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AML/ALL

AML/ALL. By: Brittni McClellan. Classifications. Acute Myelogenous Leukemia Cell Type: Myeloid Blast (>20%). Acute Lymphocytic Leukemia Cell Type: Lymphoblast (>20%). AML vs ALL. ALL: CD10, CD19, CD20, CD22, TDT. AML: CD 11, CD 13, CD33, CD34, CD117 Myeloperoxidase.

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AML/ALL

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  1. AML/ALL By: Brittni McClellan

  2. Classifications • Acute Myelogenous Leukemia • Cell Type: Myeloid Blast (>20%) • Acute Lymphocytic Leukemia • Cell Type: Lymphoblast (>20%)

  3. AML vs ALL ALL: CD10, CD19, CD20, CD22, TDT AML: CD 11, CD 13, CD33, CD34, CD117 Myeloperoxidase

  4. Flow Cytometry Reading Myeloperoxidase + CD34 +

  5. AML - description • Description: • Block in Differentiation/Unregulated Proliferation of Myeloid Progenitor Cells • Ras (Proto-Oncogene) is mutated in 1/3 of patients. • Pathophysiology: • Poor Prognosis: • MLL Gene at 11q23, Monosomy 7 • Favorable Prognosis: • T(8;21), inv(16) • T(15;17) (PML/RARA) – M3 Type • Acute Promyelocytic Leukemia (APL) • Disruption of Retinoic Acid Receptor (RAR) • Associated with DIC • Presence of Auer Rods (Peroxidase-Positive Cytoplasmic Inclusions) Acute Megakaryoblastic Leukemia: Associated with Down’s Syndrome

  6. AML – H&P • Patient History: • Few Symptoms/Vague • Fever • Pallor • Weight Loss/Anorexia • Fatigue • Bleeding • Bone/Joint Pain • Exposure to Benzene/Radiation • Physical Exam: • Signs of Anemia • Pallor, Fatigue, Headache, Dyspnea, Systolic Flow Murmur • Signs of Thrombocytopenia • Petechiae, Bruising, Epistaxis, Gingival Bleeding • Signs of Infection • Fever, Lingering Bacterial Infections • Other • Hepatosplenomegaly, Lymphadenopathy, Gingival Hyperplasia, Papilledema • Colorless or Slightly Purple Subcutaneous Nodules • Blueberry Muffin Lesions of Leukemia Cutis (Neonates)

  7. AML - Diagnosis Diagnosis: • CBC: • ↓ Hemoglobin/Hematocrit (Anemia) • Thrombocytopenia • ↓ WBC Peripheral Smear • ↑ PT/PTT • Electrolytes: • Hyperkalemia • Hypocalcemia • Hyperphosphatemia • Hyperuricemia Diagnostic Procedures: • Southern Blotting • Reverse Transcriptase-PCR • Fluorescence in Situ Hybridization • Bone Marrow Aspirate: • >20% Leukemic Myeloblasts • Immunophenotyping: • Myeloid Blast +: 90% of Cases • CD11b, CD13, CD14, CD 15, CD33, CD36 • Myeloperoxidase • Lymphoid Markers: 30-60% of Cases • Megakaryocytic: • CD41, CD42, CD61

  8. AML – Morphology and cytochemistry Diagnosis: • Morphology: • Large Blasts with Low Nuclear/Cytoplasmic Radio • Multiple Nucleoli and Cytoplasmic Granules • Auer Rods • Cytochemistry: • Myeloperoxidase + • Sudan Black + Sudan Black Stain

  9. AML – treatment • Medication: • 6-9 Months Intensive Chemotherapy in Cycles • Anthracylines • Doxorubicin • Daunomycin • Mitoxantrone • Adjuncts • Etoposide, Gemtuzumab, Dexamethasone, L-Asparaginase, 6-Thioguanine • M3 Variant:High Rate of Remission Induction with all Trans-Retinoic Acid in APL. • 85% of Cases Achieve Remission

  10. Tumor lysis Syndrome • Metabolic Consequences from the release of cellular contents of dying leukemic cells • Consequences: • Hyperuricemia  Renal Failure • Hyperkalemia • Hyperphosphatemia • Hypocalcemia • Treatment: • Hydration with Fluid Containing Bicarbonate • Allopurinol

  11. ALL - description • Description: • Malignant proliferation of WBCs • Characterized by an excess of lymphoblasts • Associations with Risk: • Low Risk: • Trisomy 4 or Trisomy 10 • T(12;21) • WBC < 50,000 at Diagnosis • TdT+ • Standard Risk: • B Phenotype • WBC < 50,000 at Diagnosis • High Risk: • WBC >50,000 at Diagnosis • Age >10 Years • T Phenotype • 9:22 Translocation ALL is the Most Common Cancer of Childhood.

