Leukemias (PDF)

Leukemias The “good”, the bad and the ugly  Leukemias Heterogeneous clonal hematopoietic progenitor and/or stem cell malignancy in which immature or mature hematopoietic cells proliferate and accumulate in the bone marrow, blood, and/or other tissues You can delete t...

Leukemias The “good”, the bad and the ugly  Leukemias Heterogeneous clonal hematopoietic progenitor and/or stem cell malignancy in which immature or mature hematopoietic cells proliferate and accumulate in the bone marrow, blood, and/or other tissues You can delete this slide when you’re done editing the presentation  Table of contents AML CLL Acute Myeloid Leukemia Chronic Lymphocytic Leukemia ALL CML Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia AML  AML 90% of all acute leukemias in adults, with an estimated 20,240 new cases and 11,400 deaths expected in the United States in 2021. Annual incidence is approximately 4.3 per 100,000 and increases with age, with approximately a 10-fold increased risk between the ages of 20 (1 case per 100,000) and 65 (1 case per 10,000) years. Median age at diagnosis is approximately 68 years, with approximately 6% of patients younger than 20 years and 34% of patients 75 years or older. Survival is highly dependent on age (~45% 5-year survival for patients aged 45, 65 yrs Median Age: 68 yrs Roughly 250 cases/year all-island 50 AML  AML Symptoms Pallor Fatigue Bone pain Hepatosplenomegaly Fever Bruising and bleeding. Tissue infiltration of the skin, gingiva, and central nervous system (CNS) is more common with monocytic subtypes AML  AML Diagnosis with BMAT Flow Cytometry Cytogenetics FISH Molecular analysis  AML French-American-British classification AML WHO vrs ICC  If defining genetic abnormality, then no blast requirement (unless BCR-ABL or CEBPA, where >20% AML needed) AML-NOS no longer exists: replaced by differentiation stage WHO vrs ICC  AML ELN Risk Favourable Intermediate Adverse t(8;21)(q22;q22.1)/RUNX1::RUNX1 Mutated NPM1 with FLT3-ITD t(6;9)(p23;q34.1)/DEK::NUP214 T1 Wild-type NPM1 with FLT3-ITD t(v;11q23.3)/KMT2A-rearranged inv(16)(p13.1q22) or t(9;11)(p21.3;q23.3)/MLLT3::KMT2A t(9;22)(q34.1;q11.2)/BCR::ABL1 t(16;16)(p13.1;q22)/CBFB::MYH11 Cytogenetic and/or molecular t(8;16)(p11;p13)/KAT6A::CREBBP Mutated NPM1 without FLT3-ITD abnormalities not classified as inv(3)(q21.3q26.2) or bZIP in-frame mutated CEBPA favorable or adverse t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1) t(3q26.2;v)/MECOM(EVI1)-rearranged −5 or del(5q); −7; −17/abn(17p) Complex karyotype, monosomal karyotype Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, or ZRSR2 Mutated TP53  Fit Unfit Induction Ongoing therapy with non intensive treatment Consolidation Palliative care Transplant or Maintenance  AML Young/Fit: Older/Less fit: Curative Intent Maximise survival/Maintain Quality of Life Induce Remission Disease Control Azacitidine DA 3 + 10: (Daunorubicin x 3d) + (Cytarabine x 10 d) Decitabine FLAG-Ida: Fludarabine + Cytarabine + G-CSF + Low-Dose Cytarabine Idarubicin +Venetoclax CR rate ~70% Adverse Cytogenetics: 47% CR rate ~30% Therapy-related AML: 51% Median OS 12m Secondary AML: 39%  AML EMA Drug Indication Approval Sep 2017 Midostaurin Adults with new diagnosis of AML, FLT3-mutated Apr 2018 Gemtuzumab Patients >15y with de novo CD33+ AML Ozogamicin Aug 2018 CPX-351 Newly-diagnosed t-AML / AML-MRC Oct 2019 Gilteritinib R/R AML with FLT-3 mutation Jun 2020 Glasdegib Newly-diagnosed AML unfit for intensive therapy May 2021 Venetoclax Newly-diagnosed AML unfit for intensive therapy Jun 2021 CC-486 Maintenance in adults in remission not undergoing HSCT Feb 2023 Ivosidenib Newly-diagnosed AML unfit for intensive therapy, IDH1m  APML Characterized by a balanced reciprocal translocation resulting in the fusion of the PML gene on chromosome 15 with the RARA gene on chromosome 17. 15% of all AMLs High CR rates  APML Coagulopathy causing early deaths with CNS and GI bleeds; major cause for treatment failure ASAP treatment with ATRA  APML Risk depends on WCC at presentation Management of differentiation syndrome and coagulopathy ATRA+ATO±anthracycline ALL  ALL Acute lymphoblastic leukemia (ALL) is the most common leukemia in children (representing 23% of all pediatric cancer diagnoses and 76% of leukemias among children