Chapter 35

Acute Leukemias

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc.

 Chapter Overview

 Classification schemes for acute leukemia

 Acute lymphoblastic leukemia
 Acute myeloid leukemia
 Acute leukemias of ambiguous lineage
 Future directions in the classification of acute
leukemias
 Cytochemical stains and interpretations

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 2

 Classification Schemes for Acute
Leukemias
 French-American-British (FAB)
 1970s
 Morphologic examination
 Cytochemical stains
 Myeloblasts versus lymphoblasts

 World Health Organization (WHO)

 2001, 2008
 Recurring chromosomal and genetic lesions
 At least 20% blasts in bone marrow

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 3

 Acute Lymphoblastic Leukemia (ALL)
 Incidence
 Clinical features
 B-cell ALL
• Fatigue, fever, mucocutaneous bleeding
• Lymphadenopathy, splenomegaly, hepatomegaly
• Bone pain
• Infiltration of malignant cells
• CNS involvement
 T-cell ALL
• Large mass in mediastinum
• Anemia, thrombocytopenia
• Organomegaly
• Bone pain
Continued
Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 4
Acute Lymphoblastic Leukemia (Cont.)

 World Health Organization Classification

 B lymphoblastic leukemia/lymphoma—7 subtypes
associated with recurrent genetic abnormalities
 T lymphoblastic leukemia/lymphoma—not subdivided
clinically
 Morphology
 Lymphoblast
• Small (1.0-2.5 times the size of normal lymphocyte)
• Larger ( 2-3 times the size of a normal lymphocyte)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 5

Acute Lymphoblastic Leukemia (Cont.)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 6

Acute Lymphoblastic Leukemia (Cont.)

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 7

Acute Lymphoblastic Leukemia (Cont.)

 Prognosis
 Age
 Lymphoblast load
 Immunophenotype
 Genetic abnormalities
 Hepatosplenomegaly
 Lymphadenopathy

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 8

Acute Lymphoblastic Leukemia (Cont.)

 Immunophenotyping
 B and T cells express CD34, TdT, HLA-DR
 B-ALL: CD19, CD20, CD22, CD24, C79a, CD10,
cytoplasmic µ, PAX-5
 T-ALL: CD2, CD3, CD4, CD5, CD7, CD8
 Four Types of ALL
• Early B-ALL (pro-B or pre-pre B)
• Intermediate (common) B-ALL
• Pre-B ALL
• T-ALL

Continued
Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 9
Acute Lymphoblastic Leukemia (Cont.)

 Genetic and Molecular Findings:

 T-ALL
• NOTCH1
 B lymphoblastic leukemia/lymphoma
• t(9;22) (q34;q11.2); BCR-ABL1
• t(v;11q23); MLL
• t(12;21)(p13;q22); ETV6-RUNX1
• Hyperdiploidy
• Hypodiploidy

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 10

 Acute Myeloid Leukemia (AML)

 Incidence
 Clinical Presentation
 Pallor, fatigue, bruising, bleeding, fever
 DIC
 Malignant cell infiltration
 Splenomegaly
 Tumor lysis syndrome
• Breakdown of dying cancer cells
• Acute uric acid nephropathy, renal failure

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 11

 Acute Myeloid Leukemia (Cont.)

 Laboratory findings
 Hyperuricemia
 Hyperphosphatemia
 Hypocalcemia
 Hypokalemia

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 12

 Acute Myeloid Leukemia (Cont.)

 Diagnosis
 Complete blood count
• WBC: increased, decreased, or normal
• Anemia, thrombocytopenia
 Peripheral blood smear examination
• Myeloblasts
 Bone marrow aspirate and biopsy examination
• Hypercellular
• >20% blasts
 Genetic abnormalities

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 13

 Acute Myeloid Leukemia (Cont.)
 AML with Recurrent Genetic Abnormalities:
 AML with t(8;21)(q22;q22); RUNX1/RUNX1T1
 AML with inv(16)(p13.1q22) or t(16;16)(p13.1:q22);
CBFB-MYH11
 AML with t(15;17)(q22:q12);PML-RARA
 AML with t(9;11)(p22;q23);MLLT3-MLL
 AML with t(6;9)(p23;q34);DEK-NUP214
 AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2);RPN1-
EV11
 AML (megakaryoblastic) with
t(1;22)(p13;q13);RBM15-MKL-1

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 14

 AML with
t(8;21)(q22;q22);RUNX1/RUNXT1

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 15

 AML with inv(16)(p13.1q22) or
t(16;16)(p13.1;q22);CBFB-MYH11

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis,
2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 16

AML with t(15;17);PML-RARA

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis,
2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 17

 AML with
t(9;11) (p22’q23);MLLT3-MLL

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 18

 Acute Myeloid Leukemia (Cont.)

 Acute myeloid leukemia with myelodysplasia-

related changes
 Incidence
 Laboratory features
 Therapy-related myeloid neoplasms
 Incidence
 Laboratory features

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 19

 Acute Myeloid Leukemia (Cont.)

 Acute myeloid leukemia, not otherwise specified

 Acute myeloid leukemia with minimal differentiation
 Acute myeloid leukemia without maturation
 Acute myeloid leukemia with maturation
 Acute myelomonocytic leukemia
 Acute monoblastic and monocytic leukemias
 Acute erythroid leukemia
 Acute megakaryoblastic leukemia

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 20

Acute Myeloid Leukemia with Minimal
Differentiation

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St.

Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 21

Acute Myeloid Leukemia Without
Maturation

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 22

Acute Myeloid Leukemia with
Maturation

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 23

Acute Myelomonocytic Leukemia

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 24

Acute Monoblastic and Monocytic
Leukemias

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4,

St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 25

Acute Erythroid Leukemia

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 26

Acute Megakaryoblastic Leukemia

From Carr JH, Rodak BF: Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 27

 Acute Myeloid Leukemia (Cont.)

 Myeloid sarcoma
 Myeloid proliferations related to down syndrome
 Blastic plasmacytoid dendritic cell neoplasm

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 28

 Acute Leukemias of Ambiguous
Lineage
 Acute undifferentiated leukemias (AULs)
 Mixed phenotype acute leukemias (MPALs)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 29

 Future Directions in the Classification
of Acute Leukemias
 Gene mutations—prognostic importance
 KIT
 FLT3
 ASXL1
 TP53
 CEBPA
 NPM1

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 30

 Cytochemical Stains

 Older techniques
 Low cost
 Performed worldwide
 Myeloperoxidase (MPO)
 Sudan black B (SBB)
 Esterases

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 31

Myeloperoxidase (MPO) (Cont.)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 32

Myeloperoxidase (MPO)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 33

Sudan Black B (SBB)

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 34

 Esterases

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 35

 Esterases

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 36

 Chapter Review

 What are the two categories the acute leukemias

can be divided into?
 What is the prognosis for childhood ALL versus
adult ALL?
 Using immunophenotyping, what are the four
categories of ALL?
 What is the incidence of ALL versus AML?
 What is the clinical presentation of a patient with
AML versus a patient with ALL?

Copyright © 2016, 2015, 2012 by Saunders, an imprint of Elsevier Inc. 37