Aplastic Anemia

Question 1

Name 4 acquired conditions associated with Aplastic Anemia and their mechanism?

Answer 1

1) Fanconi Anemia (DNA damage response)
2) Diamond-Blackfan anemia (defective ribogenesis)
3) Dyskeratosis congenita (abnormal telomere dynamics)
4) Amegakaryocytic thrombocytopenia (altered hematopoietic growth factor receptor/kinase signaling)

Question 2

What are 3 catergories of Aplastic Anemia and how are they defined?

Answer 2

1) Moderate AA
2) Severe AA (BM < 30% cellularity, 2 lineages down)
3) Very severe AA (ANC < 200)

Question 3

What are typical cytogenetic findings in AA; if not typical what diagnosis would you consider

Answer 3

normal karyotype; if cytoegenetics have abnormalities than diagnosis is likely MDS.

Question 4

What condition is commonly confused with Aplastic Anemia and what feature on bone marrow examination helps distinguish the two diagnosis?

Answer 4

Hypocellular MDS

megakaryocytes are abberant or small mononuclear in MDS, whereas in AA they are less to absent.

Question 5

What diagnosis occurs concomitantly in 40-50% of cases?

Answer 5

Paroxsymal Noctural hemoglobinuria

Question 6

Whats the molecular issue in PNH?

Answer 6

mutated PIG gene encoding an anchoring membrane protein (glycosolphosphytidalinositol)

Question 7

What is the preferred source of matched donor stem cells for transplant?

Answer 7

bone marrow; has less incidence of GVHD

Question 8

What are two main stay options for treatment of AA? Which is preffered for patients < 40 years of age?
Efficacy?

Answer 8

allogeneic transplant (90%) and immunosuppresive therapy (70%)
allo

Question 9

What is preffered immunosuppresive therapy?

Answer 9

horse ATG (4 days) and cyclosporine (6 months)

Question 10

What immunosuppresive regimen can be used in salvage? Its comparative efficacy?

Answer 10

rabbit ATG (more lymphcytotoxic)
37% versus 68%

Question 11

What chemotherapuetic is equally effective to horse ATG, usedin 1990s. Why are we not using first line now?

Answer 11

Cyclophosphamide (200mg/kg). Increased rate of fungal infections and deaths.

Question 12

What are key things to remember with ATG administration

Answer 12

double lumen line
ATG test dose
Plts > 20
no B-blockers (suppresses physiologic compensatory response in anaphylaxis
40mg/kg over 4 hours daily for 4 days
Prednisone 1mg/kg

Question 13

What are main side effects with ATG tx and their tx?

Answer 13

fevers (tyelenol)
rigors (meperidine)
rash (benadryl)
hypotension (IV hydration)
hypoxemia (02)

Question 14

What conditions may patients develop with CsA tx and what do we use to treat it?

Answer 14

• HTn, amolodipine (no interaction) ; CCB contraindicated
• Gingival hyperplasia: azithromycin
• renal insufficeny (adjust CsA dosing and moniter AKI)

Question 15

What prophylaxis is recommended?

Answer 15

PCP with Pentamidine

Question 16

What type of response is favorable? And when does it occur?

Answer 16

Any response, can be seen between 2-3 months but improve over years.

Question 17

What guides management? blood counts or marrow

Answer 17

blood counts

Question 18

What helps you identify evolution?

Answer 18

marrow morphology & cytogenetics