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Acute Lymphoblastic Leukemia. I2 黃 柏 瑋. Malignancy remains the major cause of death to disease between the age of 1 and 15 years The precise cause of childhood cancer is unknow Leukemia , Neuroblastoma , Wilms tumor , retinoblastoma and tumor of liver. Introduction.

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Acute Lymphoblastic Leukemia

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Acute Lymphoblastic Leukemia

I2 黃 柏 瑋

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  • Malignancy remains the major cause of death to disease between the age of 1 and 15 years

  • The precise cause of childhood cancer is unknow

  • Leukemia, Neuroblastoma, Wilms tumor , retinoblastoma and tumor of liver

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  • Leukemia– the most common malignancy in childhood.

  • Acute leukemia– 97%

    Acute lymphoblastic leukemia– 75%

    Acute myeloblastic leukemia– 20%

  • Chronic leukemia– 3%

    Chronic myelogenous leukemia (Ph positive)

    Juvenile myelomonocytic leukemia ( JMML)

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Introduction to pediatric neoplastic disease and tumor

  • Leukemia and a more pronounced rise in central nervous system tumor

  • Boy > girl

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  • The most common childhood cancer ( 1/3 of pediatric malignancies ).

  • Acute lymphoblastic leukemia (ALL) represents about 75 % (peak incidence at age 4 years).

  • Acute myeloid leukemia (AML) accounts for about 20 % of leukemia (stable from birth through age 10)

  • Others : CML

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Acute Lymphoblastic Leukemia

  • Childhood acute lymphoblastic leukemia (also called acute lymphocyticleukemia or ALL).

  • is a disease in which toomanyunderdeveloped infection-fighting white blood cells, called lymphocytes, are found in a child's blood and bonemarrow.

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Acute Lymphoblastic Leukemia

  • These abnormal cells reproduce very quickly and do not function as healthy white blood cells to help fight infection.

  • the most common form of leukemia

  • the most common kind of childhood cancer.

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Acute Lymphoblastic Leukemia

  • In the United States, about 3,000 children each year are found to have ALL

  • Peak incidence occurs from 3 to 5 years of age.

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Acute Lymphoblastic Leukemia

  • the most common symptoms of leukemia:fever, anemia, bleeding and/or bruising ,persistant weakness or tiredness, achiness in the bones or joints, recurrent infections , difficulty breathing (dyspnea) or swollen lymph nodes.

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Clinical manifestations

  • Protean

  • Bone marrow failure & Organ infiltration

  • Common symptoms

    Fever ( 60%)

    Malaise ( 50%)

    Pallor ( 40%)

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  • Unknown( usually)

  • Hereditary

    Down’s syndrome

    Leukemia in siblings

  • Chemicals

    Chronic benzene exposure

    Alkylating agents

  • Ionizing radiation

  • Predisposing hematological disease ( MPD, AA)

  • Viruses ( HTLV-1)

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Diagnostic criteria

  • ALL is often difficult to diagnose.

  • The early signs may be similar to the flu or other common diseases.

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Diagnostic criteria

  • bone marrow aspiration and biopsy

  • complete blood count (CBC)

  • additional blood tests

  • computerized tomography scan

  • magnetic resonanec imaging (MRI)

  • x-ray

  • ultrasound

  • lymph node biopsy

  • spinal tap/lumbar puncture

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Diagnostic criteria

  • Peripheralblood: anemia,thrombocytopenia, variable white cell count with or without blasts.

  • Bonemarrow: hyper-or hypo-cellularity with excess of blasts (blasts>30% of nucleated cells).

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Diagnostic criteria

  • Cytochemistry study and surface marker study confirm the lymphoid origin .

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Diagnostic criteria

  • blood tests to count the number of each of the different kinds of blood cells..

  • If the results of the blood tests are not normal, a doctor may do a bone marrow biopsy .

  • The chance of recovery (prognosis) depends on how the leukemia cells look under a microscope.

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V-25Leukemic cells in acutelymphoblasticleukemia characterized by round or convoluted nuclei, high nuclear/cytoplasmic ratio and absence of cytoplasmic graulnes.

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Differential diagnosis

  • AML.

  • MDS.

  • Non-Hodgkin‘s lymphoma with bone marrow involvement or with leukemic change.

  • CLL.

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Differential diagnosis

  • Viral infection with lymphocytosis

  • CML with acute blastic crisis.

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Acute lymphoblastic leukemia

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Laboratory examinations

  • Full blood count

  • Coagulation screening – esp AML M3.

  • Biochemical screening

  • Chest radiography

  • Bone marrow aspiration

  • Immunophenotyping

  • Cytogenetics & molecular studies

  • Lumbar puncture ( CNS involvement)

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  • Cerebral hemorrhage, pul. hemorrhage or other vital organ hemorrhage.

  • Infection(sepsis or septic shock ) , pulmonary edema.

  • Tumor lysis syndrome.

