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Acute Leukemia. David Lee, MD, FRCPC. Overview. Concepts, biology Epidemiology Clinical and laboratory manifestations Diagnosis Management and prognosis. Classification of leukemias. Acute. Chronic. Myeloid origin. Acute Myeloid Leukemia (AML). Chronic Myeloid Leukemia (CML).

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acute leukemia

Acute Leukemia

David Lee, MD, FRCPC

overview
Overview
  • Concepts, biology
  • Epidemiology
  • Clinical and laboratory manifestations
  • Diagnosis
  • Management and prognosis
classification of leukemias
Classification of leukemias

Acute

Chronic

Myeloid origin

Acute Myeloid Leukemia (AML)

Chronic Myeloid Leukemia (CML)

Lymphoid origin

Acute Lymphoblastic Leukemia (ALL)

Chronic Lymphocytic Leukemia (CLL)

slide4

ALL

naïve

germinal center

B-lymphocytes

Plasma

cells

Lymphoid

progenitor

T-lymphocytes

Neutrophils

AML

Myeloid

progenitor

Eosinophils

Hematopoietic

stem cell

Basophils

Monocytes

Platelets

Red cells

myeloid maturation

myeloblast

promyelocyte

myelocyte

metamyelocyte

band

neutrophil

Myeloid maturation

MATURATION

Adapted and modified from U Va website

acute leukemia6
Acute Leukemia
  • accumulation of blasts in the marrow
how to distinguish aml vs cml from looking at peripheral blood
How to distinguish AML vs CMLfrom looking at peripheral blood

Myeloid cell CML AML normal

blasts qq

promyelocytes q

myelocytes q

metamyelocytes q

bands q

neutrophils q # q

significance of adult acute leukemia
Significance of adult acute leukemia
  • a hematologic urgency
  • usually fatal within weeks to months without chemotherapy
  • with treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia)
  • notify Hematologist promptly if acute leukemia is suspected
classification of acute leukemias
ALL

mainly children

M > F

curable in 70% of children

curable in minority of adults

AML

mainly adults

M > F

curable in minority of adults

Classification of acute leukemias
two hit model of leukemogenesis
Two-hit model of leukemogenesis

Loss of function of transcription factors needed for differentiation

eg. AML1-ETO

CBFb-SMMHC

PML-RARa

Gain of function mutations of tyrosine kinases

eg. FLT3, c-KIT mutations

N- and K-RAS mutations

BCR-ABL

TEL-PDGFbR

differentiation

block

enhanced

proliferation

Acute

Leukemia

+

causes of acute leukemias
Causes of acute leukemias
  • idiopathic (most)
  • underlying hematologic disorders
  • chemicals, drugs
  • ionizing radiation
  • viruses (HTLV I)
  • hereditary/genetic conditions
clincal manifestations
Clincal manifestations
  • symptoms due to:
    • marrow failure
    • tissue infiltration
    • leukostasis
    • constitutional symptoms
    • other (DIC)
  • usually short duration of symptoms
marrow failure
Marrow failure
  • neutropenia: infections, sepsis
  • anemia: fatigue, pallor
  • thrombocytopenia: bleeding
infiltration of tissues organs
Infiltration of tissues/organs
  • enlargement of liver, spleen, lymph nodes
  • gum hypertrophy
  • bone pain
  • other organs: CNS, skin, testis, any organ
chloromas

A

B

C

Chloromas

NEJM 1998

leukostasis
Leukostasis
  • accumulation of blasts in microcirculation with impaired perfusion
  • lungs: hypoxemia, pulmonary infiltrates
  • CNS: stroke
  • only seen with WBC >> 50 x 109/L
constitutional symptoms
Constitutional symptoms
  • fever and sweats common
  • weight loss less common
laboratory features
Laboratory features
  • WBC usually elevated, but can be normal or low
  • blasts in peripheral blood
  • normocytic anemia
  • thrombocytopenia
  • neutropenia
  • DIC
bone marrow in acute leukemia
Bone marrow in acute leukemia
  • necessary for diagnosis
  • useful for determining type
  • useful for prognosis
  • Acute leukemias are defined by the presence of > 20% blasts in bone marrow (% of nucleated marrow cells)
distinguishing aml from all
Distinguishing AML from ALL
  • light microscopy
    • AML: Auer rods, cytoplasmic granules
    • ALL: no Auer rods or granules.
  • flow cytometry
  • special stains (cytochemistry)
treatment of acute leukemias
Treatment of acute leukemias

Choice of Rx is influenced by:

  • type (AML vs ALL)
  • age
  • curative vs palliative intent
principles of treatment
Principles of treatment
  • combination chemotherapy
    • first goal is complete remission
    • further Rx to prevent relapse
  • supportive medical care
    • transfusions, antibiotics, nutrition
  • psychosocial support
    • patient and family
chemotherapy for acute leukemias
Chemotherapy for acute leukemias
  • Phases of ALL treatment
    • induction
    • intensification
    • CNS prophylaxis
    • maintenance
  • Phases of AML treatment
    • induction
    • consolidation (post-remission therapy)

post-remission therapy

hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation
  • permits “rescue” from otherwise excessively toxic treatment
  • additional advantage of graft-vs-leukemia effect in allogeneic transplants
  • trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic
prognosis
Prognosis

Adult AML

Adult ALL

similar to or worse than AML

overview31
Overview
  • Concepts, biology
  • Epidemiology
  • Clinical and laboratory manifestations
  • Diagnosis
  • Management and prognosis