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Acute Acute Lymphoblastic Lymphoblastic
LeukemiaLeukemia
I2 黃 柏 瑋
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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
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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)
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Introduction to pediatric neoplastic disease and tumor
Leukemia and a more pronounced rise in central nervous system tumor
Boy > girl
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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
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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.
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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.
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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.
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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.
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Clinical manifestations
Protean Bone marrow failure & Organ infiltration Common symptoms
Fever ( 60%)
Malaise ( 50%)
Pallor ( 40%)
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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)
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Diagnostic criteria
ALL is often difficult to diagnose. The early signs may be similar to the
flu or other common diseases.
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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
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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).
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Diagnostic criteria
Cytochemistry study and surface marker study confirm the lymphoid origin .
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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.
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V-25 Leukemic cells in acute lymphoblastic leukemia characterized by round or convoluted nuclei, high nuclear/cytoplasmic ratio and absence of cytoplasmic graulnes.
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Differential diagnosis
AML. MDS. Non-Hodgkin‘s lymphoma with bone
marrow involvement or with leukemic change.
CLL.
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Differential diagnosis
Viral infection with lymphocytosis CML with acute blastic crisis.
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Acute lymphoblastic leukemia
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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)
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Complications
Cerebral hemorrhage, pul. hemorrhage or other vital organ hemorrhage.
Infection(sepsis or septic shock ) , pulmonary edema.
Tumor lysis syndrome.
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Complications
Infiltration syndrome(CNS, GI tract or gonads).
Coagulopathy before or after chemotherapy.
Anemia.
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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
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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)
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Poor Prognosis (I)
Acute lymphoblastic leukemia
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Relapse
Bone marrow– the most common site,
blast cell increase CNS– IICP ( vomiting, headache,
papilledema, lethargy)
Convulsion
Behavior disturbance Testis– painless swelling
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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).
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Recurrent
The most important extramedullary sites of relapse are the CNS and the testes.
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Treatment Chemotherapy – reach to remission (blast<5%) CNS prophylaxis Intrathecal C/T
Cranial irradiation Bone marrow transplantation
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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.
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Management and treatment
Chemotherapy(include remission induction, consolidation & maintenance.
CNS prophylaxis with chemotherapeutic agents(methotrexate 10 ~ 15mg, intrathecal injection).
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Management and treatment
Blood transfusion(component therapy) Nutritional support Bone marrow transplantation Growth factor
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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.
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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 .
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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
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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
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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.
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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)
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Radiation Therapy
uses x-rays or other high-energy rays to kill cancer cells and shrink tumors.
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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.
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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.
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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.
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Treatment
Induction : 4 weeks Hyhration. Allopurinol Vincristine iv qw & Prednisolone po qd L- asparaginase Mediastinum or spine tumor : R/T
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Treatment
CNS prophylaxis Intrathecal ingestion : methotrexate Intrathecal ingestion : methotrexate ,
Ara-C, hydrocortisone High risk:Intrathecal ingestion C/T&R/T
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THANKS !