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Acute Leukemia Kristine Krafts, M.D.
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Hematologic Malignancies
Leukemia Malignancy of hematopoietic cells Starts in bone marrow, can spread to blood, nodes Myeloid or lymphoid Acute or chronic Lymphoma Starts in lymph nodes, can spread to blood, marrow Lymphoid only Hodgkin or non-Hodgkin
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Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias Lymphomas Hodgkin lymphoma Non-Hodgkin lymphoma Plasma cell disorders Multiple myeloma
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Hematologic Malignancies
Myeloid Lymphoid Acute myeloid leukemia Chronic myeloid leukemia Acute lymphoblastic leukemia Chronic lymphocytic leukemia Hodgkin lymphoma Non-Hodgkin lymphoma Multiple myeloma
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How is a diagnosis made? Clinical setting Morphology Immunophenotyping
Molecular studies Cytogenetics
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Bone marrow biopsy needle
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Bone marrow biopsy: cellularity
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Normal bone marrow biopsy
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Normal bone marrow biopsy
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Bone marrow aspiration needle
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Bone marrow aspiration
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Normal bone marrow aspirate
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Normal bone marrow aspirate
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Acute leukemias
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Chronic leukemias
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Non-Hodgkin lymphoma
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Hodgkin lymphoma
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Myeloma
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(Non-specific esterase)
Morphology Regular stain (Wright-Giemsa) Cytochemical stain (Non-specific esterase)
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Immunophenotyping
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Normal chromosomes Chromosomes in CML
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Cytogenetics
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Molecular Studies cut paste amplify
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Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias Lymphomas Hodgkin lymphoma Non-Hodgkin lymphoma Plasma cell disorders Multiple myeloma
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Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias
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Acute vs. chronic leukemia
Acute leukemia Sudden onset Can occur in either adults or children Rapidly fatal without treatment Composed of immature cells (blasts) Chronic leukemia Slow onset Occurs only in adults Longer course Composed of mature cells
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Acute ALL AML Chronic CLL CML Lymphoid Myeloid
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Acute ALL AML Chronic CLL CML
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Acute lymphoblastic leukemia Acute myeloid leukemia
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Chronic myeloid leukemia Chronic lymphocytic leukemia
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ALL AML CLL CML Lymphoid Myeloid
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Hematologic Malignancies
Leukemias Acute leukemias
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Pathophysiology of Acute Leukemia
Definition: malignant proliferation of immature myeloid or lymphoid cells in the bone marrow Cause Clonal expansion Maturation failure Badness Crowd out normal cells Inhibit normal cell function Infiltrate other organs
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Acute lymphoblastic leukemia Acute myeloid leukemia
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Acute leukemia: bone marrow biopsy
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Clinical Findings in Acute Leukemia
Sudden onset (days) Symptoms of bone marrow failure Fatigue Infections Bleeding Bone pain (expanding marrow) Organ infiltration (liver, spleen, brain)
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Laboratory Findings in Acute Leukemia
Blasts/immature cells in blood Leukocytosis Anemia Thrombocytopenia
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Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia
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Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia
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Acute Myeloid Leukemia
Things you must know Malignant proliferation of myeloid blasts in blood, bone marrow 20% cutoff for diagnosis Many subtypes Bad prognosis
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Acute Myeloid Leukemia
M0 - acute myeloblastic leukemia, minimally differentiated M1 - acute myeloblastic leukemia without maturation M2 - acute myeloblastic leukemia with maturation M3 - acute promyelocytic leukemia M4 - acute myelomonocytic leukemia M5 - acute monocytic leukemia M6 - acute erythroblastic leukemia M7 - acute megakaryoblastic leukemia
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Acute Myeloid Leukemia
involve neutrophilic series (myeloblasts, promyelocytes, etc.) involve monocytic series (monoblasts, etc.) involves erythroid series (erythroblasts) involves megakaryocytic series (megakaryoblasts)
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20% need at least blasts
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Acute myeloid leukemia: >20% blasts
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Acute myeloid leukemia: >20% blasts
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Acute myeloid leukemia
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AML-M3 (acute promyelocytic leukemia)
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AML-M6 (acute erythroblastic leukemia)
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AML-M5 (acute monoblastic leukemia)
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AML-M5: brain involvement
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AML-M5: brain involvement
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AML-M5: gum involvement
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before (L) and after (R) treatment
AML: gum involvement before (L) and after (R) treatment
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AML-M0: Acute myeloid leukemia without differentiation
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Auer rods
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Treatment and Prognosis of AML
Chemo Bone marrow transplant Prognosis Dismal Some chromosomal abnormalities convert different prognosis If therapy-related, worse prognosis
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Myelodysplastic Syndrome
Dysmyelopoiesis ± increased blasts May evolve into AML Older patients, usually Asymptomatic or marrow failure Macrocytic anemia Treatment depends on age, aggressiveness
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Dyserythropoiesis (dysmyelopoiesis in red cells)
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Dysgranulopoiesis (dysmyelopoiesis in neutrophils)
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Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia
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Acute Lymphoblastic Leukemia
Things You Must Know Malignant proliferation of lymphoid blasts in blood, bone marrow Classified by immunophenotype (B vs. T) More common in children Prognosis often good!
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ALL
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ALL
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ALL Immunophenotype T-lineage ALL: worse prognosis.
B-lineage ALL: better prognosis.
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children most common in
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Treatment and Prognosis of ALL
Chemo ± bone marrow transplant Many children are cured! Prognosis Immunophenotype (T is worse) Age (1-10 better) WBC (<10,000 better) Cytogenetics (hyperdiploidy better!)
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