Clinical Manifestations of ALL Infections Bleeding Anemiapallor Extreme fatigue

Clinical Manifestations of ALL • Infections • Bleeding • Anemia/pallor • Extreme fatigue malaise • Hepatomegaly/splenomegaly and adenopathy • Possible CNS manifestations

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

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

Characteristics of ALL • Leukemic cells – Tend to be smaller than AML blasts – Relatively devoid of granules

Treatment Stratification • Age – Children: up to 14 years – Adolescent and young adult (AYA): 15 – 39 years – Adult: > 40 years • Risk factors

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)

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

Treatment of ALL • Four phases of treatment – 1. Induction chemotherapy – 2. Post-remission consolidation chemotherapy – 3. CNS prophylaxis (chemotherapy/radiation) – 4. Maintenance therapy

Treatment of Adult ALL • Age <65 vs. > 65 years old • Co-morbidities • Presence of Philadelphia chromosome (Ph + )

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

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

Multi-Agent Chemotherapy • Induction chemotherapy – Anthracycline (doxorubicin/daunorubicin) – Vincristine – Steroid (prednisone or dexamethasone) – Asparaginase (pegaspargase) – Cyclophosphamide – High dose methotrexate, cytarabine – Mercaptopurine

Treatment of ALL • Consolidation – Allogeneic transplant if donor available – Continue multi-agent chemotherapy • Plus TKI for Ph + – Corticosteroids • Plus TKI for Ph +