AML

Question 1

Imaging if central nervous system (CNS) hemorrhage
suspected

Answer 1

Brain CT without contrast

Question 2

Imaging if leukemic meningitis suspected

Answer 2

Brain MRI with and without contrast

Question 3

Imaging in individuals with extramedullary disease

Answer 3

FDG-PET/CT

Question 4

Imaging to evaluate myocardial function in patients
with a history or symptoms of cardiac disease or prior/planned exposure to cardiotoxic drugs or radiation therapy (RT) to thorax

Answer 4

Echocardiogram or MUGA scan

Question 5

WBC count for Low risk APL

Answer 5

≤10 x 109/L

Question 6

TRUE OR FALSE

FLT3 inhibitors are not recommended for FLT3-positive APL.

Answer 6

TRUE

FLT3 inhibitors are not recommended for FLT3-positive APL.

Question 7

Used to manage high WBC count (>10 x 109/L) during induction with ATRA/arsenic trioxide

Answer 7

Hydroxyurea

Question 8

Preferred Regimen for Low-Risk APL Induction

Answer 8

ATRA/arsenic trioxide

• ATRA 45 mg/m2 in 2 divided doses daily + arsenic trioxide 0.15 mg/kg IV daily (category 1)
• 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 9

Preferred Regimen for Low-Risk APL Consolidation

Answer 9

Arsenic trioxide/ATRA

• Arsenic trioxideh 0.15 mg/kg/d IV 5 d/wk for 4 weeks every 8 weeks for a total of 4 cycles, and ATRA 45 mg/ m2/d for 2 weeks every 4 weeks for a total of 7 cycles (category 1)

Question 10

Low-Risk APL

Useful in Certain Circumstances (if arsenic is not available or contraindicated)

Answer 10

Induction: ATRA/idarubicin;
Consolidation: ATRA/idarubicin, then ATRA/mitoxantrone, then ATRA/idarubicin

Induction: ATRA/gemtuzumab ozogamicin
Consolidation: ATRA/gemtuzumab ozogamicin

Induction:
* ATRA 45 mg/m2 in 2 divided doses daily + idarubicin 12 mg/
m2 on days 2, 4, 6, 8 (category 1) or on days 2, 4, 6 for aged >70 y
* ATRA 45 mg/m2 in 2 divided doses daily + a single dose of
gemtuzumab ozogamicin 9 mg/ m2 on day 5

Consolidation
ATRA 45 mg/m2 x 15 days + idarubicin 5 mg/m2 x 4 days x 1 cycle,
then ATRA x 15 days + mitoxantrone 10 mg/m2/d x 3 days x 1
cycle, then ATRA x 15 days + idarubicin 12 mg/m2 x 1 day x 1 cycle
(category 1)

Question 11

Preferred Regimen for High-Risk APL Induction and Consolidation

Answer 11

Induction: ATRA/idarubicin/arsenic trioxide;
Consolidation: ATRA/arsenic trioxide

Induction: ATRA/arsenic trioxide/gemtuzumab ozogamicin;
Consolidation: Arsenic trioxide/ATRA

Induction: ATRA/arsenic trioxide/gemtuzumab ozogamicin;
Consolidation: Gemtuzumab ozogamicin (if ATRA/arsenic trioxide discontinued due to toxicity)

Question 12

Regimen for High-Risk APL with Cardiac Issue: Low-Ejection Fraction

Answer 12

Induction: ATRA/arsenic trioxide/gemtuzumab ozogamicin;
Consolidation: Arsenic trioxide/ATRA

Induction: ATRA/arsenic trioxide/gemtuzumab ozogamicin;
Consolidation: Gemtuzumab ozogamicin (if ATRA/Arsenic trioxide discontinued due to toxicity)

No anthracyclibe

Question 13

Regimen for High-Risk APL with Cardiac Issue: Prolonged QTc

Answer 13

Induction: ATRA/gemtuzumab ozogamicin;
Consolidation: ATRA/gemtuzumab ozogamicin

Induction: ATRA/daunorubicin/cytarabine;
Consolidation: Daunorubicin/cytarabine, then cytarabine/daunorubicin/IT chemotherapy

Induction: ATRA/idarubicin;
Consolidation: ATRA/idarubicin/cytarabine, then ATRA/mitoxantrone, then ATRA/idarubicin/cytarabine

No ATO

Question 14

Test that should be performed on a blood sample at completion of consolidation to document molecular remission.

