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LEUKEMIA IN CHILDREN

LEUKEMIA IN CHILDREN. Epidemiology. Approximately 2,800 children are diagnosed with ALL in the United States annually. It has a striking peak incidence between 2–6 yr of age and occurs slightly more frequently in boys than in girls. Introduction.

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LEUKEMIA IN CHILDREN

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  1. LEUKEMIA IN CHILDREN

  2. Epidemiology. Approximately 2,800 children are diagnosed with ALL in the United States annually. It has a striking peak incidence between 2–6 yr of age and occurs slightly more frequently in boys than in girls.

  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. 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

  5. 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.

  6. Acute Lymphoblastic Leukemia • the most common symptoms of leukemia:fever, anemia, bleeding and/or bruising, reccurent infections ,persistant weakness or tiredness, • achiness in the bones or joints, difficulty breathing (dyspnea) , adenohepatosplenomegaly

  7. Clinical manifestations • Bone marrow failure & Organ infiltration • Common symptoms Fever ( 60%) Malaise ( 50%) Pallor ( 40%)

  8. 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)

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

  10. Diagnostic criteria • bone marrow aspiration and biopsy • complete blood count (CBC) • additional blood tests, genetic, molecular tests • computerized tomography scan • magnetic resonance imaging (MRI) • x-ray • ultrasound • lymph node biopsy • spinal tap/lumbar puncture

  11. 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).

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

  13. V-25Leukemic cells in acutelymphoblasticleukemia characterized by round or convoluted nuclei, high nuclear/cytoplasmic ratio and absence of cytoplasmic graulnes.

  14. Differential diagnosis • AML. • MDS. • Non-Hodgkin‘s lymphoma with bone marrow involvement or with leukemic change. • Aplastic anemia • HIV infections • EBV • CMV • Systemic form of juvenile chronic arthritis

  15. Acute lymphoblastic leukemia

  16. Laboratory examinations • Full blood count • Coagulation screening – especially AML M3. • Biochemical screening • Chest radiography • Bone marrow aspiration • Immunophenotyping • Cytogenetics & molecular studies • Lumbar puncture ( CNS involvement)

  17. Complications • Cerebral hemorrhage, pulmonary hemorrhage or other vital organ hemorrhage. • Infection(sepsis or septic shock ) , pulmonary edema. • Tumor lysis syndrome. • Hyper K • HyperPo4). • Coagulopathy before or after chemotherapy. • Anemia.

  18. 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

  19. 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)

  20. Poor Prognosis (I) • Acute lymphoblastic leukemia

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

  22. 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).

  23. Treatment • Chemotherapy– reach to remission(blast<5%) • CNS prophylaxis Intrathecal C/T Cranial irradiation • Bone marrow transplantation

  24. 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.

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

  26. 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.

  27. 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

  28. 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

  29. 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.

  30. 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)

  31. Treatment 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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