathy are common. [3] CML: fatigue, heat intolerance, sweating, weight loss, easy bruising, abdominal discomfort, enlarged spleen, hepatomegaly and lymphadenopathy. [3] ||
 * **Epidemiolgy:** || Acute Lymphoblastic Leukemia: most common pediatric leukemia, most commonly seen in children 2-10 years old, rarely seen in patients over 14. Higher incidence in males than females. [3]
 * **Etiology:** || ALL: exposure to radiation, genetic predisposition, Human T-cell lymphotropic virus type 1 in adults. [3]
 * **Signs & Symptoms:** || ALL: nonspecific, flu-like symptoms, anemia, thrombocytopenia, and neutropenia, liver, splenic and testicular enlargement, joint swelling, bone pain and tenderness. [3]
 * **Diagnostic Procedures:** || The initial diagnostic workup includes a complete medical history and a comprehensive physical examination. Leukemia is typical detected by a complete blood cell count and bone marrow examinations. However, diagnostic procedures are varied by its classification.

Acute Lymphocytic Leukemia (ALL) A complete blood cell counts and bone marrow biopsy including flow cytometry and cytogenetic studies.

Acute Myelogenous Leukemia (AML) Specific blood tests including complete blood counts, differential leukocyte, platelet counts, and blood smears. A bone marrow aspiration and biopsy detecting auer rods.

Chronic Myelogenous Leukemia (CML) Diagnosis of CML is difficult. Specific blood tests include complete blood counts, differential leukocyte, and platelet counts revealing abnormality may indicate CML. Presence of the Philadelphia chromosome is the main indicator of CML. [4] || ALLis a B-cell that is expressed by alack of definitive myeloid differentiation. Most of cases show widespread replacement of marrow by neoplastic lymphoblasts with decrease of normal hematopoietic elements.
 * **Histology:** || Acute Lymphocytic Leukemia (ALL)

Acute Myelogenous Leukemia (AML) AML is characterized by having a large population of larger myeloblasts with prominent nucleoli and fine nuclear chromatin. Also, increased numbers of mature eosinophils are seen.

Chronic Myelogenous Leukemia (CML)

CML results from increase in cells of the granulocytic lineage including neutrophils, eosinophils, and basophils. This mainly caused by a fusion of portion of BCR gene on chromosome 22q with portion of ABL1 gene known as Philadelphia chromosome. [4] || L1: a small cell with a high nucleus; a rectangular cytoplasm ratio, or a clefted cell and small inconspicuous nucleoli L2: larger blast cells with irregular nuclear membranes, one or more prominent nucleoli and a relative abundance of cytoplasm. L3: large lymphoblasts with round to oval prominent nucleoli and basophilic cytoplasm
 * **Lymph node drainage:** || There is no specific lymph node drainage information on leukemia. ||
 * **Metastatic spread:** || Leukemia can spread to the brain, liver and bone. ||
 * **Grading:** || There is no grading system available for leukemia. ||
 * **Staging:** || ** Acute Lymphoblastic Leukemia - ALL ** [1]

M0: Minimal myeloid differentiation M1: Poorly differentiated myeloblasts M2: Myeloblastic with differentiation M3: Promyelocytic M4: Myeloblastic and monoblastic M5: Monoblastic M6: Erythroleukemic M7: Megakaryoblastic
 * Acute Myelogenous Leukemia - AML ** [1]

Stage 0: low risk; blood lymphocytosis, marrow, 40% lymphocytes Stage 1: intermediate risk; lymphocytosis with lymphadenopathy Stage 2: intermediate risk; lymphocytosis with enlarged spleen or liver Stage 3: high risk; lymphocytosis with anemia, lymph nodes, liver and spleen may or may not be enlarged Stage 4: high risk; lymphocytosis with thrombocytopenia, anemia and lymphadenopathy, liver and spleen may be enlarged || Prognosis ALL is divided into 3 prognostic groups Good risks Intermediate risks Poor risks The factors indicative of a good prognosis are: Indicators of a poor prognosis are:
 * Chronic Lymphocytic Leukemia - CLL ** [1]
 * **Radiation side effects:** || Radiation therapy for the treatment of leukemia can cause nausea, vomiting and loss of appetite. Patients often lose their hair and can cause the scalp of the skin in the treated area to become red, dry, tender and itchy. [2] ||
 * **Prognosis:** || Acute Lymphoblastic leukemia (ALL)
 * Ages below 30
 * Complete remission within 4 weeks
 * White blood cell count less than 30,000/µL
 * Do not have adverse reaction to cytogenetics
 * Ages 60 and older
 * Precursor B-cells in the white blood cells
 * White blood cell count greater than 100,000/µL
 * Failure to achieve remission in 4 weeks
 * Adverse cytogenetics (t9;22 and 4;11)

Acute Myelogenous Leukemia (AML)

