Bone Marrow Failure 2 Flashcards
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?
Aplastic anemia
What classifies very severe AA?
BM cellularity <25%
ANC <200
What classifies severe AA (any 2 of 3)
BM cellularity <25%
ANC <500
platelets <20k
Reticulocytes <1% corrected or <60k
What classifies nonsevere AA?
BM cellularity <25% without any criteria of severe.
so, ANC above 500, platelet above 20k, reticulocyte above 1% or above 60k
Treatment for nonsevere AA?
Immunosuppression vs observation
Treatment for severe AA in patients under age 40 and matched sibling donor
Straight to alloHCT
Treatment for severe AA, age 41-60
ATG + cyclosporine + eltrombopag
If no response at 6 months, go to BMT
What’s the difference between horse and rabbit ATG?
Horse ATG is better for RR and OS
Side effects of ATG? (2)
anaphylaxis
serum sickness
Side effects of cyclosporine (4)
hirsutism
gingival hyperplasia
Kidney dysfunction
HTN
What supportive care is given prior to and during immunosuppression for acquired aplastic anemia?
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
What are distinguishing BM features of hypocellular MDS?
> 10% BM cellularity, excess blasts, multilineage dysplasia, ringed sideroblasts, fibrosis, copy # abnormalities in Chr5 and Chr7
Pathophysiology of PNH
Acquired mutation in PIGA gene causing loss of GPI anchored cell surface proteins
4 Treatment options for PNH
Eculizumab
Ravulizumab
Pegcetacoplan
Iptacopan
Danicopan (added on to Ecu or Ravu)
If PNH is coexistant with AA, when do you consider PNH-specific treatment?
When PNH clone is >50%, but oftentimes treating the AA with immunosuppression is sufficient.
-If above 50%, can try anticoagulation or eculizumab
Clinical manifestations of Fanconi Anemia
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
What needs to be considered for survivorship of patients with Fanconi Anemia?
Increased malignancy screening, particularly for H&N cancer and GU tract cancer
What special considerations need to be made for patients with Fanconi Anemia diagnosed with AML or MDS?
They are highly sensitive to chemotherapy + radiation
How to make the diagnosis of Fanconi Anemia?
Chromosome breakage in lymphocytes when WBCs are exposed to mitomycin or other DNA crosslinkers
What treatment can improve blood counts in patients with Fanconi Anemia?
Danazol
Clinical features of Dyskeratosis Congenita (AKA short telomere syndromes)
Widely variable phenotype
Dyskeratotic nails, leukoplakia of tongue, reticular rash, skin hypertrophy on hands/feet
Short stature, developmental delay, periodontal disease
What are long-term clinical consequences of Dyskeratosis congenita?
Pulmonary fibrosis
Liver disease
Esophageal stenosis
Periodontal disease
AVN
What is a special consideration for patients with Dyskeratosis congenita diagnosed with MDS or AML?
Hypersensitive to radiation/chemotherapy
What are the commonly implicated genes in Dyskeratosis congenita?
TERC, TERT, DKC1
How to make a diagnosis of Dyskeratosis Congenita?
Lymphocyte telomere length testing
Genetic testing
What are special survivorship needs for patients with Dyskeratosis Congenita?
Increased cancer screening, particularly H&N (>1000x risk), derm, anorectal
Clinical and lab features of Diamond-Blackfan Anemia
High MCV, low reticulocyte, elevated RBC deaminase
Elevated HbF
Short stature
Thumb abnormalities
Craniofacial defects
Cleft lip/palate
What cancers are patients with Diamond-Blackfan Anemia are at increased risk of?
AML
MDS
Female genital cancers
Osteogenic sarcoma
Pathogenesis of Diamond-Blackfan Anemia
Impaired ribosome function
Treatment for Diamond-Blackfan Anemia
Steroids get a response in 40%
If that doesn’t work, chronic transfusions
Clinical features of Schwachman-Diamond Syndrome
Bone marrow failure + exocrine pancreatic dysfunction
Skeletal deformities
Low serum trypsinogen or isoamylase, low fecal elastase
Mutation and mode of inheritance of Schwachman-Diamond Syndrome
AR mutation in SBDS
Clinical features of GATA2-related bone marrow failure
Variable phenotype, but aplastic anemia and combined immunodeficiency
