NCCN AML

Question 1

Preferred induction regimens for low risk APL patients

Answer 1

1. ATRA 45 mg/m2 in 2 divided
   doses daily + arsenic trioxide
   0.15 mg/kg IV daily (category 1)

OR

2. ATRA 45 mg/m2 in 2 divided
   doses daily + arsenic trioxide
   0.3 mg/kg IV on days 1–5 of
   week 1 and 0.25 mg/kg twice
   weekly during weeks 2–8
   (category 1)

Question 2

Chemotherapy induction regimens for low risk APL patients if arsenic is not available or contraindicated

Answer 2

1. ATRA 45 mg/m2 in 2 divided
   doses daily + idarubicin 12 mg/
   m2 on days 2, 4, 6, 8k (category
   1) or on days 2, 4, 6 for aged
   >70 y

OR

2. ATRA 45 mg/m2 in 2 divided
   doses daily + a single dose of
   gemtuzumab ozogamicin 9 mg/
   m2 on day 5

Question 3

These interventions are important in safe administration of arsenic trioxide

Answer 3

QTc and monitoring and optimizing electrolytes are important in safe administration of arsenic trioxide. Electrocardiogram (ECG) is recommended prior to initiating arsenic trioxide.
During therapy, if a patient presents with a prolonged QT interval, the use
of QTcF correction formula is recommended.
Interventions such as minimizing concurrent QT-prolonging drugs and electrolyte correction are recommended prior to discontinuing arsenic trioxide.

Question 4

Management of clinical coagulopathy in APL

Answer 4

1. Aggressive platelet transfusion support to maintain platelets ≥50 x 109/L; fibrinogen replacement with
   cryoprecipitate and fresh frozen plasma to maintain a level >150 mg/dL and PT and PTT close to normal values. Monitor daily until coagulopathy resolves.
2. Avoid use of tunneled catheter or port-a-cath.

Question 5

TRUE OR FALSE
Leukapheresis is not routinely recommended in patients with a high WBC count in APL.

Answer 5

TRUE
Leukapheresis is not routinely recommended in patients with a high WBC count in APL because of the difference in leukemia biology; however, in life-threatening cases with leukostasis that is not responsive to other modalities, leukapheresis can be considered with caution.

Question 6

Symptoms for APL differentiation syndrome

Answer 6

Fever, often associated with increasing WBC count >10 x 109/L, usually at initial diagnosis or relapse; shortness of breath; hypoxemia; pleural or pericardial effusion

Question 7

Management of APL differentiation syndrome

Answer 7

Close monitoring of volume overload and pulmonary status is indicated. Initiate dexamethasone at first signs or symptoms of respiratory compromise (ie, hypoxemia, pulmonary infiltrates,
pericardial or pleural effusions) (10 mg BID for 3–5 days with a taper over 2 weeks).
Consider interrupting ATRA therapy until hypoxia resolves.

Question 8

Management for patients at high risk (WBC count >10 x 109/L) for developing differentiation syndrome

Answer 8

Initiate prophylaxis with corticosteroids, either prednisone 0.5 mg/kg day 1 or dexamethasone 10 mg every 12 h
Taper the steroid dose over a period of several days.
If patient develops differentiation syndrome, change prednisone to
dexamethasone 10 mg every 12 h until count recovery or risk of differentiation has abated.

Question 9

Treatment for leukocytosis associated with differentiation syndrome

Answer 9

Hydroxyurea can be used to treat leukocytosis associated with differentiation syndrome.
In difficult-to-treat cases, an anthracycline (daunorubicin
or idarubicin) or gemtuzumab ozogamicin can be used.

Question 10

Management prior to initiating arsenic trioxide therapy

Answer 10

Prior to initiating therapy:
◊ ECG for prolonged QTc interval assessment
◊ Serum electrolytes (Ca, K, Mg, phosphorus) and creatinine

Question 11

What is the next step if the patient’s disease is not in molecular remission (by quantitative PCR on BM sample) following the first cycle of consolidation of chemotherapy for APL?

Answer 11

Consider matched sibling or alternative donor (haploidentical, unrelated donor, or cord blood) HCT or clinical trial. Testing is recommended at least 2–3 weeks after the completion of arsenic trioxide to avoid false positives.

Question 12

Preferred induction treatment regimens for patients with high risk APL with cardiac issues

Answer 12

1. ATRA 45 mg/m2 (days 1–36, 2 divided
   doses daily) + age-adjusted idarubicin
   6–12 mg/m2 on days 2, 4, 6, 8 + arsenic
   trioxide 0.15 mg/kg (days 9–36 as 2 h IV
   infusion)

OR

2. ATRA 45 mg/m2 in 2 divided doses daily and arsenic trioxideh 0.15 mg/kg/d IV + a single dose of gemtuzumab ozogamicin 9 mg/m2 may be given on day 1, or day 2, or day 3, or day 4

OR

3. ATRA 45 mg/m2 in 2 divided doses daily and arsenic trioxide 0.3 mg/kg IV on days 1–5 of week 1 and 0.25 mg/kg twice weekly on weeks 2–8 (category 1) + a single dose of gemtuzumab ozogamicin 6 mg/m2 may be given on day 1, or day 2, or day 3, or day 4

Question 13

Other recommended induction treatment regimens for patients with high risk APL with cardiac issues

Answer 13

1. ATRA 45 mg/m2 in 2 divided doses daily + daunorubicin 50 mg/m2 x 4 days (IV days 3–6) + cytarabine 200 mg/m2 x 7 days (IV days 3–9)

OR

2. ATRA 45 mg/m2 in 2 divided doses daily + daunorubicin 60 mg/m2 x 3 days + cytarabine 200 mg/m2 x 7 days

OR

3. ATRA 45 mg/m2 in 2 divided doses daily + idarubicin 12 mg/m2 on days 2, 4, 6, 8 or on days 2, 4, 6 for those aged >70 y