Bone Marrow Failure Syndromes

Question 1

Bone marrow biopsy shows profoundly hypocellular, all elements decreased. Marrow space is mostly fat cells and stroma. Residual HSCs are morphologically normal. No infiltration of marrow with malignant cells or fibrosis. Diagnosis?

Answer 1

Aplastic anemia

Question 2

What classifies very severe AA?

Answer 2

BM cellularity <25%
ANC <200

Question 3

What classifies severe AA (any 2 of 3)

Answer 3

BM cellularity <25%
ANC <500
platelets <20k
Reticulocytes <1% corrected or <60k

Question 4

What classifies nonsevere AA?

Answer 4

BM cellularity <25% without any criteria of severe.
so, ANC above 500, platelet above 20k, reticulocyte above 1% or above 60k

Question 5

Treatment for nonsevere AA?

Answer 5

Immunosuppression vs observation

Question 6

Treatment for severe AA in patients under age 40 and matched sibling donor

Answer 6

Straight to alloHCT

Question 7

Treatment for severe AA, age 41-60

Answer 7

ATG + cyclosporine + eltrombopag
If no response at 6 months, go to BMT

Question 8

What’s the difference between horse and rabbit ATG?

Answer 8

Horse ATG is better for RR and OS

Question 9

Side effects of ATG? (2)

Answer 9

anaphylaxis
serum sickness

Question 10

Side effects of cyclosporine (4)

Answer 10

hirsutism
gingival hyperplasia
Kidney dysfunction
HTN

Question 11

What supportive care is given prior to and during immunosuppression for acquired aplastic anemia?

Answer 11

Antifungals if ANC <500
HSV prophylaxis x1 month
PCP prophylaxis for at least 3 months
G-CSF doesn’t have much benefit aside from reduction of hospitalization

Question 12

What are distinguishing BM features of hypocellular MDS?

Answer 12

> 10% BM cellularity, excess blasts, multilineage dysplasia, ringed sideroblasts, fibrosis, copy # abnormalities in Chr5 and Chr7

Question 13

Pathophysiology of PNH

Answer 13

Acquired mutation in PIGA gene causing loss of GPI anchored cell surface proteins

Question 14

4 Treatment options for PNH

Answer 14

Eculizumab
Ravulizumab
Pegcetacoplan
Iptacopan
Danicopan (added on to Ecu or Ravu)

Question 15

If PNH is coexistant with AA, when do you consider PNH-specific treatment?

Answer 15

When PNH clone is >50%, but oftentimes treating the AA with immunosuppression is sufficient.
-If above 50%, can try anticoagulation or eculizumab

Question 16

Clinical manifestations of Fanconi Anemia

Answer 16

Pancytopenia, predisposition to malignancy
Short stature (45%)
Microcephaly (20%)
Developmental delay (10%)
Cafe au lait spots (40%)
Thumb or radius abnormalities (35%)
Hypopigmentation
Hypogonadism, hypospadias

Question 17

What needs to be considered for survivorship of patients with Fanconi Anemia?

Answer 17

Increased malignancy screening, particularly for H&N cancer and GU tract cancer

Question 18

What special considerations need to be made for patients with Fanconi Anemia diagnosed with AML or MDS?

Answer 18

They are highly sensitive to chemotherapy + radiation

Question 19

How to make the diagnosis of Fanconi Anemia?

Answer 19

Chromosome breakage in lymphocytes when WBCs are exposed to mitomycin or other DNA crosslinkers

Question 20

What treatment can improve blood counts in patients with Fanconi Anemia?

Answer 20

Danazol

Question 21

Clinical features of Dyskeratosis Congenita (AKA short telomere syndromes)

Answer 21

Widely variable phenotype
Dyskeratotic nails, leukoplakia of tongue, reticular rash, skin hypertrophy on hands/feet
Short stature, developmental delay, periodontal disease

Question 22

What are long-term clinical consequences of Dyskeratosis congenita?

Answer 22

Pulmonary fibrosis
Liver disease
Esophageal stenosis
Periodontal disease
AVN

Question 22

What is a special consideration for patients with Dyskeratosis congenita diagnosed with MDS or AML?

Answer 22

Hypersensitive to radiation/chemotherapy

Question 22

What are the commonly implicated genes in Dyskeratosis congenita?

Answer 22

TERC, TERT, DKC1

Question 23

How to make a diagnosis of Dyskeratosis Congenita?

Answer 23

Lymphocyte telomere length testing
Genetic testing

Question 24

What are special survivorship needs for patients with Dyskeratosis Congenita?

Answer 24

Increased cancer screening, particularly H&N (>1000x risk), derm, anorectal

Question 25

Clinical and lab features of Diamond-Blackfan Anemia

Answer 25

High MCV, low reticulocyte, elevated RBC deaminase
Elevated HbF
Short stature
Thumb abnormalities
Craniofacial defects
Cleft lip/palate

Question 26

What cancers are patients with Diamond-Blackfan Anemia are at increased risk of?

Answer 26

AML
MDS
Female genital cancers
Osteogenic sarcoma

Question 27

Pathogenesis of Diamond-Blackfan Anemia

Answer 27

Impaired ribosome function

Question 28

Treatment for Diamond-Blackfan Anemia

Answer 28

Steroids get a response in 40%
If that doesn’t work, chronic transfusions

Question 29

Clinical features of Schwachman-Diamond Syndrome

Answer 29

Bone marrow failure + exocrine pancreatic dysfunction
Skeletal deformities
Low serum trypsinogen or isoamylase, low fecal elastase

Question 30

Mutation and mode of inheritance of Schwachman-Diamond Syndrome

Answer 30

AR mutation in SBDS

Question 31

Clinical features of GATA2-related bone marrow failure

Answer 31

Variable phenotype, but aplastic anemia and combined immunodeficiency