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  • Infiltration syndrome(CNS, GI tract or gonads).

  • Coagulopathy before or after chemotherapy.

  • Anemia.

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Risk Grouping of TPOG (ALL)

  • Standard Risk

  • High Risk– CNS leukemia, cranial nerve palsy, testicular leukemia, pre-B ALL t(1;19) or E2A-PBX1 fusion

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Very High Risk

  • WBC > 100000/mm3

  • T – cell

  • < 1y/o

  • Lymphoblastic lymphoma with bone marrow lymphoblasts > 25%

  • t(9;22) or BCR-ABL fusion

  • t(4;11) or MLL-AF4 fusion

  • Other MLL gene rearrangement

  • Hypodiploidy ( chr 44 or less)

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Poor Prognosis (I)

  • Acute lymphoblastic leukemia

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  • Bone marrow– the most common site,

    blast cell increase

  • CNS– IICP ( vomiting, headache,

    papilledema, lethargy)


    Behavior disturbance

  • Testis– painless swelling

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Survival rates

  • 75 % to 80% of children with ALL survive at least 5 years from diagnosis with current treatments that incorporate systemic therapy (e.g., combination chemotherapy) and specific central nervous system (CNS) preventive therapy (i.e., intrathecal chemotherapy with or without cranial irradiation).

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  • The most important extramedullary sites of relapse are the CNS and the testes.

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  • Chemotherapy– reach to remission(blast<5%)

  • CNS prophylaxis

    Intrathecal C/T

    Cranial irradiation

  • Bone marrow transplantation

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Management and treatment

  • Hydration, prevention of hyperuricemia and tumor lysis syndrome.

  • Antibiotics, may need the 3rd generation of cephalosporin or other strong antibiotics, even antifungal agents.

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Management and treatment

  • Chemotherapy(include remission induction, consolidation & maintenance.

  • CNS prophylaxis with chemotherapeutic agents(methotrexate 10~15mg, intrathecal injection).

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Management and treatment

  • Blood transfusion(component therapy)

  • Nutritional support

  • Bone marrow transplantation

  • Growth factor

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  • The primary treatment for ALL is chemotherapy.

  • Radiation therapy may be used in certain cases

  • Bone marrow transplantation is being studied in clinical trials.

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Treatment : Chemotherapy

  • uses drugs to kill cancer cells

  • drugs may be taken by mouth, or may be put into the body by a needle in a vein or muscle.

  • All chemotherapy is stopped after two to three years of treatment .

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Treatment : Chemotherapy


  • Used in induction and reinduction therapy and also given as intermittent pulses during continuation therapy.

  • toxicity :

    fluid retention, increased appetite, transient diabetes, acne, striae, personality changes, peptic ulcer, immunosuppression, osteoporosis, growth retardation; caution in diabetes, fungal infections, and osteonecrosis

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  • toxicity :

    Peripheral neuropathy manifested by constipation, ileus, ptosis, vocal cord paralysis, jaw pain, abdominal pain, loss of deep tendon reflexes; reduce dosage with severe peripheral neuropathy; bone marrow depression; local ulceration with extravasation, SIADH

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  • local rash, hives, anaphylaxis; bone marrow depression, hyperglycemia, hepatotoxicity, and bleeding may occur.


  • Myelosuppression and thrombocytopenia; may cause cardiac arrhythmias immediately following administration and cardiomyopathy after long-term use; nausea, vomiting, stomatitis, and alopecia; extravasation may occur, resulting in severe tissue necrosis; caution with impaired hepatic, renal, or biliary function.

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Methotrexate (Folex PFS)

  • Hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

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Radiation Therapy

  • uses x-rays or other high-energy rays to kill cancer cells and shrink tumors.

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Treatmet for VHR

Induction:(10 weeks)

  • Prednisolone,Vincristine,Idarubicin,



    Consolidation:(8 weeks)

  • 6-MP,MTX,TIT

    Reinduction:(7 weeks)

  • Dexamethasone, ,Vincristine,Idarubicin,



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Bone Marrow Transplantation

  • Hematopoietic stem cell transplantation is an option for very high-risk cases (e.g., Philadelphia chromosome-positive ALL) or those who develop an early relapse in the bone marrow.

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Bone Marrow Transplantation

  • a newer type of treatment.

  • high doses of chemotherapy with or without radiation therapy are given to destroy all of the bone marrow in the body.

  • Healthy marrow is then taken from another person (a donor).

  • autologous bone marrow transplant, is being studied in clinical trials.

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Induction : 4 weeks

  • Hyhration.

  • Allopurinol

  • Vincristine iv qw & Prednisolone po qd

  • L- asparaginase

  • Mediastinum or spine tumor : R/T

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CNS prophylaxis

  • Intrathecal ingestion : methotrexate

  • Intrathecal ingestion : methotrexate ,Ara-C, hydrocortisone

  • High risk:Intrathecal ingestion C/T&R/T

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