Answer 14

PCR

Question 15

PCR monitoring

In patients receiving the ATRA/arsenic regimen,
consider earlier sampling at ______ months during consolidation.

Answer 15

3–4 months during consolidation

Question 16

Prior practice guidelines have recommended monitoring blood by PCR every 3 mo for 2 y to
detect molecular relapse.

This is reccomended for patients with:

Answer 16

• High-risk disease
• Those >60 y of age
• Had long interruptions during consolidation
• Patients on regimens that use maintenance and are not able to tolerate maintenance

Question 17

To confirm PCR positivity, a second blood sample should be done in ___ weeks in a reliable laboratory

Answer 17

2–4 weeks

• If the second test is negative, frequent monitoring (every 3 mo for 2 y) is strongly recommended to confirm that the test remains negative.
• The PCR testing lab should indicate the level of sensitivity of assay for positivity (most clinical labs have a sensitivity level of 10-4)

Question 18

Management of clinical coagulopathy in APL

Targets

Answer 18

• Platelets ≥50 x 109/L
• Fibrinogen >150 mg/dL
• PT and PTT close to normal values

Monitor daily until coagulopathy resolves.

Question 19

TRUE OR FALSE

Leukapheresis is not routinely recommended in patients with a high WBC count in APL because of the difference in leukemia biology.

Answer 19

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 20

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

Answer 20

Differentiation Syndrome

Question 21

Management of Differentiation Syndrome

Answer 21

• 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 22

Prophylaxis for Differentiation Syndrome

Answer 22

Prednisone 0.5 mg/kg day or
Dexamethasone 10 mg every 12 h

Question 23

Treatment for leukocytosis associated with differentiation syndrome

Answer 23

• Hydroxyurea
• Anthracycline (daunorubicin or idarubicin) or Gemtuzumab ozogamicin

Question 24

Diagnostics prior to starting ATO

Answer 24

• ECG for prolonged QTc interval assessment
• Serum electrolytes (Ca, K, Mg, phosphorus) and creatinine

During therapy (weekly during induction therapy and before each course of post-remission therapy)

Question 25

Preferred Induction Regimen: **Favorable-Risk AML by Cytogenetics (CBF-AML)**

Answer 25

Cytarabine/Daunorubicin/Gemtuzumab ozogamicin Cytarabine/Idarubicin/Gemtuzumab ozogamicin ## Footnote Other recommended: 7 + 3 (mitoxantrone) - (for age ≥60 y)

Question 26

Preferred Induction Regimen: **Favorable-Risk AML by Mutation Profile (NPM1-mutated/FLT3 wild-type AML, in-frame bZIP mutation in CEBPA)** and **Intermediate-risk AML**

Answer 26

Cytarabine/Daunorubicin Cytarabine/Idarubicin Cytarabine/Mitoxantrone (for age ≥60 y)

Question 27

Induction Regimen: **AML with FLT3 mutation**

Answer 27

Cytarabine/Daunorubicin/Midostaurin Cytarabine/Idarubicin/Midostaurin Cytarabine/Daunorubicin/Quizartinib Cytarabine/Idarubicin/Quizartinib ## Footnote Walang preferred

Question 28

Preferred Induction Regimen: **Therapy-related AML other than CBF-AML; Antecedent MDS/CMML; AML-MRC**

