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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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slide2
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
Introduction
  • 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
leukemia
Leukemia
  • 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%)

etiology
Etiology
  • 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.
slide17

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)
complications
Complications
  • Cerebral hemorrhage, pul. hemorrhage or other vital organ hemorrhage.
  • Infection(sepsis or septic shock ) , pulmonary edema.
  • Tumor lysis syndrome.
complications24
Complications
  • 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
relapse
Relapse
  • Bone marrow– the most common site,

blast cell increase

  • CNS– IICP ( vomiting, headache,

papilledema, lethargy)

Convulsion

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).
recurrent
Recurrent
  • The most important extramedullary sites of relapse are the CNS and the testes.
treatment
Treatment
  • 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
treatment35
Treatment
  • 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

Prednisone:

  • 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

slide38
Vincristine:
  • 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

slide39
Asparaginase
  • local rash, hives, anaphylaxis; bone marrow depression, hyperglycemia, hepatotoxicity, and bleeding may occur.

Daunorubicin

  • 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.
slide40
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,

Asparaginase,cyclophosphamine,cytarabine,

6-MP,TIT.

Consolidation:(8 weeks)

  • 6-MP,MTX,TIT

Reinduction:(7 weeks)

  • Dexamethasone, ,Vincristine,Idarubicin,

Asparaginase,cyclophosphamine,cytarabine,

6-MP,TIT.

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.
treatment45
Treatment

Induction : 4 weeks

  • Hyhration.
  • Allopurinol
  • Vincristine iv qw & Prednisolone po qd
  • L- asparaginase
  • Mediastinum or spine tumor : R/T
treatment46
Treatment

CNS prophylaxis

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