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Acute leukemia in children 2021
- 1. Pediatric Oncology Classification, Epidemiology, Clinical Features, Prognosis Prof. Imran Iqbal Fellowship in Pediatric Neurology (Australia) Prof of Paediatrics (2003-2018) Prof of Pediatrics Emeritus, CHICH Prof of Pediatrics, CIMS Multan, Pakistan
- 2. It contains estimated 200 Billion Stars, the sun lies roughly 27,000 light-years from the centre of the galaxy. And there are estimated minimum 100 Billion Galaxies in the Universe.
- 3. Pediatric Oncology - Epidemiology • Malignancies are one of the leading causes of death in children under 15 years of age • It is estimated that approximately 7500- 8000 children less than 18 years get cancer, every year in Pakistan.
- 4. Pediatric Oncology – Types of Malignancies Pakistan Data Disease Percentage Leukemia 35 Lymphoma 20 Bone Tumor 08 Soft Tissue Sarcoma 07 Brain Tumor 07 Retinoblastoma 06 Neuroblastoma 04 Wilms Tumor 04 Germ Cell Tumor 03 Others 06
- 7. Pediatric Oncology Acute Leukemia in Children Classification, Epidemiology, Etiology Clinical Features, Diagnosis, Complications, Management, Prognosis Prof. Imran Iqbal Fellowship in Pediatric Neurology (Australia) Prof of Paediatrics (2003-2018) Prof of Pediatrics Emeritus, CHICH Prof of Pediatrics, CIMS Multan, Pakistan
- 8. Acute Leukemia Definition • Acute Leukemia is an uncontrolled neoplastic clonal proliferation of Hematopoietic cells • Unregulated proliferation of Hematopoietic cells occurs as a result of development of Genetic abnormalities in precursor cells • Malignant Hematopoietic cells are found in blood, bone marrow, reticulo-endothelial system and in other tissues
- 9. Acute Leukemia Epidemiology • Acute Leukemia – 30 % of all childhood malignancies • Incidence – 4 patients per 100,000 children per year • Age – below 15 years, commonly below 5 years
- 10. Acute Leukemia – Etiology • Genes – certain genes increase risk of Leukemia • Genetic Diseases – Down syndrome -- Immuno-deficiency diseases • Radiations – before or after birth • Chemicals – benzene, pesticides, unknown • Viral infections – EB virus, others viruses
- 11. Bone Marrow Cells - Development
- 12. Acute Leukemia – Types • Acute Lymphoblastic Leukemia (ALL) – 75 % • Acute Myeloid Leukemia (AML) – 20 %
- 14. Acute Lymphoid Leukemia Clinical Features
- 15. Case scenario • A 5 year old girl presents with pallor, fever, lethargy and frequent pains and aches in the limbs for the last 3 weeks • She has developed blue spots on body for the last 2 days • On examination, she has petechiae on the face and limbs. • Multiple Cervical, Axillary and Inguinal Lymph nodes (5 to 8 nodes in each area) are bilaterally palpable • Lymph nodes are 1 – 2 cm in size and non-tender • Liver is palpable by 2 cm below the costal margin • Spleen is palpable by 4 cm below the costal margin • What is the most likely diagnosis ?
- 16. Acute Lymphoid Leukemia Clinical Features • Anemia – Pallor, Lethargy, Anorexia • Thrombocytopenia – Skin purpura, -- prolonged mucosal bleeds • Neutropenia – Fever, Infections • Leukemic Cell Invasion – Lymphadenopathy -- Hepato-splenomegaly -- Bone and joint pains • Others – CNS symptoms (headache, vomiting) -- Testicular enlargement
- 17. Acute Lymphoid Leukemia Differential Diagnosis • Viral Infections – Infectious Mononucleosis • Leukemoid Reaction – Bacterial Infections, Tuberculosis • Aplastic Anemia – Anemia, Neutropenia, Thrombocytopenia • ITP (Immune Thrombocytopenia) – Thrombocytopenia only • Acute Myeloid Leukemia – Myeloblasts, Myeloid series • Lymphoma – Mature Lymphoid cell proliferation with Lymphadenopathy but no blood or bone marrow invasion
- 19. Acute Lymphoid Leukemia Clinical Diagnosis • Anemia – Pallor, Lethargy, Anorexia • Thrombocytopenia – Skin purpura, -- prolonged mucosal bleeds • Neutropenia – Fever, Infections • Leukemic Cell Invasion – Lymphadenopathy -- Hepato-splenomegaly -- Bone, joint pains • Others – CNS symptoms (headache, vomiting) -- Testicular enlargement
- 20. Acute Lymphoid Leukemia Lab Diagnosis – Initial • Anemia – moderate to severe • Thrombocytopenia – • Leukocytosis – Lymphocytosis, Neutropenia • Peripheral Blood Examination – Immature cells / Lymphoblasts • Bone Marrow Examination – Blast Cells > 25 %
- 21. Acute Lymphoid Leukemia Lab Diagnosis – Advanced • Bone Marrow Examination – Blast Cells > 25 % • Immuno-phenotyping (malignant cell lineage) – -- B – lymphoblastic – 85 % -- T - lymphoblastic – 15 % • Chromosomal abnormalities (Karyotype, PCR, FISH) – Translocations, Diploidy, Trisomy
- 22. Acute Lymphoid Leukemia Lab Diagnosis – Extent of Disease • X-ray Chest – Mediastinal mass (Thymus, lymphadenopathy) • CSF Examination – for CNS leukemia • USG abdomen – Organ disease (Liver, Spleen, Testes, Ovaries) • CT Chest / Abdomen – Lymphadenopathy, tissue infilteration
