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
 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
 Leukemia and a more pronounced rise
in central nervous system tumor
 Boy > girl
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 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.
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 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 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
 Protean
 Bone marrow failure & Organ infiltration
 Common symptoms
Fever ( 60%)
Malaise ( 50%)
Pallor ( 40%)
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
 ALL is often difficult to diagnose.
 The early signs may be similar to the
flu or other common diseases.
Diagnostic criteria
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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 criteria
 Peripheral blood:
anemia,thrombocytopenia, variable white
cell count with or without blasts.
 Bone marrow: hyper-or hypo-cellularity
with excess of blasts (blasts>30% of
nucleated cells).
Diagnostic criteria
 Cytochemistry study and surface
marker study confirm the lymphoid
origin .
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-25 Leukemic cells in acute lymphoblastic leukemia
characterized by round or convoluted nuclei, high
nuclear/cytoplasmic ratio and absence of cytoplasmic graulnes.
Differential diagnosis
 AML.
 MDS.
 Non-Hodgkin‘s lymphoma with bone
marrow involvement or with leukemic
change.
 CLL.
Differential diagnosis
 Viral infection with lymphocytosis
 CML with acute blastic crisis.
Acute lymphoblastic leukemia
Laboratory examinations
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Full blood count
Coagulation screening – esp AML M3.
Biochemical screening
Chest radiography
Bone marrow aspiration
Immunophenotyping
Cytogenetics & molecular studies
Lumbar puncture ( CNS involvement)
Complications
 Cerebral hemorrhage, pul. hemorrhage
or other vital organ hemorrhage.
 Infection(sepsis or septic shock ) ,
pulmonary edema.
 Tumor lysis syndrome.
Complications
 Infiltration syndrome(CNS, GI tract or
gonads).
 Coagulopathy before or after
chemotherapy.
 Anemia.
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
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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)
 Acute lymphoblastic leukemia
Relapse
 Bone marrow– the most common site,
blast cell increase
 CNS– IICP ( vomiting, headache,
papilledema, lethargy)
Convulsion
Behavior disturbance
 Testis– painless swelling
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
 The most important extramedullary sites of
relapse are the CNS and the testes.
Treatment
 Chemotherapy – reach to remission (blast<5%)
 CNS prophylaxis
Intrathecal C/T
Cranial irradiation
 Bone marrow transplantation
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 treatment
 Chemotherapy(include remission
induction, consolidation & maintenance.
 CNS prophylaxis with chemotherapeutic
agents(methotrexate 10～15mg,
intrathecal injection).
Management and treatment
 Blood transfusion(component therapy)
 Nutritional support
 Bone marrow transplantation
 Growth factor
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
 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 : 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
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
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.
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
 uses x-rays or other high-energy rays
to kill cancer cells and shrink tumors.
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
 Hematopoietic stem cell transplantation
is an option for very high-risk cases
(e.g., Philadelphia chromosomepositive ALL) or those who develop an
early relapse in the bone marrow.
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.
Treatment
Induction : 4 weeks
 Hyhration.
 Allopurinol
 Vincristine iv qw & Prednisolone po qd
 L- asparaginase
 Mediastinum or spine tumor : R/T
Treatment
CNS prophylaxis
 Intrathecal ingestion : methotrexate
 Intrathecal ingestion : methotrexate ,
Ara-C, hydrocortisone
 High risk:Intrathecal ingestion C/T&R/T
THANKS !