Chemotherapy Of Leukemias

Question 1

Goal of therapy for ALL

Answer 1

Complete clinical and Hematological remission

Complete response (CR) is considered normal Cellularity with <5% of blasts 
- “cured” after 5 years of CR

Question 2

Percentage of ALL that goes into clinical remission

Answer 2

Childhood= 96-99%

Adult- 30-40%

More difficult to treat in adults

Question 3

Treatment phases of ALL

Answer 3

Induction: rapidly induce remission

CNS prophylaxis: CNS relapse

Consolidation therapy: eradicate clinically undetectable disease

Delayed intensification: maintain remission

Interim maintenance: maintain remission

Maintenance therapy: maintain remission

Question 4

1st line for ALL induction

Answer 4

Vincristine + Glucocorticoids + anthracycline
- may or may not include pegaspargase

• if Ph+ (Philadelphia chromsome), add imatinib*

Question 5

What organism does anthracyclines develop from?

Answer 5

Streptomycin peucetius
- develops red urine/ fluids in hosts

MOA:

• intercalated into DNA
• Inhibition of topoisomerase 2
• Generation of semiquinone free radical and oxygen free

Major ADRs = alopecia and cardiotoxicity, mucositis

Question 6

Why is anthracyclines cardiotoxic specifically?

Answer 6

Cardiac tissue lacks catalase and can only reduce hydrogen peroxide into free radical form

Life time dose = 550 mg/m2

Question 7

Mitoxantrone

Answer 7

Synthetic agent of daurubicin and doxorubicin that causes green/blue urine and fingernails

MOA =. Similar to anthracyclines except DOES NOT generate free radicals

• no cardiotoxicity, but still presents with alopecia and mucositis

Question 8

Imatinib

Answer 8

Tyrosine kinase antibody that is added to chemotherapy regiments if Philadelphia chromosome is present t(9;22)

Question 9

Acute lymphoid leukemia CNS prophylaxis

Answer 9

Treat via intrathecal methotrexate and cranial irradiation (specifically in sanctuary sites).
- this is because cancer cells like to hid in sanctuary areas

Question 10

Methotrexate MOA

Answer 10

Methotrexate gets polyglutamated and forms (MTX-PG) complex

This complex directly inhibits DHFR and indirectly inhibits thymidylate synthase

Specific ADRs = mucositis, phototoxicity and nephrotoxicity

Question 11

How does leucovorin “rescue” methotrexate toxicity?

Answer 11

It generates the cofactors needed for synthesis of pyrimidine and purine nucleotides in healthy cells
- essentially antagonizes methotrexate

Question 12

G-mercaptopurine and 6-Thioguanine

Answer 12

Both inhibt biosynthesis of AMP and GMP

Specifically, Thioguanine blocks IMP dehydrogenase and mercaptopurine blocks Inosine monophosphate (IMP) itself

Question 13

What is acrolein?

Answer 13

Urotoxic metabolite that is built up via cyclophosphamide and ifosfamide (Cytoxane)

Combat via hydration and Mensa when taking these drugs

Question 14

ALL maintance therapy

Answer 14

Goal is to stay in remediation

Uses POMP regiment

Question 15

AML induction therapy

Answer 15

Goal is to induce remission w/ roughly 50% achieving this goal

Standard of care = 7 + 3

• 7 days of cytarabine
• 3 cays of anthracycline

Question 16

CML goal of therapy

Answer 16

Eradicate clones and maintance the chronic phase

Can only be cured by allogeneic hematopoietic stem cell transplants