Acute and Chronic Leukemias

Question 1

Myelogenous Leukemias

Answer 1

Acute Myelogenous Leukemia (AML)
Gazillion subtypes

Chronic Myelogenous Leukemia (CML

Question 2

Lymphocytic/ Lymphoblastic Leukemias

Answer 2

Acute Lymphoblasic Leukemia (ALL)
B cell
T cell

Chronic Lymphocytic Leukemia (CLL)

Hairy Cell Leukemia

Adult T cell Leukemia
HTLV-1

Question 3

Leukemias by age

Answer 3

0- adolescent (0-14):  ALL
Adolescent to adult (15-59):  AML
Adult(40-60+):  AML/CML
Elderly adult (>60):  CLL

Question 4

Acute Myelogenous Leukemia

Answer 4

Young to middle aged adults

Maturational arrest in granulocyte development, leading to proliferation of malignant precursor cells

Question 5

Clinical features of AML

Answer 5

EVIDENCE OF MARROW FAILURE
Anemia
Thrombocytopenia
Neutropenia
Leukocytosis with ↑↑ blasts
diffuse bone marrow infiltration

Auer rods can be present

Question 6

Signs and symptoms of AML

Answer 6

Fatigue
Bleeding/ecchymoses
DIC (APL)
Gum infiltration (monocytic)

Question 7

Acute Promyelocytic Leukemia

Answer 7

Corresponds to FAB M3 
WHO APML with t(15;17)(q22;q12)- TRANSLOCATION 15:17
5-8% of AML
Any age, but usually 3-5 decades of life
Frequently presents with DIC
Rapid doubling time
Often has large numbers of Auer rods

Question 8

Acute Promyelocytic Leukemia treatment and prognosis

Answer 8

Treat with ATRA and alkylating agent

80-90% remission

Question 9

Acute Monocytic Leukemia

Answer 9

Auer rods are rare
GUM INFILTRATION is frequently the presenting sign
Diagnosis hinges on immunophenotype (CD markers)

Question 10

Chronic Myelogenous Leukemia

Answer 10

15% of adult leukemias
May be related to radiation or benzene
Pluripotent
t(9;22) BCR-ABL fusion gene … aka Philadelphia chromosome
Protracted chronic phase, sometimes many years, followed by BLAST CRISIS

Question 11

Philadelphia Chromosome

Answer 11

De novo mutation

NOT specific for CML

BCR-ABL1 fusion gene produces a constitutively ACTIVE TYROSINE KINASE, leading to dysregulation of proliferation and normal apoptosis

Question 12

Chronic Myelogenous Leukemia Clinical Features

Answer 12

WBC >5x109/L
Characteristic diff, with FULL SPECTRUM OF GRANULOCYTES REPRESENTED 
<10% BLASTS
Fever, night sweats, weight loss
Splenomegaly
Bleeding/ecchymoses

Question 13

What is blast crisis

Answer 13

Progression to acute leukemia

> 20% blasts

Large aggregates in BM and extramedullary tissue

Usually fatal

Question 14

CML treatment and prognosis

Answer 14

The prognosis depends on response to TKI’s (e.g. imatinib; aka Gleevec)

With allogenic stem cell transplant, 5-year progression-free survival 80-95%

Question 15

B Cell Acute Lymphoblastic Leukemia

Answer 15

Most common leukemia in children
80-85% of ALL are B-cell
75% of cases involve children under 6 yo
Primitive, undifferentiated lymphoblasts
Express CD10, tdt (flow cytometry)

Question 16

Differentiating CML from Leukemoid reaction

Answer 16

Leukocyte Alkaline phosphatase is low in CML and high in Leukemoid reaction

Question 17

Clinical Features of B cell Acute Lymphoblastic Leukemia

Answer 17

Marrow failure: anemia, thrombocytopenia, neutropenia
WBC can be low, normal, or extremely high
Extramedullary involvement common in CNS, LN, spleen, liver, testis

Question 18

B cell ALL prognosis (and favorable factors)

Answer 18

90-95% complete remission
FAVORABLE FACTORS: 
age 1-10 
t(12;22)/ETV-RUNX1
Hyperdiploidy (>52 chromosomes)

Question 19

T cell Acute Lymphoblastic Leukemia

Answer 19

Frequently presents with mediastinal mass or acute leukemia
15-20% of childhood leukemias
CD10-, tdt+

Question 20

Chronic Lymphocytic Leukemia

Answer 20

Clonal B cell neoplasm – light chain restricted (kappa vs lambda)
OVERALL, MOST COMMON HUMAN LEUKEMIA
Most common LA in elderly
Mature, virgin B-cells (CD19+,CD20+); blasts <10%
Aberrant co-expression of CD5 and CD23

Question 21

Chronic Lymphcytic Leukemia clinical features

Answer 21

WBC 10-100 x 109/L
Small mature lymphs
Clumped chromatin
Smudge cells
Lymphoid aggregates in bone marrow

Question 22

Prognosis of CLL- which genes are favorable and unfavorable

Answer 22

Mutated IGVH (FAVORABLE): median survival 293 months

ZAP-70 and CD38 expression are UNFAVORABLE

2-8% develop DLBCL (Richter Transformation) – median survival <1 yr

Indolent disease – treatment usually withheld, but Chlorambucil if treatment is warranted

Question 23

Hairy Cell Leukemia

Answer 23

Neoplasm of memory B cells
Older Caucasian males
Indolent disease
Pancytopenia, monocytopenia*
Splenomegaly
CD11c, CD25, CD103

Question 24

Clinical Finding in Hairy Cell Leukemia

Answer 24

Frequent splenic red pulp sequestration – splenomegaly
Diffuse bone marrow involvement – fried egg appearance
Dense reticulin network – “dry tap”

Question 25

Adult T cell Leukemia

Answer 25

CD4+ T cell neoplasm caused by HTLV-1
Floret, or "clover leaf" cells
LA, hepatosplenomegaly, lymphocytosis
Rapidly progressive and fatal within 1 yr
Endemic to:
Japan
West Africa
Caribean