IBMF Flashcards
What are the short and long term outcomes of HSCT versus immune therapy in aplastic anemia ?
Short-term survival with HLA-matched sibling transplant is comparable to that achieved with immune therapy
Long -term outcomes are
better with an incidence of late malignancy lower than that of the emergence of clonal
disease (AML, MDS, PNH) for transplant compared to immune therapy
Severe congenital neutropenia and malignancy risk.
severe congenital neutropenia (SCN or CN). Of the choices given, only ELANE (formerly known as ELA2) variants are associated with SCN or CN. SCN patients receiving G-CSF therapy require close marrow surveillance given the increased risk of developing MDS or AML. Development of acute myeloid leukemia (AML) with an acquired mutation in the cytoplasmic domain of the G-CSF receptor is commonly observed in patients with SCN after prolonged therapy with G-CSF. Additional acquired cytogenetic abnormalities include monosomy 7 and trisomy 21.
Nnormocytic red cell aplasia ( retic < 0.1%)
, the most common causes of which are Diamond-Blackfan anemia (DBA) and transient erythroblastopenia of childhood (TEC).
Gata 2 deficiency
The syndrome of monocytopenia, B cell lymphopenia, mycobacterial infections associated with predisposition to myelodysplasia and MDS is known as “MonoMAC” and is seen in patients with germline GATA2 deficiency.
GATA2 deficiency is a now recognized as a common germline, familial predisposition to pediatric MDS. Clinical presentation can range from asymptomatic to life-threatening infections, respiratory symptoms, lymphedema (Emberger syndrome) and cutaneous warts. Once a pathogenic GATA2 variant is identified, peripheral blood and marrow should be monitored given the substantial risk of progression to MDS or leukemia.
SMAD9 mutation
SAMD9 is associated with predisposition to pediatric MDS, its clinical phenotype presents as MIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy).
Pearson syndrome
Mitochondrial DNA deletions are found in Pearson syndrome, which typically present in infancy with transient cytopenias and with a life-threatening metabolic disorder.
ringed sideroblasts
WHIM
autosomal dominant mutations in CXCR4 cause a gain of function defect that results in a limitation of down regulation after stimulation.
neutropenia with warts, hypogammaglobulinemia, infections, and myelokathexis)
hypercellular marrow and retained myeloid cells with vacuolated cytoplasm
The combination of exocrine pancreatic insufficiency and otherwise idiopathic neutropenia is seen in
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Shwachman-Diamond syndrome, associated with mutations in the SBDS gene in the vast majority of cases
