Paediatrics

Question 1

Transient abnormal myelopoiesis (TAM)

Answer 1

Confirmation of constitutional **trisomy 21  **

PB leucocytosis with increased blasts 

Detection of exon 2/3 GATA1 mutation (GATA1 exon 2/3 sequencing should be performed in all cases with PB blasts >10%) 

 

Question 2

Myeloid leukemia of Down Syndrome

Answer 2

Confirmation of** constitutional trisomy 21  **

Myeloid neoplasm with persistent/increased PB and/or BM blasts (may be <20%) 

“in individuals with Down syndrome, there are no biologic differences between MDS and AML, hence the term ‘myeloid leukaemia of Down syndrome’ encompasses both MDS and AML 

Detection of exon 2/3 GATA1 mutation

Desirable: 
* Mutation profiling and detection of mutation in other genes, e.g. cohesin complex, EZH2, KANSL1 and/or JAK3 

Question 3

Epidemiology of TAM

Answer 3

TAM presents <6 months and usually within **1st week of life.  **

Neonates acquire GATA1 mutation PRIOR to birth

25-30% of newborns with DS have a GATA1 mutation 
* 10% have clinical manifestations 
* 15% have silent TAM (no clinical or haematologic features) 

Most (>90%) cases of **TAM spontaneously remit within 3 months  **

In 20-30% of cases of TAM, non-remitting AMKL develops within 1-3 years 

NO clinical, haematological or molecular features reliably predict which TAM cases develop ML-DS

Question 4

Age of presentation of Myeloid Leukemia of DS

Answer 4

Almost always present < 4 years of age.

AML in children > 4y.o with DW is rare and may represent unrelated AML (cases without GATA1 mutations, and should be considered conventional MDS or AML)

Question 5

FBE and morph findings in TAM

Answer 5

Patients < 7 days old

FBE + film
- leucocytosis with increased blasts
- >blasts are myeloblasts and megakaryoblasts
- variable platelet count, megakaryocyte fragments
- normal Hb (mostly)

IF evidence of end organ dysfunction – hepatosplenomegaly, pleural effusion, skin invovlement = ML-DS

Don’t need to flow, but blasts will have megakaryoblastic immunophenotype