Answer 28

CPX-351/dual-drug liposomal cytarabine and daunorubicin (≥60 years of age) Cytarabine/Daunorubicin (<60 years of age) Cytarabine/Idarubicin (<60 years of age)

Question 29

Induction Regimen: **Poor-Risk AML without TP53 Mutation or del17p Abnormality**

Answer 29

Cytarabine/Daunorubicin Cytarabine/Idarubicin CPX-351/dual-drug liposomal cytarabine and daunorubicin FLAG-IDA Decitabine (days 1–5)/Venetoclax Azacitidine/Venetoclax LDAC/Venetoclax ## Footnote *No regimens are considered preferred, clinical trial is recommended*

Question 30

Management of leukocytosis/leukostasis

Answer 30

* Leukapheresis * Hydroxyurea * Single dose of cytarabine ## Footnote Prompt institution of definitive therapy is essential.

Question 31

Patients who receive transplant shortly following **gemtuzumab ozogamicin** administration may be at risk for developing ________________________.

Answer 31

Sinusoidal obstruction syndrome (SOS)

Question 32

In times of fludarabine shortage, __________ can be substituted for fludarabine.

Answer 32

Cladribine

Question 33

# TRUE OR FALSE Gemtuzumab ozogamicin may be beneficial in NPM1-mutated AML and CEBPA-mutated AML.

Answer 33

FALSE Gemtuzumab ozogamicin may be beneficial in **NPM1-mutated** AML The role of gemtuzumab ozogamicin *in CEBPA-mutated AML is not established.*

Question 34

# TRUE OR FALSE While conventional induction chemotherapy regimens can be given in the setting of a TP53 mutation, less intensive chemotherapy is preferred for patients not enrolled in clinical trials.

Answer 34

TRUE While conventional induction chemotherapy regimens can be given in the setting of a TP53 mutation, **less intensive chemotherapy** is preferred for patients not enrolled in clinical trials. ## Footnote Outcomes for patients with **poor-risk AML with TP53 mutation** remain **poor with conventional induction chemotherapy.** The panel prioritizes **clinical trial enrollment** in this setting.

Question 35

When to perform follow-up BM aspirate and biopsy post induction

Answer 35

14–21 days after start of therapy ## Footnote When using a cytarabine-based induction regimen with doses of **cytarabine >100 to 200 mg/m2**, consider delaying BM aspirate and biopsy to **D21**.

Question 36

If there is ambiguous resut, repeat BM biopsy within ____ days before proceeding with therapy

Answer 36

7 days

Question 37

**Hypoplasia** is defined as:

Answer 37

Cellularity **less than 20%** of which the residual blasts are **less than 5%** (ie, blast percentage of residual cellularity).

Question 38

When to perform follow-up BM aspirate and biopsy post **re-induction**

Answer 38

* Upon count recovery, or * By **day 42** at the latest in the setting of delayed count recovery ## Footnote When performed, BM aspirate and biopsy should include cytogenetic and molecular studies, as appropriate. For measurable (minimal) residual disease (MRD) assessment

Question 39

Preferred Regimen: **LOWER INTENSITY THERAPY (INTENSIVE INDUCTION INELIGIBLE OR DECLINES)** **AML without IDH1 mutation**

Answer 39

* Azacitidine + venetoclax (category 1) * Decitabine + venetoclax

Question 40

Preferred Regimen: **LOWER INTENSITY THERAPY (INTENSIVE INDUCTION INELIGIBLE OR DECLINES)** **AML with IDH1 mutation**

Answer 40

* Azacitidine + venetoclax (category 1) * Azacitidine + ivosidenib (category 1)

Question 41

For patients who decline induction chemotherapy and/or targeted therapy, best supportive care may include:

Answer 41

Hydroxyurea and/or transfusion support

Question 42

Response to treatment with enasidenib or ivosidenib may take ____ months

Answer 42

3–5 months

Question 43

Criteria for patients eligible for the regimen **Azacitidine + ivosidenib** (IDH1-positive):

