Intro to Leukemias and Myelomas

Question 1

Leukemia definition

Answer 1

Malignancy of hematopoietic cells arising in the bone marrow
The bone marrow is almost entirely replaced
Can be acute or chronic

Question 2

What is the difference between acute and chronic leukemia

Answer 2

Acute: all the cells are blasts
Chronic: the cells are more mature (might be some blasts, but a mix of other cells too)

Question 3

When you see high WBCs, what is the first question you ask?

Answer 3

What is the WBC differential?
# of blasts, neutrophils, and lymphocytes

Question 4

Acute myeloid leukemia (what is it, what pop is it more common in, how is it subclassified)

Answer 4

A myeloid malignancy arising in the bone marrow
All malignant cells are blasts
More common in adults over children
Subclassified by the mutations present

Question 5

Pathogenesis of acute leukemia

Answer 5

Begins with (usually idiopathic) mutations in a hematopoietic stem cell
Mutations lead to maturation arrest, immortality, and relentless cell division
Malignant blasts fill the marrow space and spill out into the peripheral blood
Leads to suppression of normal hematopoiesis, which causes cytopenias or pancytopenia

Question 6

Pancytopenia means you have what 3 problems

Answer 6

Anemic
Neutropenic
Thrombocytopenic

Question 7

If you see __ on a PBS, they definitely have AML

Answer 7

Auer rods

Red needle-like inclusion within the cytoplasm of some AML blasts

Question 8

If someone with AML is pancytopenic, what kind of symptoms can we expect to see from

1. Anemia
2. Neutropenia
3. Thrombocytopenia

Answer 8

1. Fatigue, pallor, SOB on exertion, palpitations, dizziness
2. Infections or fever
3. Bleeding with cuts, gum/nosebleeds, bruising, petechiae

Question 9

Clinical presentation of AML

Answer 9

Symptoms of pancytopenia
Constitutional symptoms (fever, night sweats, weight loss)
Some cases can trigger abnormal coagulation (DIC)

Question 10

Diagnosis of AML

Answer 10

Requires a bone marrow aspirate and biopsy

Special tests on the blasts to subclassify (flow cytometry, genetic tests)

Question 11

Is AML or ALL worse prognosis?

Answer 11

AML

Especially is worst the older the patient is or the more complex the genetic mutations are

Question 12

Acute lymphoid leukemia

Answer 12

A lymphoid malignancy arising in the bone marrow
All the malignant cells are blasts
More common in children (the most common malignant in children)
Begins with transforming mutations in a hematopoietic stem cells, making it malignant and trapping it in the blast stage
The transformed cell is lymphoid

Question 13

ALL diagnosis

Answer 13

Bone marrow aspirate and biopsy
Specialized tests (flow cytometry) can differentiate between B and T cell ALL
Genetic testing can identify specific mutations

Question 14

ALL clinical presentation

Answer 14

Symptoms of pancytopenia
Constitutional symptoms
May have palpable lymph nodes
CNS involvement is common (headaches, numbness - from cells in the CSF)
Prognosis is good in children, not as good in adults

Question 15

Chronic Myeloid Leukemia

Answer 15

Myeolid malignancy arising in the bone marrow
NOT all the malignant cells are blasts
Its a leukemia, and the most common myeloproliferative neoplasm
Malignant cells retain the capacity to mature past the blast cell stage
Chiefly a disease of adults
Basically every case has the Philadelphia chromosome (9;22)

Question 16

4 Myeloproliferative neoplasms

Answer 16

CML
Essential thrombocytosis
Polycythemia vera
Idiopathic myelofibrosis

Question 17

Therapy for CML

Answer 17

Targeted therapy with imatinib (Gleevac)

Because basically all cases have the philadelphia chromosome

Question 18

Left shift

Answer 18

There are a high number of young, immature WBCs present

Question 19

Classic age group for

1. AML
2. ALL
3. CML
4. CLL

Answer 19

1. Adults
2. Children
3. Adults
4. Elderly

Question 20

Chronic Lymphocytic Leukemia

Answer 20

A lymphoid malignancy
Arises in the bone marrow
Not all the malignant cells are blasts (mature lymphoid cells)
Older adults
Slowly progressive

Question 21

Difference between CLL and Small lymphocytic lymphoma (SLL)

Answer 21

CLL: primarily in bone marrow
SLL: primarily in lymph nodes

Question 22

How does CLL look on a PBS?

Answer 22

The cells look relatively normal
Lymphocyte counts may be very high though
Need special tests to prove they are malignant

Question 23

CLL clinical presentation

Answer 23

Often asymptomatic
Fatigue, weight loss, anorexia, splenomegaly
Very high lymphocyte counts
The malignant cells can spread to the nodes, so may have lymph node involvement
Cytopenias can take years to occur

Question 24

Multiple myeloma pathogenesis

Answer 24

Malignancy of plasma cells (lymphoid cells, but the final differentiation)
Secrete clonal immunoglobulin

Question 25

Characteristic morphology of multiple myeloma on PBS?

Answer 25

Paranuclear halo!

Eccentric nucleus

Question 26

Serum protein electrophoresis for multiple myeloma

Answer 26

Normally, the antibodies just look like a smear because there are a bunch of different types
In MM there is a massive overproduction of a single plasma cell
SPEP shows a single band representing the monoclonal antibody (M protein)

Question 27

Immunofixation for MM

Answer 27

Tells you what type of antibody it is

Monoclonal Abs can be an intact Ig, free light chains, or both

Question 28

In MM, what symptoms will you see in the bones?

Answer 28

Lytic lesions (malignant cells produce substances that promote bone trabeculae destruction)
Fractures (loss of bone)
Hypercalcemia (release of Ca from bone into blood)

Question 29

Clinical findings in MM: CRABi

Answer 29

C: calcium elevated from bone lysis
R: renal insufficiency (Igs and hypercalcemia damage kidney)
A: anemia (from marrow suppression and renal failure)
B: bone pain and pathological fractures (back pain presentation most common)
i: infections (suppressed normal Ab production)

Question 30

Prognosis and treatment for MM

Answer 30

Incurable (survival 7-10 years)
Reduction in monoclonal protein used to determine response
Treatment: Chemo and stem cell transplants