- 23. Acute Lymphoid Leukemia Lab Diagnosis – Health Status • Basic profile – CBC, LFT, RPM • Infections – Viral markers (HBsAg, HCV), Bacterial cultures • Coagulation profile – PT, APTT • Tumor Lysis Profile – Electrolytes, Uric acid, Calcium, Phosphate • Echocardiography – Myocardium
- 25. Acute Lymphoid Leukemia Risk Classification Standard Risk • Age = 1 – 10 years • Initial TLC count < 50,000 • B – cell • Cytogenetics – Normal / Favourable • Response to therapy - Rapid High Risk • Age < 1 year or > 10 years • Initial TLC count > 50,000 • T – cell • Cytogenetics – Abnormal / Unfavorable • Response to therapy - Slow
- 26. Acute Lymphoid Leukemia Principles of Management • Management of ALL is according to standard protocols in specific centers • Objective of treatment is initially to achieve a remission of disease and later to cure the disease • Management is divided into different phases • Different combinations of cytotoxic medications (chemotherapy) are given • High Risk ALL is given more intensive treatment • Duration of treatment is usually 3 years
- 27. Acute Lymphoid Leukemia Phases of Management • Induction of remission – first 6 weeks • Consolidation phase – next 4 weeks • Interim maintenance phase – 6 months • Delayed Intensification of treatment – 4 weeks • Maintenance phase – 30 months
- 28. Acute Lymphoid Leukemia Induction of Remission • Induction of Remission is during initial 4 – 6 weeks • Objective of Induction of Remission phase is to reduce and eradicate leukemic cells from bone marrow • Medications • Vincristine • Asparaginase • Prednisolone / Dexamethasone • Daunorubicin (high-risk ALL)
- 29. Acute Lymphoid Leukemia Maintenance phase • Maintenance phase lasts 2 – 3 years • Objective of Maintenance phase is to eradicate all leukemic cells from the body • Medications • Methotrexate • Mercaptopurine • Vincristine (monthly) • Corticosteroid (monthly)
- 30. Acute Lymphoid Leukemia Supportive Treatment • Blood component transfusions (Packed RBCs, Platelets) • Neutrophil stimulation factors (GM-CSF for neutropenia) • Antibiotics – for prophylaxis and treatment of infections • Anti-emetics – for chemotherapy induced emesis • Tumor Lysis Syndrome – fluids, allopurinol • Nursing Care – IV sites, mouth, skin • Nutritional support – High calorie, palatable diet • Psychosocial support – Patients and families
- 31. Acute Lymphoid Leukemia Treatment of Relapse • Relapse of ALL is seen in 20 – 30 % of patients • Treatment of Relapse is with more intensive chemotherapy • Bone Marrow Transplant (allogenic sibling donor) • Palliative treatment is given to children when cure is not possible
- 33. Acute Lymphoid Leukemia Factors for Good Prognosis • Good Prognosis • Age 1 - 10 years • Gender – females • Initial WBC (white blood cell) count < 50,000 • B lymphocytes • Cytogenetics favorable • Response to treatment good • Poor Prognosis • Complications of disease – Hyperleukocytosis, CNS disease, Relapse during treatment • Complications of treatment – Infections, Tumor lysis syndrome
- 34. Acute Lymphoid Leukemia Prognosis • Relapse of ALL is seen in 20 – 30 % of patients • Five year survival is 50 – 80 % in good centers • No Relapse in 5 - 10 years after diagnosis of ALL is considered a cure of Acute Lymphoid Leukemia
- 36. Acute Myeloid Leukemia Clinical Features • Anemia – Pallor, Lethargy, Anorexia • Thrombocytopenia – Skin purpura -- prolonged mucosal bleeds • Neutropenia – Fever, Infections • Leukemic Cell Invasion – Hepato-splenomegaly -- Bone pains -- Blueberry muffin skin lesions -- gingival swelling
- 37. Acute Myeloid Leukemia Lab Diagnosis • Anemia – moderate to severe • Thrombocytopenia – • Leukocytosis – premature Myeloid series cells • Peripheral Blood Examination – Myeloblasts, Myelocytes • Bone Marrow Examination – Blast Cells > 20 % • Immuno-phenotyping (malignant cell lineage) – Myeoloblasts • Chromosomal abnormalities (Karyotype, PCR, FISH) – Translocations, Inversions
- 38. Acute Myeloid Leukemia Classification • M0 – undifferentiated leukemia • M1 – Myeloblastic leukemia • M2 – Myeloblastic leukemia with differentiation • M3 – Promyelocytic leukemia • M4 – Myelomonocytic leukemia • M5 – Monocytic leukemia • M6 – Erythroleukemia • M7 – Megakaryoblastic leukemia
- 39. Acute Myeloid Leukemia Principles of Management • Management of AML is difficult and prognosis is poor • Objective of treatment is initially to achieve a remission • Management is started with Induction and Intensification phases of cytotoxic chemotherapy • Bone Marrow Transplant is indicated after remission • Palliative treatment is given to children when cure is not possible
- 40. (God speaking to Prophet Muhammad (PBUH) And (remember) Ayub (Job), when he called his Lord saying “I have been afflicted by distress (disease), and You are the most merciful of all those who have mercy” The Holy Quran; surah Al-Anbiya 21:83 In the name of Our Creator Allah, the most Gracious, the most Merciful