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- 1. 1 Approach to Anemia ALL اطفال سرویس13/06/1399 By: Dr. Merwais Azizyar Supervisor: Assistant clinical professor Dr. Zabehullah Fazli Acute Lymphoblastic Leukemia (ALL)
- 2. 2 Approach to Anemia ALL اطفال سرویس13/06/1399 Outline Of Presentation Introduction Etiology Pathogenesis Clinical presentation Classification Investigation Differential Diagnosis Management
- 3. 3 Approach to Anemia ALL اطفال سرویس13/06/1399 Introduction Leukemia Cancer Blood or Bone marrow Characterized: An abnormal increase of WBC Divided into 2 broad categories depending upon cell lineage – AML , ALL
- 5. 5 Approach to Anemia ALL اطفال سرویس13/06/1399 Introduction … ALL is a malignant disorder of lymphoid progenitor cells both T and B lymphoblasts. Involving a) Bone Marrow b) Other tissue like - Lymph nodes - Thymus - With or without peripheral blood.
- 6. 6 Approach to Anemia ALL اطفال سرویس13/06/1399 Introduction … ALL is a neoplasm composed of immature B (pre- B) or T (pre-T) cells. The most common malignancy accounts 23% Peak age is 2 – 5 years 85% patients are diagnosed b/w ages 2 – 10 years. Worldwide incidence 1:25,000/year USA 3000/year
- 7. 7 Approach to Anemia ALL اطفال سرویس13/06/1399 Etiology Unknown, although several genetic and environmental predisposing factors are associated with childhood leukemia. Genetic - Down syndrome, Turner syndrome, Klinfelter - Fanconi and Diamond black fan anemia - Ataxia telengictasia, Li-Fraumeni syndrome - Blooms syndrome
- 8. 8 Approach to Anemia ALL اطفال سرویس13/06/1399 Etiology … Environmental - Ionizing radiation - Drugs: - Alkylating agents - Poly Benzamide carriers - Mitomycins - Amino analogues - Benzene exposure - Advanced maternal age - Paternal smoking
- 9. 9 Approach to Anemia ALL اطفال سرویس13/06/1399 Pathogenesis T.F loss of function mutation RAS Mutation Tyrosine kinase mutation Genetic Changes Numerical Hyper ploidy (>50) Good Hypo ploidy (< 44) Poor Structural Translocation (9:22) Ph.Chr T.F T.F T.F 6 to 8 changes
- 10. 10 Approach to Anemia ALL اطفال سرویس13/06/1399 Clinical Presentation
- 11. 11 Approach to Anemia ALL اطفال سرویس13/06/1399 Clinical Presentation …
- 12. 12 Approach to Anemia ALL اطفال سرویس13/06/1399 Classification FAB classification Based primarily on the microscopic appearance of the leukemic cells. Prior to 2008, ALL was classified morphologically. - Size - Cytoplasm - Nucleoli - Basophilia
- 14. 14 Approach to Anemia ALL اطفال سرویس13/06/1399 Classification … WHO classification In 2008, the WHO classification of ALL was developed. It is more clinically relevant and could produce meaningful prognostic and treatment decisions.
- 15. 15 Approach to Anemia ALL اطفال سرویس13/06/1399 Classification … WHO classification
- 16. 16 Approach to Anemia ALL اطفال سرویس13/06/1399 Investigation CBC: With differential is the most useful initial test. CBC shows - ANEMIA (Hb<11g/dl) - Thrombocytopenia (<150,000/µl) - Leukopenia (<4000/µl), Normal L. count 50% - Leukocytosis (> 10,000 – 50,000 /µl) 30% ( over 50,000 – 300,000/µl) 20%
- 17. 17 Approach to Anemia ALL اطفال سرویس13/06/1399 Investigation … Peripheral Blood Smear: RBCs Tear drops 1 % normal CBC and PBS. (Bone pain present)
- 18. 18 Approach to Anemia ALL اطفال سرویس13/06/1399 Investigation … Bone marrow examination: The diagnosis of ALL is made by Bone marrow exam which shows: leukemic blasts Lumbar Puncture
- 19. 19 Approach to Anemia ALL اطفال سرویس13/06/1399 Investigation … X-Ray Anterior Mediastinal Mass Tracheal compression lymphadenopathy Thymus infiltration Pre T-Cell ALL Long Bones Demineralization, periosteal elevation, growth arrest lines.
