Hemepath Acute Leukemia Lecture

Question 1

Main flow lineage marker for T-ALL

Answer 1

cytoplasmic CD3

Question 2

AML Lineage defining markers on flow

Answer 2

NSE
CD11c
CD11b
CD14
CD64
Lysozyme

Question 3

Gold standard for blast counting for diagnosis of an acute leukemia

Answer 3

Aspirate or periperal blood smear counting by morphology

Flow, while great, has a lot of technical problems that make the exact numbers subject to variability:

Were erythroids lysed?
How was the gate drawn?
Is the immunophenotype of the blasts consistent and readily identifiable?

Question 4

Day 14 marrow goal

Answer 4

Marrow ablation

Less than 10% marrow cellularity, small minority of blasts

Question 5

Day 30 marrow goal

Answer 5

Remission

Count recovery and less than 5% marrow blasts with no circulating blasts.

Question 6

Relapse in leukemia

Answer 6

Defined as new development of >5% blasts in a marrow after having previously achieved remission.

Question 7

Persistent disease in leukemia

Answer 7

Defined as >5% blasts in a marrow without having every achieved remission.

Question 8

Minimal residual disease in leukemia

Answer 8

Defined as having less than 5% blasts in marrow, but detectable malignant disease below the level of 5% by NGS, flow, or PCR.

Question 9

HLA-DR negative AML should make you think. . .

Answer 9

APML

Question 10

To define CEBPA-mutated AML, . . .

Answer 10

. . . both copies of CEBPA must be mutated

Question 11

NPM1 and FLT3 mutation interplay

Answer 11

On its own, NPM1 mutation in AML are a favorable prognostic factor.

However, if it co-occurs with a FLT3 mutation, the prognosis is much poorer. These are the subtypes that have the characteristic cup-like nuclear invagination morphology, which is NOT seen in simple NPM1-mutated AML.

Question 12

Ways to diagnose MDS with myelodysplasia-related changes

Answer 12

Any prior diagnosis of MDS or MDS-MPN

An MDS-associated cytogenetic abnormality

Severe morphologic dysplasia (>50% of cells are dysplastic in at least 2 lineages)

Question 13

“Therapy-related MDS/AML”

Answer 13

In the setting of therapy-associated myeloid neoplasia, the prognostic differences between MDS and AML collapse. The blast percentage is no longer predictive.

Thus, some just refer to this as “Therapy-related MDS/AML” to drive this point home.

Question 14

Alkylating-agent associated AMLs

Answer 14

Latency of 5-7 years

Often preceded by a period of MDS

Karotype often complex with loss of 5 and 7

Question 15

Topoisomerase II inhibitor and anthracycline-associated AMLs

Answer 15

Shorter latency period of ~3 years, often associated with KMT2A rearrangements.

More simple cytogenetics

Question 16

Atypical monocyte features by flow

Answer 16

Aberrant expression of CD56
Decreased expression of HLA-DR
Decreased expression of CD14