  12. ALL - Pathophysiology • Multiple Genetic Mutations  Rapid Clonal Proliferation • Lack of Cell Maturation • Resistance to Apoptosis • Crowding of Normal Bone Marrow Precursors  Ineffective Hematopoiesis • Associated Conditions: • Trisomy 21 • Li-Fraumeni Syndrome • Neurofibromatosis Type 1 • Ataxia Telangiectasia • Bloom Syndrome • Immunodeficiencies

  13. ALL – H&P • Patient History: • Few Symptoms/Vague • Bone Pain, Limp, Refusal to Bear Weight • Infiltrative Disease of Marrow • Pathological Fractures • Pallor • Weight Loss/Anorexia • Fatigue, Headache • Bleeding//Easy Bruising/Epistaxis • Physical Exam: • Signs of Anemia • Pallor, Fatigue, Headache, Dyspnea, Systolic Flow Murmur • Signs of Thrombocytopenia • Petechiae, Bruising, Epistaxis, Gingival Bleeding • Signs of Infection • Fever, Lingering Bacterial Infections • Other • Hepatosplenomegaly, Lymphadenopathy, Bone Tenderness, Hypopyon (Layering of Leukemia Cells in the Anterior Chamber of the Eye), Painless Testicular Enlargement, Swelling of the Face (Superior Vena Cava Syndrome). • Colorless or Slightly Purple Subcutaneous Nodules • Blueberry Muffin Lesions of Leukemia Cutis (Neonates)

  14. ALL - Diagnosis Diagnosis: • CBC: • ↓ Hemoglobin/Hematocrit (Anemia) • ↑ / ↓ WBC Count • Thrombocytopenia • Electrolytes: • Hyperkalemia • Hypocalcemia • Hyperphosphatemia • Hyperuricemia • Peripheral Smear: • Leukemic Lymphoblasts Diagnostic Procedures: • Imaging: • 5-10% have a Mediastinal Mass • Bone Marrow Aspirate: • >25% Leukemic Lymphoblasts • PAS+ • Immunophenotyping: • Precursor B: • CD10, CD19, CD 20, CD22, TdT, cALLA • Precursor T • CD2, CD3, CD5, CD7, TdT

  15. ALL – treatment • Medication: • Remission Induction • Vincristine • Adjuncts • Prednisone/Dexamethasone, L-Asparaginase, Anthracycline • Maintenance: • Low Risk: • Vincristine + Methotrexate Weekly (Oral) • High Risk: • Cyclophosphamide + Cytarabine + Methotrexate + Vincristine + Asparginase • CNS Prophylaxis: Cytarabine (AraC)

  16. Question 1 • A four-year-old girl is being evaluated for anemia. She originally presented to her pediatrician with her father who stated that she "hadn't seemed herself." She was becoming easily fatigued and uncharacteristically cranky. He also thought she seemed to be bruising from only minor trauma. Her exam reveals cervical and axillary lymphadenopathy. A complete blood count revealed a hemoglobin of 7.1 g/dL, platelets of 50,000, and a white blood cell count of 3,000. Which of the following is most likely to be seen on peripheral blood smear? • Myeloblasts with Auer rods • Large, closely apposed blast cells with minimal cytoplasm intermixed with white spaces filled with debris  • Stacks of red blood cells • Lymphoblasts with cytoplasmic aggregates of PAS positive material • A microcytic anemia with target cells and hypochromic pencil-shaped cells c) Lymphoblasts with cytoplasmic aggregates of PAS positive material

  17. Question 2 • A 55-year-old male with fever, fatigue, generalized weakness, and bleeding gums for the past 3 weeks presents to his family physician. On exam, he has bilateral submandibular lymphadenopathy and hepatosplenomegaly. CBC demonstrates decreased RBCs and mature WBCs. The patient is referred to an oncologist, and a bone marrow aspiration is performed, demonstrating >20% myeloblasts with Auer rods that are myeloperoxidase positive. What is the most likely chromosomal translocation that is responsible for this patient's clinical presentation and lab results? • 15;17 • 29;22 • 314;18 • 411;14 • 58;14 a) 15;17

  18. Question 3 • A 13-year-old male presents to clinic with fatigue and fever. He has been spiking fevers for the past several weeks. He has no significant past medical history and has been growing and developing well. His vital signs are stable with the exception of a temperature of 38.1 C. Physical examination is notable for pallor and hepatosplenomegaly. A complete blood count returns with leukocytosis of 110,000. Subsequently, a bone marrow biopsy reveals 30% lymphoblasts. Which of the following is true regarding his illness? • The 9:22 translocation denotes a better prognosis • Terminal deoxynucleotidyl transferase staining is likely positive on the abnormal cells • The 12:21 translocation denotes a poor prognosis  • This patient's age is a good prognostic factor  • B-cell phenotype decreases the risk of CNS involvement b) Terminal deoxynucleotidyl transferase staining is likely positive on the abnormal cells

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