Aplastic Anemia

Question 1

What causes aplastic anemia?

Answer 1

Too few hematopoieic progenitor cells

Question 2

What does Acquired Aplastic Anemia need to be differentiated from?

Answer 2

Inherited bone marrow failure syndrome

Question 3

What causes the destruction of progenitors in bone marrow in SAA?

Answer 3

Assault by the T-cells

Question 4

What symptoms are associated with AA?

Answer 4

· Lethargy

· Epistaxis – Extended time

· Bacterial infections

Question 5

What triggers are for acquired SAA?

Answer 5

· Usually not identified

· Check for CMV, EBV, HHV-6, Parvovirus, Hepatitis

· History of jaundice

· Medication history – Chloramphenicol

· Exposures (Radiation/Nuclear)

Question 6

What is the Camitta Criteria?

Answer 6

Severe AA (SAA) “marked pancytopenia”

Peripheral Blood (2 of 3):

• < 500 PMN
• < 20,000 Platelets
• < 20,000

BM: 65% hypocellularity

Question 7

How is AA treated?

Answer 7

Matched Sibling BM

Intensive Immune Suppression with ATG/CSA/Prednisone

• Alemtuzumab
• Cyclophosphamide

Unrelated donor

Alternative, Alternative Donor BMT

• Halpo/Cord BMT; Double Cord BMT

Eltrombopag – TPO agonist, but also activates all erythroblasts

Question 8

What are telomeres?
What is the significance of their length?
What do mutations of telomerase cause?
What happens without telomerase?

Answer 8

Repeat sequences at ends of chromosomes

Molecular mechanisms have evolved to maintain telomere

Mutations in telomerase can result in marrow failure, liver fibrosis, lung firbrosis

Without telomerase, somolescence

Question 9

What is the classic disease of cancer biology?

Answer 9

Dyskeratosis Congenita

Question 10

What symptoms/findings are associated with Dyskeratosis Congenita?
What diagnostic parameters can be used to diagnose DC?
What is the treatment?

Answer 10

Leukoplakia, Lacy pigmentation, Abnormal finger and toe

Telomere length
Telomere length analysis is becoming a standard test
Genetic testing commercially available

Will need a transplant

Question 11

What is Fanconi Anemia caused by?
What special test must be done for it and why?
How is it treated?

Answer 11

DNA repair defect in Fanconi Gene

40% without physical stigmata so must do diagnostic/functional DEB test to look for chromosome
If DEB test abnormal, genetic testing to classify

Will need a transplant

Question 12

What is Schwachman-Diamond Syndrome?
What is it caused by?
What clinical findings are there?
What screening tests are there?

Answer 12

BM defect due to SBDS gene defect
Exocrine pancreatic deficiency and neutropenia
Isoamylase and trypsinogen are easily screening tests

Question 13

What is Diamond-Blackfan Anemia?
What is severe congenital neutropenia?

Answer 13

No RBCs
Lack of PMNs congenitally