Answer 43

At least one of the following criteria: * Aged >75 years * Baseline ECOG performance status of 2 * Severe cardiac or pulmonary disease * Hepatic impairment with bilirubin >1.5 times the upper limit of normal * Creatinine clearance (CrCl) <45 mL/min, or * Other comorbidity

Question 44

Criteria for patients eligible for the regimen **LDAC + glasdegib**

Answer 44

* ≥75 years of age * Who have significant comorbid conditions (ie, severe cardiac disease, ECOG performance status ≥2, baseline creatinine >1.3 mg/dL) ## Footnote has been associated with an improved OS in a randomized trial

Question 45

**Allogeneic transplant** is recommended for patients with **favorable-risk** disease who are:

Answer 45

* Unable to complete consolidation * Who have high-risk features such as MRD-positivity or KIT mutation

Question 46

Who are eligible for maintenence therapy

Answer 46

**Patient with non-CBF-AML:** * Who received prior intensive chemotherapy and whose disease is now in remission * Completed no consolidation, some consolidation or a recommended course of consolidation * No allogeneic HCT is planned **Post allogeneic HCT, in remission, and history of FLT3 mutation** **Patient with history of FLT3-ITD mutation:** * Previously received quizartinib * No allogeneic HCT is planned

Question 47

Maintenence Therapy: **Patient with non-CBF-AML**

Answer 47

* **Oral azacitidine** until progression or unacceptable toxicity (category 1, preferred for age ≥55 y) * **HMA** until progression or unacceptable toxicity

Question 48

Maintenence Therapy: **Post allogeneic HCT, in remission, and history of FLT3 mutation**

Answer 48

* Sorafenib (FLT3-ITD only) * Midostaurin (FLT3-ITD or TKD) (category 2B) * Gilteritinib (FLT3-ITD or TKD) (category 2B) * Quizartinib (FLT3-ITD only) (category 2B)

Question 49

Maintenence Therapy: **Patient with history of FLT3-ITD mutation**

Answer 49

Quizartinib (FLT3-ITD only)

Question 50

# AML Surveillance CBC: BMA:

Answer 50

CBC: every 1–3 mo for 2 y, then every 3-6 mo up to 5 y BMA:only if peripheral smear is abnormal or cytopenias develop

Question 51

Initial successful induction regimen can be repeated if ______ months since induction regimen.

Answer 51

≥12 months

Question 52

Favorable Genetic Abnormality

Answer 52

* t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 * inv(16)(p13.1q22) or t(16;16) (p13.1;q22) /CBFB::MYH11 * Mutated NPM1 without FLT3-ITD * bZIP in-frame mutated CEBPAe

Question 53

Intermediate Genetic Abnormality

Answer 53

* Mutated NPM1 with FLT3-ITD * Wild-type NPM1 with FLT3-ITD (without adverse-risk genetic lesions) * t(9;11)(p21.3;q23.3)/MLLT3::KMT2A * Cytogenetic and/or molecular abnormalities not classified as favorable or adverse

Question 54

Poor/Adverse Genetic Abnormality

Answer 54

* t(6;9)(p23.3;q34.1)/DEK::NUP214 * t(v;11q23.3)/KMT2A-rearranged * t(9;22)(q34.1;q11.2)/BCR::ABL1 * t(8;16)(p11.2;p13.3)/KAT6A::CREBBP * inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1) * t(3q26.2;v)/MECOM(EVI1)-rearranged * -5 or del(5q); -7; -17/abn(17p) * Complex karyotype, monosomal karyotype * Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 * Mutated TP53 ## Footnote While ELN requires a variant allele fraction of at least 10% to categorize TP53 mutation as poor/ adverse risk, *NCCN considers TP53 mutation as poor/adverse risk, regardless of variant allele fraction.*

