Title: Acute Lymphoblastic Leukemia
1Acute Lymphoblastic Leukemia
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 -
3Introduction
- 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)
4Introduction to pediatric neoplastic disease and
tumor
- Leukemia and a more pronounced rise in central
nervous system tumor - Boy gt girl
5Leukemia
- 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
6Acute 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.
7Acute 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.
8Acute 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.
9Acute 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.
10Clinical manifestations
- Protean
- Bone marrow failure Organ infiltration
- Common symptoms
- Fever ( 60)
- Malaise ( 50)
- Pallor ( 40)
11Etiology
- Unknown ( usually)
- Hereditary
- Downs syndrome
- Leukemia in siblings
- Chemicals
- Chronic benzene exposure
- Alkylating agents
- Ionizing radiation
- Predisposing hematological disease ( MPD, AA)
- Viruses ( HTLV-1)
12Diagnostic criteria
- ALL is often difficult to diagnose.
- The early signs may be similar to the flu or
other common diseases.
13Diagnostic 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
14Diagnostic 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).
15Diagnostic criteria
- Cytochemistry study and surface marker study
confirm the lymphoid origin .
16Diagnostic 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.
17V-25 Leukemic cells in acute lymphoblastic
leukemia characterized by round or convoluted
nuclei, high nuclear/cytoplasmic ratio and
absence of cytoplasmic graulnes.
18Differential diagnosis
- AML.
- MDS.
- Non-Hodgkins lymphoma with bone marrow
involvement or with leukemic change. - CLL.
19Differential diagnosis
- Viral infection with lymphocytosis
- CML with acute blastic crisis.
20(No Transcript)
21Acute lymphoblastic leukemia
22Laboratory examinations
- Full blood count
- Coagulation screening esp AML M3.
- Biochemical screening
- Chest radiography
- Bone marrow aspiration
- Immunophenotyping
- Cytogenetics molecular studies
- Lumbar puncture ( CNS involvement)
23Complications
- Cerebral hemorrhage, pul. hemorrhage or other
vital organ hemorrhage. - Infection(sepsis or septic shock ) , pulmonary
edema. - Tumor lysis syndrome.
24Complications
- Infiltration syndrome(CNS, GI tract or gonads).
- Coagulopathy before or after chemotherapy.
- Anemia.
25Risk Grouping of TPOG (ALL)
- Standard Risk
- High Risk CNS leukemia, cranial nerve palsy,
testicular leukemia, pre-B ALL t(119) or
E2A-PBX1 fusion
26Very 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)
27Poor Prognosis (I)
- Acute lymphoblastic leukemia
28Relapse
- Bone marrow the most common site,
- blast cell increase
- CNS IICP ( vomiting, headache,
- papilledema, lethargy)
- Convulsion
- Behavior disturbance
- Testis painless swelling
29Survival 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).
30Recurrent
- The most important extramedullary sites of
relapse are the CNS and the testes.
31Treatment
- Chemotherapy reach to remission (blastlt5)
- CNS prophylaxis
- Intrathecal C/T
- Cranial irradiation
- Bone marrow transplantation
-
32Management 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.
33Management and treatment
- Chemotherapy(include remission induction,
consolidation maintenance. - CNS prophylaxis with chemotherapeutic
agents(methotrexate 1015mg, intrathecal
injection).
34Management and treatment
- Blood transfusion(component therapy)
- Nutritional support
- Bone marrow transplantation
- Growth factor
35Treatment
- The primary treatment for ALL is chemotherapy.
- Radiation therapy may be used in certain cases
- Bone marrow transplantation is being studied in
clinical trials.
36Treatment 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 .
37Treatment 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)
41Radiation Therapy
- uses x-rays or other high-energy rays to kill
cancer cells and shrink tumors.
42Treatmet 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.
43Bone 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.
44Bone 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.
45Treatment
- Induction 4 weeks
- Hyhration.
- Allopurinol
- Vincristine iv qw Prednisolone po qd
- L- asparaginase
- Mediastinum or spine tumor R/T
46Treatment
- CNS prophylaxis
- Intrathecal ingestion methotrexate
- Intrathecal ingestion methotrexate , Ara-C,
hydrocortisone - High riskIntrathecal ingestion C/TR/T
47THANKS !