Acute leukaemias & myelodysplastic syndromes

At diagnosis:

 

Disease subtype

 

Acute leukaemias

MDS; MDS/MPN

Morphology

Blast count

% of dysplasia per cell lineage, if AML

Maturation/differentiation, if AML

Blast count; monocyte count

% of dysplasia per cell lineage

Iron stain

Flow-cytometry

Acute leukaemia panel

Establish leukaemia associated immunophenotype (LAIP)

If childhood ALL: DNA index

If increased blasts on morphology

Markers of aberrant myeloid maturation

FISH

Recurrent translocations

Most frequent MDS related abnormalities

MDS panel

PDGFRA, PDGFRB and FGFR1 rearrangements if eosinophilia or other appropriate clinical picture

Karyotype

Recurrent translocations and other abnormalities

For IPSS

Molecular genetics

AML:

·       NPM1 exon 12 mutation

·       CEBPA mutation

·       FLT3 internal tandem duplication

·       FLT3 tyrosine kinase domain mutation

AML and ALL:

·       Appropriate fusion gene assessment by RT-PCR (when detected by FISH)

TP53 mutation (p53, on request)

Array CGH and/or next-generation sequencing panel (selected cases on discussion)

BM histology

Blast cell phenotype

Dysplasia

Dysplasia

Fibrosis

CD34/ CD117

 

At MRD*/ response evaluation**:

 

Disease subtype

 

Acute leukaemias

MDS; MDS/MPN

Morphology

* Blood counts

* Blast count

*Blood counts

*Blast count

Flow-cytometry

**ALL after 1st course

* AML if LAIP

N/A

FISH

* If marker present

N/A

Karyotype

N/A

N/A

Molecular genetics

The following markers of disease can be assessed:

·       Appropriate fusion gene by RT-PCR

·       NPM1 exon 12 mutation

N/A

BM histology

* Blast cell % if aspirate non-diagnostic

N/A

 

 

At relapse:

 

Disease subtype

 

Acute leukaemias

MDS; MDS/MPN

Morphology

Blast count

Dysplasia

Blast count

% of dysplasia per cell lineage

Flow-cytometry

Acute leukaemia panel

If blasts > 20%

FISH

If marker present

N/A

Karyotype

(Additional) abnormalities

If blasts > 20%

Molecular genetics

As for diagnosis

N/A

BM histology

Blast cell % if aspirate non-diagnostic

N/A

 

*MRD is used when morphological CR has to be monitored (repeatedly) with other, more sensitive techniques (e.g. cytogenetic CR or molecular CR)

 

**Response evaluation is used for investigation of the quality of clinical and morphological complete remission (after induction treatment) with more sensitive techniques e.g. as a prognostic marker.