Acute Leukemias

Question 1

What is the difference between an acute neoplasm and a chronic neoplasm?

Answer 1

Acute - presence of immature cells (Blasts)

Chronic- presence of differentiated (mature) cells

Both may be of either Lymphoid or Myeloid origin

Question 2

What is leukemia?

Answer 2

Malignant neoplasm characterized by the replacement of the bone marrow by neoplastic cells

Question 3

What is a lymphoma?

Answer 3

Proliferations of hematopoietic neoplasms arising as discrete tissue masses

Question 4

In general, what are some clinical features of acute leukemias?

Answer 4

Abrupt stormy onset
Suppression of normal hematopoiesis
Anemia - fatigue
Neutropenia - fever
Thrombocytopenia - bleeding

Question 5

What are some symptoms that are more likely to occur in ALL than AML?

Answer 5

ALL more likely to have generalized lymphadenopathy, splenomegaly, hepatomegaly, CNS involvement

Question 6

What acute leukemia are kids more likely to acquire?

Answer 6

ALL (80%)

Question 7

What are the neoplastic cells in ALL?

Answer 7

Lymphoblasts (B or T lymphoblasts)

85% of ALLs are pre-B cell neoplasms

Question 8

What are the special clinical features of T-ALL?

Answer 8

Commonly presents in adolescent males with thymic involvement

Presents as a mediastinal mass

Question 9

How is the diagnosis of ALL made?

Answer 9

Microscopic analysis -
See lymphoblasts with scant basophilic cytoplasm and fine nuclear chromatin

Flow cytometry for T and B cell markers

TdT test

Question 10

What is the specific stain used to diagnose ALL?

Answer 10

TdT
Terminal deoxynucleotidyl transferase
Positive in over 95% of ALLs

Question 11

What are some common chromosomal abnormalities with ALL?

Answer 11

Hyperdiploidy (over 50 chromosomes)

t(12;21) TEL-AML

t(9;22) - BCR-ABL; Philadelphia chromosome

t(4;11) (MLL gene)

Question 12

What is the general prognosis for ALL?

Answer 12

Complete remission rates of 90% or better in children

Cure in up to 2/3 patients

Question 13

What are some favorable prognostic indicators of ALL?

Answer 13

Age 2-10
Hyperdiploidy
TEL-AML t(12;21) mutation

Question 14

What are some unfavorable prognostic indicators of ALL?

Answer 14

Diagnosis before 2
Adolescent or adult presentation
Presence of t(9;22) (Philadelphia chromosome)

Question 15

Which leukemia are adults more likely to acquire?

Answer 15

AML (80%)

Question 16

AML is a highly heterogeneous disease. What cell types may AML involve?

Answer 16

Erythroblasts
Monoblasts
Megakaryoblasts
Myeloblasts

Question 17

What are some general causes of AML (the four main categories of WHO classification)?

Answer 17

1. AML with recurrent genetic abnormalities
2. AML arising from myelodysplastic syndrome
3. Therapy related
4. Not otherwise specified

Question 18

What are the two most important mutations associated with AML?

Answer 18

t(15;17) PML/RAR-alpha

t(11q23;v) MLL

Question 19

What is myelodysplastic syndrome (MDS)?

Answer 19

Pre-leukemic condition
Clonal stem cell disorder with defective and ineffective hematopoiesis with increased risk of transformation to AML

Could be idiopathic or therapy related (after chemo)

Question 20

Describe the pathophysiology of MDS

Answer 20

Hypercellular marrow with peripheral cytopenia
Cells are produced but they undergo apoptosis in the bone marrow itself, so they never make ti to the periphery

Could be cause by clonal cytogenetic abnormalities, stem cell damage, or morphologic abnormalities

Question 21

What are the morphological abnormalities associated with MDS?

Answer 21

Nuclear irregularity
Nuclear budding
Multinucleation
Separated nuclear lobes

Question 22

What is the prognosis of MDS?

Answer 22

Very bas
9-29 months for primary MDS, 4-8 months for secondary.

Subtypes of MDS with more blasts in the blood or marrow have a worse prognosis

Question 23

What are the clinical findings of AML?

Answer 23

Anemias
Cytopenias
Abrupt stormy onset
Not much tissue involvement
Lower chance of CNS involvement

Question 24

Acute Promyelocytic Leukemia (APL)

What mutation causes this disorder?

Answer 24

t(15;17)

Question 25

How is APL related to DIC?

Answer 25

Procoagulants (tissue factor) may be released by leukemic cells to induce DIC in APL patients

Question 26

What is the characteristic finding of APL on microscopic analysis?

Answer 26

Auer rods in the cytoplasm

Question 27

Describe the pathogenesis of APL

Answer 27

t(15;17)

Leads to an abnormal RAR-a receptor, which blocks myeloid differentiation

Question 28

What is the normal function of the RAR-alpha receptor?

Answer 28

Involved in activating the differentiation of myeloid cells

Question 29

How could you treat APL with a t(15;17) mutation?

Answer 29

High doses of All-trans-retinoic acid (vitamin A derivative) will overcome the block of the RAR-alpha receptor

Question 30

What two chemical stains may be used in the diagnosis of AML?

Answer 30

MPO

Alpha-naphthyl butyrate esterase

Question 31

What markers should be looked at on flow cytometry for suspected AML?

Answer 31

Myeloid markers
CD13
CD33
CD34
CD117

Question 32

What is an Auer rod? What does its presence tell you?

Answer 32

Auer rods are made of MPO which crystallizes and forms rod structures

Presence of Auer rod tells you it is a malignant myeloid cell

Question 33

What is the prognosis of AML?

Answer 33

Depends on the chromosome abnormality

t(15;17) and t(8;21) have good prognosis

MLL translocations have a poor outcome

AMLs arising from MDS or chemotherapy have very poor prognosis