Clinical Manifestations of ALL Infections Bleeding Anemiapallor Extreme fatigue

Clinical manifestations of all infections bleeding

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Clinical Manifestations of ALL Infections Bleeding Anemia/pallor Extreme fatigue malaise Hepatomegaly/splenomegaly and adenopathy Possible CNS manifestations
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Laboratory Findings of ALL Peripheral blood smear Anemia, thrombocytopenia, neutropenia WBC – high counts (>50,000/mm 3 ) more common vs. AML WBC >100,000/mm 3 requires emergent treatments, associated with LDH and uric acid Bone marrow aspiration >30% blasts Staining – myeloperoxidase negative
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Laboratory Findings of ALL Terminal deoxynucleotidyl transferase (TdT) enzyme testing – present Immunophenotyping and cytogenetics Cell surface antigens CD19 & CD20 = B-cell lineage CD12 & CD17 = T-cell lineage CD10 = common ALL antigen neither B nor T Presence of Philadelphia chromosome confers poor prognosis
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Characteristics of ALL Leukemic cells Tend to be smaller than AML blasts Relatively devoid of granules
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Treatment Stratification Age Children: up to 14 years Adolescent and young adult (AYA): 15 – 39 years Adult: > 40 years Risk factors
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Risk Stratification Adult ALL Standard Risk Age < 35 years WBC on presentation < 30,000 Cytogenetics Hyperdiploidy (>50 chromosomes) Trisomy 4,10,17 ETV6-RUNX1 t(12;21)
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Risk Stratification Adult ALL High Risk Age > 35 years WBC on presentation >30,000 Cytogenetics Philadelphia chromosome + Hypodiploidy (<44 chromosomes) Complex karyotype (>5 abnormalities) t(4;11) MLL rearrangement t(3;14) MYC Know the major age WBC count
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Treatment of ALL Four phases of treatment 1. Induction chemotherapy 2. Post-remission consolidation chemotherapy 3. CNS prophylaxis (chemotherapy/radiation) 4. Maintenance therapy
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Treatment of Adult ALL Age <65 vs. > 65 years old Co-morbidities Presence of Philadelphia chromosome (Ph + )
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Treatment of Ph + Adult ALL Induction Therapy < 65 yrs old Clinical Trial Chemo + TKI Corticosteroids + TKI >/= 65 yrs old Clinical Trial Chemo + TKI Corticosteroids + TKI TKI = tyrosine kinase inhibitor (imatinib, dasatinib, nilotinib, ponatinib, ) NCCN Guidelines Acute Lymphoblastic Leukemia version 1.2018
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Treatment of Ph - adult ALL Induction Therapy < 65 yrs old Clinical Trial Multi-agent chemotherapy >/= 65 yrs old Clinical Trial Multi-agent chemotherapy Palliative corticosteroids NCCN guidelines Acute Lymphoblastic Leukemia version 1.2018
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Multi-Agent Chemotherapy Induction chemotherapy Anthracycline (doxorubicin/daunorubicin) Vincristine Steroid (prednisone or dexamethasone) Asparaginase (pegaspargase) Cyclophosphamide High dose methotrexate, cytarabine Mercaptopurine
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Treatment of ALL Consolidation Allogeneic transplant if donor available Continue multi-agent chemotherapy Plus TKI for Ph + Corticosteroids Plus TKI for Ph +
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Treatment of ALL CNS prophylaxis Intravenous high dose methotrexate, high dose cytarabine
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  • Spring '17
  • Leukemia, Acute myeloid leukemia

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