- 20. 20 Approach to Anemia ALL اطفال سرویس13/06/1399 Differential Diagnosis History and physical exam. Non- Malignant Conditions EBV and Cytomegalovirus Lymphadenopathy, Fever, hepatosplenomegaly, anemia ITP Petechia, purpura Hemolytic anemia, aplastic anemia Pallor JRA Fever, joint pain Pertussis High WBC, lymphocytosis, lymphocytes are mature
- 21. 21 Approach to Anemia ALL اطفال سرویس13/06/1399 Differential Diagnosis … Malignant Conditions Hodgkin and non Hodgkin lymphoma Neuroblastoma Retinoblastoma Rhabdomyosarcoma AML
- 22. 22 Approach to Anemia ALL اطفال سرویس13/06/1399 Management ( 24 – 30 months) Therapy for ALL is divided into 4 stages Induction therapy or Specific therapy Intensification or consolidation therapy CNS preventative therapy Maintenance or Continuous therapy
- 23. 23 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… Specific therapy or Induction therapy <5% blasts The first month of therapy Remission: 95 – 98% 4 – 6 weeks 1. Prednisolone 40mg/m2 p.o days 1 – 28 2. Vincristine 1.4mg /m2 i.v days 1, 8,15,22 and 29 3. Daunorubicin 30mg /m2 i.v days 1, 15,29 4. L- Asparaginase 6000 U /m2 i.m days 2 – 20 5. Methotrexate 12 mg IT days 1,8,15, 22
- 24. 24 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… Intensification therapy or Consolidation therapy 2nd phase of treatment IT chemotherapy+sys therapy+ Cranial radiation Drugs: 1. Cyclophosphamide 750mg /m2 i.v days 1 & 15 2. Vincristine 1.4 mg /m2 i.v days 1 & 15 3. Cytosine arabinoside 70mg /m2 s.c/12hr for 6 doses 1-3 & and 15-17
- 25. 25 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… CNS Preventive Therapy Most children with leukemia have subclinical CNS involvement at diagnosis. Starts at beginning of induction therapy Intensifies during consolidation Continues throughout the maintenance phase Methotrexate (1-2yr 8mg, 3yr 10mg, >3yr 12mg ) + lower dose of cranial radiation
- 26. 26 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… Maintenance therapy (6 cycles) Duration: Girls 2.2 yrs., Boys 3.2 yrs. Drugs: 6-Mercaptopurine 75mg /m2 /p.o/daily 12 weeks Methotrexate 15mg /m2/p.o/weekly 12 weeks Vincristine 1.4mg /m2 /i.v pulses/monthly Prednisolone 40mg /m2 p.o/daily days 1 – 7 Daunorubicin and L-Asparaginase
- 27. 27 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… Bone marrow transplantation Rarely used as initial therapy Certain chromosomal abnormalities or very slow response to therapy Early HSCT from a match sibling donor or unrelated match donor. HSCT cure about 50% Tyrosine kinase inhibitors Researches continues…
- 28. 28 Approach to Anemia ALL اطفال سرویس13/06/1399 Management… Long term effects of treatment Obesity Reproductive difficulties Delayed growth Learning difficulties
- 30. 30 Approach to Anemia ALL اطفال سرویس13/06/1399 Reference Nelson Textbook Pediatrics Current 2020 Hemato-Oncology OP GHAI Essential Pediatrics www.cancer.Net