MDS/AML/ALL

Question 1

Based on Revised -IPSS
Very good karyotype 
Good karyotype
Poor karyotype
Very poor karyotype

Answer 1

Very good = -Y, def(11q)
Good = normal, del(5q), del(12p), del(20q), or double abnorm including del(5q)
Poor = -7, inv(3)/t(3q), double abnorm including -7/del(7q)
Very poor = complex karyotype (3 or more abnormalities)

Question 2

Lenalidomide in MDS

Answer 2

Indicated for low/interm-1 risk MDS with symptomatic or transfusion dependent anemia + del(5q) as sole cytogenetic abnormality

10mg lenalidomide daily

Question 3

ESAs in MDS

Answer 3

When EPO < 500

When Epo <100 and less than 2 transfusions per month – chance of responding to ESAs is 75%

Question 4

CMML

Answer 4

Overlap between MDS and MPN
MDS features (dysplasia, anemia, thrombocytopenia) and MPN features (leukocyosis, monocytosis, splenomegaly)

Characterized by absolute monocytosis 1000 or greater, persistent for > 3 months with no other etiology

Question 5

CCUS
ICUS
CHIP

Answer 5

CCUS: clonal cytopenias of undetermined significance
- unilineage or multilineage cytopenias and clonal hematopoeisis

ICUS: idiopathic cytopenias of undetermined significance
- unilineage or multilineage cytopenias and NO clonal hematopoeisis

CHIP: clonal hematopoesis of undetermined potential
- excludes clinically significant cytopenia but WITH evidence of clonal hematopoeisis

Question 6

When to use luspatarcept?

Answer 6

Luspatarcept – Approved for treatment of anemia failing ESA and requiring 2 or more RBC units over 8 weeks (2 months) in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with MDS/MPN with ring sideroblasts and thrombocytosis. MOA = recombinant fusion protein that binds transforming growth factor-beta ligands to reduce SMAD2 and SMAD3 signaling.

Question 7

Treatment of PV

Answer 7

Age <60 and no hx of thrombosis = aspirin + phlebotomy

If 
Age >60
Hx of thrombosis
Acquired VWD
Symptoms
 --> add HU

Use Rux instead of HU if inadequate response to HU

Question 8

Treatment of EV

Answer 8

Age <60 and no other risk factors = aspirin

If 
Age >60
Hx of thrombosis
Acquired VWD
Symptoms
 --> add HU

Question 9

APL high risk classification and treatment

Answer 9

WBC > 10

Give ATRA AND 7+3 (arsenic not needed)

Question 10

Chemotherapy agents causing AML/MDS - Time frame?

Answer 10

Topoisomerase inhibitors (including anthracyclines) - 1-2 yrs

Alkylating agents - longer, often with preceding MDS first

Question 11

Poor risk genetics for AML

Answer 11

t(6;9)
inv3
t(9;22); BCR-ABL1
FLT3 positive
ASXL1
RUNX1
TP53
MLL (11q23)
Complex or monosomal karyotype

Question 12

Good risk genetics for AML

Answer 12

t(15;17); PML-RARA
t(8;21)
Inv(16)
t(16;6)
Biallelic mutated CEBPA*
FLT3 negative
NPM1 mutation
With FLT3 negative/low
IDH2

Question 13

Poor risk genetic factors for ALL

Answer 13

Philadelphia chromosome
t(9;22)
Ph-Like
t(4;11) (KMT2A)
Complex cytogenetics
Hypoploidy

Question 14

CMV status ideal for transplant

Answer 14

CMV status is WORSE if recipient CMV+ and donor CMV- because then recipient could reactivate (as they have ab)

Question 15

Treatment for relapses B-ALL

Answer 15

These are for B (not T ALL)

Blinatumomab = Bi-specific T-cell Engager (BiTE), targets CD3/CD19
1st or 2nd remission with minimal residual disease

Inotuzumab = CD22+ antibody drug conjugate; carries chemotoxin calicheamicin

Clofarabine - Pts 1-21 with 2 or more prior therapies

CAR-T for young adults - Pts < 26 with refractory disease or 2 or more relapses

Question 16

What are ALL regimens

Answer 16

CALGB

• Peg-asparginase
• Vincristine
• Daunarubicin
• Pred
• IT MTX and IT cytarabine

HyperCVAD

• Cyclophosphamide
• Vincristine
• Doxorubicin
• Dex
• IT MTX and IT cytarabine

Question 17

Bilobed nucleus of neutrophils

Answer 17

Acquired Pseudo Pelger Huet abnormality - suggestive of MDS

Caused by mutations in LBR gene - inherited versus acquired

Acquired causes - called psuedo … due to meds - vpa, benzene, heme diseases, lupus