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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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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
  • 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)

introduction to pediatric neoplastic disease and tumor
Introduction to pediatric neoplastic disease and tumor
  • Leukemia and a more pronounced rise in central nervous system tumor
  • Boy > girl
  • 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
acute lymphoblastic leukemia6
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.
acute lymphoblastic leukemia7
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.
acute lymphoblastic leukemia8
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.
acute lymphoblastic leukemia9
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.
clinical manifestations
Clinical manifestations
  • Protean
  • Bone marrow failure & Organ infiltration
  • Common symptoms

Fever ( 60%)

Malaise ( 50%)

Pallor ( 40%)

  • 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)
diagnostic criteria
Diagnostic criteria
  • ALL is often difficult to diagnose.
  • The early signs may be similar to the flu or other common diseases.
diagnostic criteria13
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
diagnostic criteria14
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).
diagnostic criteria15
Diagnostic criteria
  • Cytochemistry study and surface marker study confirm the lymphoid origin .
diagnostic criteria16
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.

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

differential diagnosis
Differential diagnosis
  • AML.
  • MDS.
  • Non-Hodgkin‘s lymphoma with bone marrow involvement or with leukemic change.
  • CLL.
differential diagnosis19
Differential diagnosis
  • Viral infection with lymphocytosis
  • CML with acute blastic crisis.
laboratory examinations
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)
  • Cerebral hemorrhage, pul. hemorrhage or other vital organ hemorrhage.
  • Infection(sepsis or septic shock ) , pulmonary edema.
  • Tumor lysis syndrome.
  • Infiltration syndrome(CNS, GI tract or gonads).
  • Coagulopathy before or after chemotherapy.
  • Anemia.
risk grouping of tpog all
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
very high risk
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)
poor prognosis i
Poor Prognosis (I)
  • Acute lymphoblastic leukemia
  • Bone marrow– the most common site,

blast cell increase

  • CNS– IICP ( vomiting, headache,

papilledema, lethargy)


Behavior disturbance

  • Testis– painless swelling
survival rates
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).
  • The most important extramedullary sites of relapse are the CNS and the testes.
  • Chemotherapy– reach to remission(blast<5%)
  • CNS prophylaxis

Intrathecal C/T

Cranial irradiation

  • Bone marrow transplantation
management and treatment
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.
management and treatment33
Management and treatment
  • Chemotherapy(include remission induction, consolidation & maintenance.
  • CNS prophylaxis with chemotherapeutic agents(methotrexate 10~15mg, intrathecal injection).
management and treatment34
Management and treatment
  • Blood transfusion(component therapy)
  • Nutritional support
  • Bone marrow transplantation
  • Growth factor
  • The primary treatment for ALL is chemotherapy.
  • Radiation therapy may be used in certain cases
  • Bone marrow transplantation is being studied in clinical trials.
treatment chemotherapy
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 .
treatment chemotherapy37
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

  • 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

  • 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.
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)
radiation therapy
Radiation Therapy
  • uses x-rays or other high-energy rays to kill cancer cells and shrink tumors.
treatmet for vhr
Treatmet for VHR

Induction:(10 weeks)

  • Prednisolone,Vincristine,Idarubicin,



Consolidation:(8 weeks)

  • 6-MP,MTX,TIT

Reinduction:(7 weeks)

  • Dexamethasone, ,Vincristine,Idarubicin,



bone marrow transplantation
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.
bone marrow transplantation44
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.

Induction : 4 weeks

  • Hyhration.
  • Allopurinol
  • Vincristine iv qw & Prednisolone po qd
  • L- asparaginase
  • Mediastinum or spine tumor : R/T

CNS prophylaxis

  • Intrathecal ingestion : methotrexate
  • Intrathecal ingestion : methotrexate ,Ara-C, hydrocortisone
  • High risk:Intrathecal ingestion C/T&R/T