Question 55

The next step if there is **positive mass effect or increased intracranial pressure** on imaging

Answer 55

Consider **fine-needle aspiration (FNA) or biopsy** ## Footnote Do not perform LP

Question 56

Management if LP positive by morphology or immunotype by flow cytometry

Answer 56

IT chemotherapy 2x/wk until clear, then weekly x 4–6 wks ## Footnote **Induction chemotherapy should be started concurrently.** However, for patients receiving **HiDAC**, since this agent **crosses the blood brain barrier**, *IT therapy can be deferred until induction is completed*. IT chemotherapy may consist of **methotrexate, cytarabine, or a combination** of these agents.

Question 57

Management if **positive mass effect or increased intracranial pressure**

Answer 57

* RT followed by IT chemotherapyf 2x/wk until clear, then weekly x 4–6 wks or * HiDAC-based therapy + dexamethasone to reduce intracranial pressure ## Footnote Concurrent use of CNS RT with HiDAC or IT methotrexate may increase risk of neurotoxicity

Question 58

**Screening LP** should be considered at **first remission before first consolidation** for patients with:

Answer 58

* Monocytic differentiation * MPAL * WBC count >40 x 109/L at diagnosis * Extramedullary disease * High-risk APL * FLT3 mutations

Question 59

Management of patients who present with **isolated extramedullary disease (myeloid sarcoma)**

Answer 59

Systemic therapy ## Footnote **Local therapy (RT or surgery [rare cases]**) may be used for **residual disease or for symptomatic disease**.

Question 60

# Transfusion thresholds: Hemoglobin: Platelets:

Answer 60

Hemoglobin: **≤7 to 8 g/dL or per institutional guidelines or symptoms of anemia** Platelets: **< 10,000/mcL or with any signs of bleeding** ## Footnote * **Leukocyte-depleted** products should be used for transfusion * Patients who are **alloimmunized** should receive **cross-match–compatible and/or HLA-specific** blood products

Question 61

Tumor lysis prophylaxis:

Answer 61

* Hydration with diuresis * Allopurinol or rasburicase

Question 62

Should be considered as initial treatment in patients with rapidly increasing blast counts, high uric acid, or evidence of impaired renal function

Answer 62

Rasburicase ## Footnote **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** should be checked

Question 63

**Neurologic assessment**, including tests for nystagmus, slurred speech, and dysmetria, should be performed before each dose of cytarabine especially on:

Answer 63

* Patients receiving HiDAC therapy (particularly those with impaired renal function), or * Intermediate-dose cytarabine in patients >60 years of age

Question 64

# TRUE OR FALSE In patients who develop cerebellar toxicity, cytarabine should be stopped and rechallenged thereafter.

Answer 64

FALSE In patients who develop **cerebellar toxicity**, cytarabine should be **stopped**. ## Footnote ***Rechallenge with HiDAC in future treatment cycles should not be attempted.***

Question 65

Steroid eye drops should be administered to both eyes **4 times daily** for all patients undergoing **HiDAC** therapy until _____ hours post completion of cytarabine.

Answer 65

24 hours

Question 66

Patients should be off granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF for a minimum of ____ days before obtaining BM to document remission.

Answer 66

7 days

Question 67

________________ has been shown to significantly decrease fungal infections when compared to fluconazole and itraconazole.

Answer 67

Posaconazole

Question 68

# Monitoring during Induction therapy CBC:

Answer 68

* **Daily or as clinically indicated** during chemotherapy and * **Every other day** after recovery of ANC >0.5 x 109/L until either normal differential or persistent leukemia is documented

Question 69

# Monitoring during Induction therapy Platelet:

Answer 69

**Daily** while in the hospital **until platelet-transfusion independent**

Question 70

# Monitoring during Induction therapy Chemistry profile, including electrolytes, liver function tests (LFTs), blood urea nitrogen (BUN), creatinine, uric acid, and phosphorous:

