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Acute Lymphoblastic Leukemia

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Bone marrow transplantation. Management and treatment ... Bone Marrow Transplantation. Hematopoietic stem cell transplantation is an option for very high-risk ... – PowerPoint PPT presentation

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Title: Acute Lymphoblastic Leukemia


1
Acute Lymphoblastic Leukemia
  • I2 ? ? ?

2
  • 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

3
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)

4
Introduction to pediatric neoplastic disease and
tumor
  • Leukemia and a more pronounced rise in central
    nervous system tumor
  • Boy gt girl

5
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

6
Acute Lymphoblastic Leukemia
  • Childhood acute lymphoblastic leukemia (also
    called acute lymphocytic leukemia or ALL).
  • is a disease in which too many underdeveloped
    infection-fighting white blood cells, called
    lymphocytes, are found in a child's blood and
    bone marrow.

7
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.

8
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.

9
Acute Lymphoblastic Leukemia
  • the most common symptoms of leukemiafever,
    anemia, bleeding and/or bruising ,persistant
    weakness or tiredness, achiness in the bones or
    joints, recurrent infections , difficulty
    breathing (dyspnea) or swollen lymph nodes.

10
Clinical manifestations
  • Protean
  • Bone marrow failure Organ infiltration
  • Common symptoms
  • Fever ( 60)
  • Malaise ( 50)
  • Pallor ( 40)

11
Etiology
  • Unknown ( usually)
  • Hereditary
  • Downs syndrome
  • Leukemia in siblings
  • Chemicals
  • Chronic benzene exposure
  • Alkylating agents
  • Ionizing radiation
  • Predisposing hematological disease ( MPD, AA)
  • Viruses ( HTLV-1)

12
Diagnostic criteria
  • ALL is often difficult to diagnose.
  • The early signs may be similar to the flu or
    other common diseases.

13
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

14
Diagnostic criteria
  • Peripheral blood anemia,thrombocytopenia,
    variable white cell count with or without blasts.
  • Bone marrow hyper-or hypo-cellularity with
    excess of blasts (blastsgt30 of nucleated cells).

15
Diagnostic criteria
  • Cytochemistry study and surface marker study
    confirm the lymphoid origin .

16
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.

17
V-25 Leukemic cells in acute lymphoblastic
leukemia characterized by round or convoluted
nuclei, high nuclear/cytoplasmic ratio and
absence of cytoplasmic graulnes.
18
Differential diagnosis
  • AML.
  • MDS.
  • Non-Hodgkins lymphoma with bone marrow
    involvement or with leukemic change.
  • CLL.

19
Differential diagnosis
  • Viral infection with lymphocytosis
  • CML with acute blastic crisis.

20
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21
Acute lymphoblastic leukemia
22
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)

23
Complications
  • Cerebral hemorrhage, pul. hemorrhage or other
    vital organ hemorrhage.
  • Infection(sepsis or septic shock ) , pulmonary
    edema.
  • Tumor lysis syndrome.

24
Complications
  • Infiltration syndrome(CNS, GI tract or gonads).
  • Coagulopathy before or after chemotherapy.
  • Anemia.

25
Risk Grouping of TPOG (ALL)
  • Standard Risk
  • High Risk CNS leukemia, cranial nerve palsy,
    testicular leukemia, pre-B ALL t(119) or
    E2A-PBX1 fusion

26
Very High Risk
  • WBC gt 100000/mm3
  • T cell
  • lt 1y/o
  • Lymphoblastic lymphoma with bone marrow
    lymphoblasts gt 25
  • t(922) or BCR-ABL fusion
  • t(411) or MLL-AF4 fusion
  • Other MLL gene rearrangement
  • Hypodiploidy ( chr 44 or less)

27
Poor Prognosis (I)
  • Acute lymphoblastic leukemia

28
Relapse
  • Bone marrow the most common site,
  • blast cell increase
  • CNS IICP ( vomiting, headache,
  • papilledema, lethargy)
  • Convulsion
  • Behavior disturbance
  • Testis painless swelling

29
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).

30
Recurrent
  • The most important extramedullary sites of
    relapse are the CNS and the testes.

31
Treatment
  • Chemotherapy reach to remission (blastlt5)
  • CNS prophylaxis
  • Intrathecal C/T
  • Cranial irradiation
  • Bone marrow transplantation

32
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.

33
Management and treatment
  • Chemotherapy(include remission induction,
    consolidation maintenance.
  • CNS prophylaxis with chemotherapeutic
    agents(methotrexate 1015mg, intrathecal
    injection).

34
Management and treatment
  • Blood transfusion(component therapy)
  • Nutritional support
  • Bone marrow transplantation
  • Growth factor

35
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.

36
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 .

37
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

38
  • 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

39
  • 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.

40
  • 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)

41
Radiation Therapy
  • uses x-rays or other high-energy rays to kill
    cancer cells and shrink tumors.

42
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.

43
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.

44
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.

45
Treatment
  • Induction 4 weeks
  • Hyhration.
  • Allopurinol
  • Vincristine iv qw Prednisolone po qd
  • L- asparaginase
  • Mediastinum or spine tumor R/T

46
Treatment
  • CNS prophylaxis
  • Intrathecal ingestion methotrexate
  • Intrathecal ingestion methotrexate , Ara-C,
    hydrocortisone
  • High riskIntrathecal ingestion C/TR/T

47
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