Prognosis Survival rate for AML varies from 15-85% depending on:
 * Risk stratification
 * Adverse karyotype
 * Over 50 years of age
 * If the disease has evolved slowly
 * Myelodysplastic syndrome
 * Poor performance status
 * Impaired organ function
 * Low serum albumin[2]

Usually without treatment, the survival ranges from a few weeks to a few months after diagnosis. The overall 5-year survival is 21% with treatment. If the patient remains leukemia free for more than 5 years they are considered cured. [2]

Chronic Lymphocytic Leukemia (CLL)

RAI and Binet staging is used to approximate length of survival, “based on the number of lymphocytes in the blood and bone marrow, the size of the liver and spleen, presence of  anemia and platelet count.” [1]

Chronic Myelogenous Leukemia (CML)

CML is not curable. Determining factors that decrease the length of survival are: cells in blood or bone marrow CML patients are diagnosed with a phase of disease. The phase classification provides an approximate length of survival.[2] ||
 * Over the age of 60
 * Spleen size > 10cm below the costal margin
 * Platelet counts > 700,000/ul
 * >7% basophils in blood or bone marrow
 * >3% blasts
 * **Treatments:** || Acute Lymphocytic Leukemia (ALL)[2]

Radiation therapy- • Patient may receive total body radiation with the dose totaling 1200cGy (3 days, 200 cGy two times a day) • A helmet field may be used to encompass the meninges. The helmet dose is 1800 cGy, delivered 200 cGy each day for 9 consecutive days • CNS technique is a combination of a helmet and spine field. This helmet field is treated to a total dose of 2400 cGy (150 cGy a day for 16 days). This is combined with a spine field that receives a total of 1500 cGy (150 cGy a day for 10 days) • Testis field may be used that delivers a dose of 400 cGy in a single fraction and is commonly used with total body irradiation (TBI) treatment.

Chemotherapy (induction, consolidation, prophylaxis of overt CNS disease, and maintenance therapy)- • Induction typically involves the use of prednisone or dexamethasone, vincristine, and L-asparaginase, given immediately after the diagnosis. • Consolidation therapy uses high-dose intravenous methotrexate, etoposide (VP-16), and L-asparaginase after remission has been achieved. • The chemotherapeutic agent shown to be most effective in preventing overt CNS disease in several clinical trials is methotrexate given either systemically or intrathecally. • Maintenance therapy involves the use of intravenous mercaptopurine (6-MP) and systemic methotrexate

Bone marrow transplantation- • Involves harvesting of healthy marrow from a suitable donor. • The marrow is then fused into a patient whose diseased marrow has been destroyed or ablated by chemotherapy or TBI

Acute Myelogenous Leukemia (AML)[2]

Radiation therapy- • Patient may receive total body radiation with the dose totaling 1200cGy (3 days, 200 cGy two times a day)

Chemotherapy (remission induction and postinduction consolidation/maintenance)- • The drugs used in remission induction therapy are cytosine arabinoside combined with an anthracycline antibiotic such as daunorubicin, doxorubicin, or idarubicin. • Cytosine arabinoside (Cytarabine) is used for consolidation/maintenance therapy.

Bone marrow transplantation- • Involves harvesting of healthy marrow from a suitable donor. • The marrow is then fused into a patient whose diseased marrow has been destroyed or ablated by chemotherapy or TBI

Chronic Myelogenous Leukemia (CML)[1]

Radiation therapy- • Patient may receive total body radiation with the dose totaling 1200cGy (3 days, 200 cGy two times a day) • Palliative radiation therapy is used for localized masses of lymphoid tissue and/or enlarged spleen. (AP/PA delivering 100 cGy for 5 days totaling 500 cGy)

Chemotherapy- • The drugs used are alpha-interferon, busulfan, and hydroxyurea. • What had been standard therapy with interferon and ara-C has given way in recent years to therapy with the specific bcr- abl tyrosine kinase inhibitor imatinib.

Bone marrow transplantation- • Involves harvesting of healthy marrow from a suitable donor. • The marrow is then fused into a patient whose diseased marrow has been destroyed or ablated by chemotherapy or TBI • Allogenic bone marrow transplantation is the only curative treatment for CML || [2] Leukemia. Cancer Compass.http://www.cancercompass.com/leukemia-information/causes-and-risk-factors.htm. Accessed July 3, 2012.
 * **TD 5/5:** || [[image:leukima.jpg]] ||
 * **References:** || [1] Hilsendager, E. //Leukemias//. [PowerPoint]. La Crosse, WI: UW-L Medical Dosimetry Program; 2012.

[3] Chao KS, Perez C, Brady L. //Radiation Oncology Management Decisions.// 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.

[4] Hoppe TR, Phillips LT, Roach M. //Leibel and Phillips Textbook of Radiation Oncology//. 3rd Ed. Philadelphia, PA: Saunders, Elsevier; 2010. ||

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