Answer 70

**Daily** during active treatment until **risk of tumor lysis is past**

Question 71

# Monitoring during Induction therapy LFTs:

Answer 71

1–2 x/wk

Question 72

# Monitoring during Induction therapy Coagulation panel:

Answer 72

1–2 x/wk DIC: daily

Question 73

# Monitoring Post-Remission Therapy During chemotherapy: CBC, platelets: Chemistry profile:

Answer 73

During chemotherapy: CBC, platelets: **2x/wk** Chemistry profile: **daily**

Question 74

# Monitoring Post-Remission Therapy Outpatient monitoring post chemotherapy: CBC, platelets, differential, and electrolytes:

Answer 74

Outpatient monitoring post chemotherapy: CBC, platelets, differential, and electrolytes: **2–3 x/wk until recovery**

Question 75

The most frequently employed methods for MRD assessment

Answer 75

Real-time quantitative PCR (RQ-PCR) assays (ie, NPM1,2 CBFB::MYH11, RUNX1::RUNX1T13) and Multicolor flow cytometry (MFC) assays ## Footnote *NGS–based assays to detect mutated genes (targeted sequencing, 20–50 genes per panel) is **not** routinely used, as the sensitivity of **PCR-based assays and flow cytometry is superior** to what is achieved by conventional NGS.*

Question 76

Timing of MRD assessment:

Answer 76

* Upon completion of initial induction * Before allogeneic HCT ## Footnote Additional time points should be guided by the regimen used

Question 77

# RESPONSE CRITERIA DEFINITIONS Morphologic leukemia-free state (MLFS)

Answer 77

* BM **<5%** blasts in an aspirate with spicules; at least **200** cells must be enumerated * No blasts with Auer rods or persistence of extramedullary disease ## Footnote * If there is a question of residual leukemia, a BM aspirate/biopsy should be repeated in **one week**. * A BM biopsy/aspirate should be performed.

Question 78

# RESPONSE CRITERIA DEFINITIONS Complete response (CR)

Answer 78

* Morphologic CR – transfusion independence * ANC ≥1 x 109/L (blasts <5%) * Platelets ≥100 x 109/L (blasts <5%)

Question 79

# RESPONSE CRITERIA DEFINITIONS CR with partial hematologic recovery (CRh)

Answer 79

* <5% blasts in the BM, no evidence of disease (NED) * Partial recovery of peripheral blood counts (**platelets >50 × 109/L** and **ANC ≥0.5 × 109/L**)

Question 80

# RESPONSE CRITERIA DEFINITIONS CR with incomplete hematologic recovery (CRi)

Answer 80

All CR criteria and transfusion independence but with persistence of **neutropenia (<1 x 109/L)** or **thrombocytopenia (<100 x 109/L)**

Question 81

# RESPONSE CRITERIA DEFINITIONS Partial remission (PR)

Answer 81

Decrease of **at least 50%** in the percentage of blasts to **5% to 25%** in the BM aspirate and the **normalization of blood counts**

Question 82

# RESPONSE CRITERIA DEFINITIONS Relapse following CR

Answer 82

* Reappearance of leukemic blasts in the peripheral blood or * Finding of more than 5% blasts in the BM, not attributable to another cause (eg, BM regeneration after consolidation therapy) or * Extramedullary relapse

Question 83

# RESPONSE CRITERIA DEFINITIONS Lack of response to induction

Answer 83

Inability to attain CR or CRi following exposure to **at least 2 courses** of intensive induction therapy

Question 84

# THERAPY FOR RELAPSED/REFRACTORY DISEASE Targeted therapy: **Therapy for AML with FLT3-ITD mutation** **Therapy for AML with FLT3-TKD mutation** **Therapy for AML with IDH2 mutation** **Therapy for AML with IDH1 mutation** **Therapy for CD33-positive AML**

