Miscellaneous Hematology

Question 1

What is the brand name of Hydroxyurea?

Answer 1

The brand name of this generic drug is:
- Hydrea

Question 2

What is the brand name of All-Trans Retinoic Acid (ATRA, Tretinoin)?

Answer 2

The brand name of this generic drug is:
- Vesanoid

Question 3

What is the brand name of Arsenic Trioxide (ATO)?

Answer 3

The brand name of this generic drug is:
- Trisenox

Question 4

What is the generic of name of Hydrea?

Answer 4

The generic name of this brand name drug is:
- Hydroxyurea

Question 5

What is the generic of name of Vesanoid?

Answer 5

The generic name of this brand name drug is:
- All-Trans Retinoic Acid (ATRA, Tretinoin)

Question 6

What is the generic of name of Trisenox?

Answer 6

The generic name of this brand name drug is:
- Arsenic Trioxide (ATO)

Question 7

What is the MOA of Tretinoin?

Answer 7

This drug’s MOA is as follows:
- Binds one or more nuclear receptors and decreases proliferation and induces differentiation of APL cells

Question 8

What is the MOA of Arsenic Trioxide?

Answer 8

This drug’s MOA is as follows:
- Induces apoptosis in APL cells via DNA fragmentation and damages the fusion protein: promyelocytic leukemia (PML)-retinoic acid receptor (RAR) alpha

Question 9

What is the MOA of Hydroxyurea?

Answer 9

This drug’s MOA is as follows:
- Antimetabolite that selectively inhibits ribonucleoside diphosphate reductase and interferes with DNA repair.
- In sickle cell anemia, this drug increases hemoglobin F levels.

Question 10

What are the main indications for use of Hydroxyurea?

Answer 10

The main indications of this drug are:
- Cytoreduction in hematologic malignancies
- CML
- Head and Neck Cancer
- Sickle Cell Anemia
- Essential Thrombocythemia
- Polycythemia Vera

Question 11

What are the main indications for use of Arsenic Trioxide?

Answer 11

The main indications of this drug are:
- Acute Promyelocytic Leukemia

Question 12

What are the main indications for use of Tretinoin?

Answer 12

The main indications of this drug are:
- Acute Promyelocytic Leukemia

Question 13

What are the notable monitoring parameters for Tretinoin?

Answer 13

The notable monitoring parameters for this drug are:
- Confirm t(15:17) translocation or the presence of the PML/RAR-alpha fusion protein (confirming diagnosis of acute promyelocytic leukemia).
- Monitor patient multiple times daily during the initiation of therapy for signs of APL differentiation syndrome (monitor volume status, pulmonary status, temperature, respiration).
- Coagulation parameters at baseline then at least 2 to 3 times a week during induction and at least weekly during consolidation.
- Pregnancy test

Question 14

What are the notable monitoring parameters for Arsenic Trioxide?

Answer 14

The notable monitoring parameters for this drug are:
- Confirm t(15:17) translocation or the presence of the PML/RAR-alpha fusion protein (confirming diagnosis of acute promyelocytic leukemia).
- Monitor patient multiple times daily during the initiation of therapy for signs of APL differentiation syndrome (monitor volume status, pulmonary status, temperature, respiration).
- Coagulation parameters at baseline then at least 2 to 3 times a week during induction and at least weekly during consolidation.
- QTc via 12-lead EKG at baseline then weekly or twice weekly

Question 15

What are the notable monitoring parameters for Hydroxyurea?

Answer 15

The notable monitoring parameters for this drug are:
- CBC with differential and platelets (once weekly for antineoplastic indications, every 2 weeks initially for sickle cell anemia)

Question 16

What is the emetic potential of Hydroxyurea?

Answer 16

The emetic potential of this drug is:
- Minimal to Low

Question 17

What is the emetic potential of Tretinoin?

Answer 17

The emetic potential of this drug is:
- Minimal to Low

Question 18

What is the emetic potential of Arsenic Trioxide?

Answer 18

The emetic potential of this drug is:
- Low

Question 19

Describe the extravasation risk and management strategies for Hydroxyurea.

Answer 19

The extravasation risk and management strategies for this drug are as follows:
- None

Question 20

Describe the extravasation risk and management strategies for Tretinoin.

Answer 20

The extravasation risk and management strategies for this drug are as follows:
- None

Question 21

Describe the extravasation risk and management strategies for Arsenic Trioxide.

Answer 21

The extravasation risk and management strategies for this drug are as follows:
- None

Question 22

Describe the administration of Hydroxyurea.

