3.28.14* Drug Treatment of Hematologic Malignancies

Question 1

Difference between therapy for solid tumors and hematologic malignancies.

Answer 1

solid tumor treatments have dose-limiting toxicity as myelosuppression. For leukemias, lymphomas and multiple myelomas, the treatment is myelosupression, thus patients are severely immunocompromised and at increased risk of opportunistic infections.

Question 2

stages of chemo treatment

Answer 2

induction
consolidation
maintenance

Question 3

ALL (acute lymphoblastic leukemia) is seen mainly in

Answer 3

kids

Question 4

CLL (chronic lymphocytic leukemia) is seen mainly in

Answer 4

old

Question 5

Drugs for AML

Answer 5

cytarabine (ara-c)
daunorubicin
thioguanine

Post-remission: cytarabine

Question 6

cytarabine (ara-c)

Answer 6

AML

pyrimidine analog

Question 7

daunorubicin

Answer 7

AML

free radical generator, intercalator and topo II inhibitor

Question 8

thioguanine

Answer 8

AML

purine analog

Question 9

Acute Promyelocytic Leukemia (acute PML) treatment

Answer 9

(acute PML is caused by constituitively active PML/RARalpha fusion gene)

b. intial treatment all-trans-retinoic acid (ATRA) combined with daunorubicin or idarubicin plus cytarabine
b. alternatively arsenic trioxide is used in patient who cannot tolerate anthracycline

Question 10

ATRA (retinoid drug,Tretinoin ) MOA in acute PML

Answer 10

disrupts fusion of genes and restores differentiation process.

Question 11

fusion gene that causes acute promyelocytic leukemia?

Answer 11

PML/RARalpha: results in dedifferentiated proliferaton of promyelocytes

Question 12

retinoic acid syndrome

Answer 12

fever, dyspnea, weight gain, pulmonary infiltrates, pleural or pericardial effusions

Question 13

Arsenic trioxide MOA

Answer 13

(to treat acute PML)

also degrates PML-RAR-alpha fusion protein

Question 14

adverse effect of artsenic trioxide in the treatment of acute PML

Answer 14

Cardiovascular

AB block, QT prologation, electrolyte imbalance (all these are not seen in ATRA

Question 15

Drugs approved to treat Acute Lymphocytic Leukemia

Answer 15

Imatinib (TKI for BCR-Abl)
Pegasparagase
Prednisone
Vincristine
Daunorubicin/Doxorubicin
MTX
radiation

Question 16

Most common treatment for ALL

Answer 16

induction: imatinib and combination chemotherapy
consolidation: MTX + Mercaptopurine (two different antimetabolites)

Question 17

Pegasparagase MOA

Answer 17

a. degrades asparagine and thus blocks protein synthesis. Pegylated.
b. resistance can be due to upregulatin of asparagine synthetase

Question 18

What is the significance of pegylation?

Answer 18

extends the duration of a drug

Question 19

What are the adverse effects of pegasparagase?

Answer 19

pancreatitis (necrotic/inflammatory)
immune suppression hyperglycemia (due to no insulin)
clotting abnormalities
hypoalbumineumi

Question 20

Drugs approved for chronic myeloid leukemia

Answer 20

imatinib
dasatinib/nilotinib (second gen, good for alterations in ATP binding site)

(older: cytarabine + interferon)

Question 21

MOA of imatinib

Answer 21

TKI that binds to ATP binding site of BCR-ABL fusion gene

Question 22

what is the only curative treatment for CML >10 years?

Answer 22

allogenic bone marrow or stem cell transplant

Question 23

Drugs approved for CLL (chronic lymphocytic leukemia)

Answer 23

a. Flydarabine (antimetabolite) +
Cyclophosphamide (alkylating)
b. Fludarabine + Rituximab
c. All three
d. Bendamustine (antimetabolite and alkylating agent)

Question 24

CLL treatment complications

Answer 24

a. oppurtunistic infection
b. AHA and/or thrombocytopenia
c. Hyperuricemia by tumor lysis syndrome (need prophylaxis with allopurinol)

Question 25

Drugs for Hairy Cell Leukemia

Answer 25

Cladribine/Pentostatin (purine analogs)

Interferon

Question 26

interferon

Answer 26

direct tumor effect
a. prolongs all phases of cell cycle
b. induce cellular differentiation
induce host responses
a. activates NK, CD8 and macrophages
upregulates antigen presentation to T cells (tumor antigens)
b. keeps cells from being infected by virus

Question 27

Hodgkin lymphoma chemotherapy

Answer 27

most include:
Anthracyclin (doxorubacin)
Bleomycin (or cyclophasphamide; alkylating) 
Vincristine (mitotic spindle inhibitor)
Dacarbazine

Regimen is administered in cycles to prevent extremely low blood cell counts. Very good prognosis.

Acute side effects- hair loss, nausea/vomiting/diarrhea/malabsorption, ulceration, increased susceptibility to infections.

Long term side effects- secondary malignancy

Question 28

Treatment for NHL

Answer 28

high stage: ritixumab and CHOP

Question 29

what are the two radiolabeled CD20 mABs

Answer 29

Tostiumomab

Ibritumomab

Question 30

Burkitt Lymphoma

Answer 30

often EBV-associated
very aggressive
Cyclical drug cycle

Question 31

Drugs for Burkitt lymphoma

Answer 31

cyclophosphamide + MTX

vincristine + doxorubicin

Question 32

Antracyclines (doxorubucin, daunorubicin) have culmulative toxicity?

Answer 32

cardiopathic; Can cause cardiomyopathy and lead them to die of heart . Interaction with drugs and iron causing free radical damage. Chelating agents may help reduce cardiotoxicity.

Question 33

Chemotherapy consisted of 8 alternating courses every 21 days or earlier, but at least 14 days apart. What kind of approach is this?

Answer 33

hyperfractionated (to keep the doses low)

• good for toxicity
• good for resistance
• good for fast growing