Answer 84

Targeted therapy: **Therapy for AML with FLT3-ITD mutation** * Gilteritinib (category 1) * HMAs (azacitidine or decitabine) + sorafenib * Quizartinib (category 2B) **Therapy for AML with FLT3-TKD mutation** * Gilteritinib (category 1) **Therapy for AML with IDH2 mutation** * Enasidenib **Therapy for AML with IDH1 mutation** * Ivosidenib * Olutasidenib **Therapy for CD33-positive AML** * Gemtuzumab ozogamicin

Question 85

# THERAPY FOR RELAPSED/REFRACTORY DISEASE Aggressive therapy for appropriate patients:

Answer 85

* Cladribine + cytarabine + G-CSF ± mitoxantrone or idarubicin * Cytarabine ± (idarubicin or daunorubicin or mitoxantrone) * Fludarabine + cytarabine + G-CSF ± idarubicin * Etoposide + cytarabine ± mitoxantrone * Clofarabine ± cytarabine ± idarubicin

Question 86

# THERAPY FOR RELAPSED/REFRACTORY DISEASE Less aggressive therapy:

Answer 86

* HMAs (azacitidine or decitabine) * LDAC (category 2B) * (HMA or LDAC) + venetoclax

Question 87

Potential drug interactions with Venetoclax

Answer 87

* **Strong CYP3A4 inhibitors** (especially **posaconazole**) require significant **dose reductions** during initiation and ramp-up phase followed by a reduced daily dose. * The use of **strong or moderate CYP3A4 inducers** (eg, carbamazepine, phenytoin, rifampin) should be **avoided**.

Question 88

Prior to Venetoclax therapy it is important to decrease the risk of severe tumor lysis syndrome (TLS), aim to achieve WBC count of ___________ x 109/L with hydroxyurea/leukapheresis if necessary.

Answer 88

WBC count of <25 x 109/L

Question 89

Intrapatient dose escalation for venetoclax with HMA: Intrapatient dose escalation for venetoclax with LDAC:

Answer 89

Intrapatient dose escalation for venetoclax with HMA: **100 mg, 200 mg, and 400 mg daily on days 1–3** Intrapatient dose escalation for venetoclax with LDAC: **100 mg, 200 mg, 400 mg, and 600 mg daily on days 1–4** ## Footnote * Recommend treatment with allopurinol or other uric acid lowering agent until no further risk of TLS. * For patients with proliferative disease, monitor blood chemistries every 6–8 hours after initiation; if within normal limits, recheck once daily and continue monitoring until no further risk of TLS. * Aggressively monitor and manage electrolyte imbalances.

Question 90

# TRUE OR FALSE In Venetoclax use with HMA or LDAC Continue treatment regardless of cytopenias; transfuse as needed and no growth factors until treatment cycle is complete.

Answer 90

TRUE In Venetoclax use with HMA or LDAC **Continue treatment regardless of cytopenias**; transfuse as needed and **no growth factors** until treatment cycle is complete.

Question 91

BM biopsy for response assessment on days _______

Answer 91

Days 21–28 ## Footnote * If **no morphologic remission** (persistent BM blasts above 5%) but evidence of efficacy exists, **proceed with a second cycle without interruption** with the goal of achieving morphologic remission, and repeat BM biopsy on days 21–28 of this cycle.

Question 92

A disorder of immature dendritic cells that regulate effector T-cell function Most commonly presents as asymptomatic skin lesions, cytopenias, circulating peripheral blasts (leukemic phase), lymphadenopathy, and CNS manifestations. It constitutes only **0.44%** of hematologic malignancies and **< 1%** of acute leukemia presentations Median age, 65–67 years Male-to-female ratio of 3:1

Answer 92

Blastic Plasmacytoid Dendritic Cell Neoplasm

Question 93

Prognosis for BPDCN is poor and the median OS is approximately ________ months when patients are treated with chemotherapy.