Answer 22

The administration of this drug is described as follows:
- Hydroxyurea can be used for cytoreduction (urgently bringing down a high white blood cell count) in newly diagnosed hematologic malignancy patients or as maintenance therapy for patients with essential thrombocythemia, sickle cell disease, and chronic myeloid leukemia.
- Regardless of indication, doses are typically titrated to specific white blood cell or platelet counts (that vary depending on indication).
- When titrating doses for cytoreduction, doses are typically adjusted every few days.
- When used for maintenance indications, doses are typically titrated every few weeks.

Question 23

Describe the metabolism of Hydroxyurea.

Answer 23

The metabolism of this drug is as follows:
- Exposure is higher in patients with CrCl <60 mL/minute or end-stage renal disease

Question 24

Describe the metabolism of Arsenic Trioxide.

Answer 24

The metabolism of this drug is as follows:
- Systemic exposure to metabolites may also be increased in patients with renal impairment

Question 25

What are the notable ADRs of Tretinoin?

Answer 25

The notable ADRs of this drug are:
- Differentiation Syndrome (DS)
- Pregnancy risk/fetal deformity

Question 26

What are the notable ADRs of Arsenic Trioxide?

Answer 26

The notable ADRs of this drug are:
- Differentiation Syndrome (DS)
- QTc Prolongation

Question 27

What drug(s) is notable for causing Differentiation Syndrome (DS)?

Answer 27

The drugs in this class notable for cause this condition are:
- Tretinoin
- Arsenic Trioxide

Question 28

What APL drug(s) is notable for causing QTc Prolongation?

Answer 28

The drugs in this class notable for cause this condition are:
- Arsenic Trioxide

Question 29

What APL drug(s) is notable for causing fetal deformity?

Answer 29

The drugs in this class notable for cause this condition are:
- Tretinoin

Question 30

Describe the strategy and rationale for management of Differentiation Syndrome (DS).

Answer 30

The strategy and rationale for management of this condition caused by this drug are:
- While acute promyelocytic leukemia (APL) is highly treatable, this is a potentially fatal complication of APL treatment.
- It occurs in approximately 25% of patients who are treated for APL and typically presents in the first 7-12 days of treatment.
- The pathogenesis of DS is incompletely understood, but in APL, treatment can induce maturation of promyelocytes and promote tissue infiltration which is linked to the production of inflammatory cytokines.
- Patients are started on APL induction therapy in the hospital to closely monitor for DS.
- Typical clinical findings of DS include dyspnea, fever, peripheral edema, hypotension, weight gain, pleuro-pericardial effusion, acute renal failure, musculoskeletal pain, and hyperbilirubinemia
- Treatment of DS includes prompt steroid treatment and holding agents that can cause DS (ATRA and ATO) until signs and symptoms resolve. (Both ATRA and ATO have black boxed warnings for DS).
- These agents are typically restarted at a lower dose before slowly titrating back up to full dose.

Question 31

Describe the strategy and rationale for management of QTc Prolongation caused by Arsenic Trioxide.

Answer 31

The strategy and rationale for management of this condition caused by this drug are:
- This drug has a black box warning for QTc interval prolongation, complete atrioventricular block, and torsade de pointes, which can be fatal.
- Before administering this drug, assess the OTc interval, correct pre-existing electrolyte abnormalities (Potassium >4 and magnesium >2), and consider discontinuing drugs known to prolong OTc interval.
- EKGs should be checked at baseline and 1-2 times per week during therapy.
- QTc is calculated using the Framingham formula (QTc = QT interval + 154 * (1 - RR interval)) and QTc elevation is considered to be >450-500 msec.
- Withhold arsenic trioxide until resolution and resume at reduced dose for QTc prolongation.

Question 32

Describe the strategy and rationale for management of fetal deformity caused by Tretinoin.

Answer 32

The strategy and rationale for management of this condition caused by this drug are:
- There is a high risk that a severely deformed infant will result if this drug is administered during pregnancy.
- Within 1 week prior to starting tretinoin therapy, collect blood or urine from the patient for a serum or urine pregnancy test with a sensitivity of at least 50 milliunits/mL.
- When possible, delay therapy until a negative result from this test is obtained.

Question 33

Describe the history of Hydroxyurea.

Answer 33

The history of this drug is as follows:
- Hydroxyurea was the first drug FDA approved for the treatment of sickle cell disease back in 1998.
- It was nearly 20 years before another drug was approved for sickle cell disease in 2017!
- Since then, there have been 3 new drug approvals and more therapies are being investigated.

Question 34

What are the notable ADRs of Hydroxyurea?

Answer 34

The notable ADRs of this drug are:
- Myelosuppression
- Hair Thinning
- Skin/Nail Changes
- Birth Defects