CML

Question 1

CNL mutation

Answer 1

CSF3R

Question 2

immunophenotype of CML

Answer 2

CD10, CD19, CD20 (mature cell)

Question 3

accelerated phase CML criteria

Answer 3

1)10-19% blasts
2) *peripheral basophils >20%
3) platelet count <100k unrelated to treatment
4) additional chromosomal abnormalities (second Ph chromosome, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, or abnormalities of 3q26.2)

Question 4

Chromosomal abnormalities that meet criteria for accelerated phase CML

Answer 4

• second Ph chromosome
• trisomy 8
• isochromosome 17q
• trisomy 19
• complex karyotype
• abnormalities of 3q26.2

Question 5

Blast phase CML criteria

Answer 5

• 20% blasts
  *extramedullary disease (myeloid sarcoma)

Question 6

Rate of transformation from chronic phase to accelerated or blast phase annually

Answer 6

1% per year

Question 7

Class effects of BCR/ABL TKIs

Answer 7

• teratogenic
• myelosuppression
• periorbital edema

Question 8

imatinib SE’s

Answer 8

• edema
• hepatotoxic

Question 9

dasatinib SE’s

Answer 9

• pleural effusions
• pulmonary HTN
• QT prolongation
• cardiac dysfunction

Question 10

nilotinib SE’s

Answer 10

• QT prolongation (black box warning)
• hepatotoxic
• pancreatitis
• headache

Question 11

bosutinib SE’s

Answer 11

• diarrhea
• rash
• LFT elevation

Question 12

ponatinib SE

Answer 12

• arterial and venous thrombosis
• CHF
• hepatotoxic
• pancreatitis

Question 13

TReatment goals

Answer 13

• complete hematologic response at 3 months
• complete cytogenetic response at 6 months
• MMR at 12 months

Question 14

Criteria for TKI discontinuation

Answer 14

IF MMR AND age>18 AND Reliably taking TKI for ≥3 years AND No prior resistance to a second-generation (2G) TKI AND prior BCR/ABL transcript AND no accelerated phase history AND Stable molecular response (ie, MR4; BCR::ABL1 ≤0.01 percent by the International Scale [IS]) (table 1) for ≥2 years, as documented by ≥4 separate tests performed ≥3 months apart

Question 15

First line TKIs

Answer 15

Dasatinib
bosutinib
imatinib
NOT ponatinib (used second line for T3151 positive)

Question 16

CML in pregnancy

Answer 16

Pegylated interferon or leukapheresis

Question 17

Drug to use if Phe317Leu mutation
*classic mutation, high yield

Answer 17

Nilotinib

Question 18

Bosutinib resistance mutations

Answer 18

G250E
F317
V299L

Question 19

Dasatinib resistance mutations

Answer 19

F317
V299L

Question 20

Nilotinib resistance mutations

Answer 20

E255
Y253H
F359

Question 21

What is the goal PCR level at 3 months, 6 months, and 12 months?

Answer 21

<10% by 3 months
<1% by 6 months
<0.1% by 12 months

Question 22

significance of p190 BCR/ABL fusion protein

Answer 22

• less common fusion protein associated with high monocyte count

Question 23

Other dasatinib SE

Answer 23

• bleeding (GI bleeding

Question 24

Other nilotinib SE

Answer 24

• metabolic syndrome (hyperlipidemia + hyperglycemia)

Question 25

Dosing of 1) dasatinib 2) nilotinib 3) bosutinib 4) imatinib for accelerated phase *Need to know because accelerated phase requires higher doses

Answer 25

- imatinib 800 - nilotinib 400 BID - bosutinib 500 mg - dasatinib 140

Question 26

accelerated phase CML treatment

Answer 26

*Second generation TKIs as per above but consider higher dose followed by potential HSCT