Answer 93

8–12 months

Question 94

BPDCN diagnosis requires at least **4** of 6 BPDCN antigens:

Answer 94

* CD123 * CD4 * CD56 * TCL-1 * CD2AP * CD303/BDCA-2 ## Footnote Without myeloid T or B lineage expression markers

Question 95

Preferred Induction Regimen for BPDCN A CD123-targeted therapy

Answer 95

**Tagraxofusp-erzs** (formerly SL-401) 12 mcg/kg IV over 15 minutes once daily on days 1–5 of a 21-day cycle7 Alternately, 5 doses can be administered over a 10-day period, if needed for dose delays. ## Footnote IT chemotherapy in patients with documented CNS disease at diagnosis/ if clinically indicated (methotrexate, cytarabine)

Question 96

*Patients with low performance and/or nutritional status* Options for Localized/isolated cutaneous disease

Answer 96

* Surgical excision * Focal RT

Question 97

*Patients with low performance and/or nutritional status* Options for Systemic disease (palliative intent)

Answer 97

* Venetoclax-based therapy * Systemic steroids * Supportive Care

Question 98

Potentially serious adverse events associated with tagraxofusp-erzs treatment

Answer 98

Hypoalbuminemia and capillary leak syndrome ## Footnote **A decrease in serum albumin during the first days of treatment** seems to be the most consistent predictor of capillary leak syndrome.

Question 99

Patients must have a baseline serum albumin of __________ to be able to start tagraxofusp-erzs.

Answer 99

3.2 g/dL or higher ## Footnote Replace serum albumin if <3.5 g/dL or if there is a reduction of ≥0.5 from baseline.

Question 100

Hold Tagraxofusp-erzs Dosing for the Following Reasons:

Answer 100

* Serum albumin <3.5 g/dL or a reduction from baseline of ≥0.5 * Body weight ≥1.5 kg over prior day * Edema, fluid overload, and/or hypotension * Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) increase >5 times the upper limit of normal * Serum creatinine >1.8 or CrCl ≤60 mL/min * Systolic blood pressure (SBP) ≥160 or ≤80 mmHg * Heart rate (HR) ≥130 bpm or ≤40 bpm * Temperature ≥38°C * Mild to severe hypersensitivity reaction

Question 101

The rate of therapy-related MDS/AML is higher among patients with certain primary tumors:

Answer 101

* Breast cancer * Gynecologic cancers * Lymphomas (both non-Hodgkin lymphoma and Hodgkin lymphoma)

Question 102

Two well-documented categories of cytotoxic agents associated with the development of therapy-related MDS/AML:

Answer 102

* Alkylating agents * Topoisomerase inhibitors

Question 103

Clinical outcomes in patients with **therapy-related AML** have been shown to be significantly **inferior** (both in terms of relapse-free survival [RFS] and overall survival [OS]) compared with patients with de novo cases except those with:

Answer 103

* Therapy-related acute promyelocytic leukemia (APL) subtype or * The favorable-risk core binding factor (CBF) translocations

Question 104

Attributes of therapy-related APL (t-APL)

Answer 104

* 1) the average age of diagnosis is 47 years with a higher incidence in females * 2) the risk significantly declines 2 years after completion of treatment for the primary antecedent disease; * 3) breast cancer, hematologic malignancy, multiple sclerosis, and genitourinary malignancy are the most common antecedent diseases; * 4) topoisomerase II inhibitors and RT have the highest risk associated with developing t-APL; * 5) the clinicopathology of t-APL is not different from de novo APL; * 6) the single mutation t(15;17) is most common; and * 7) the remission rate of t-APL is 80%, which is comparable to de novo APL ## Footnote Therefore, t-APL and de novo APL are treated similarly.

Question 105

Anthracycline with longer intracellular retention time

Answer 105

Idarubicin

Question 106

A humanized anti-CD33 monoclonal antibody conjugated with the cytotoxic agent calicheamicin

Answer 106

GO