Leukemia - Block 4

Question 1

Describe the mechanism of AML and ALL?

Answer 1

1. Cell expands and mutates
2. Causes an imbalance between differentiation and proliferation
3. Lekemic cells have growht/survival advantges to normal cells (crowding out)
4. “Lymphocytic” means it develops from early (immature) forms oflymphocytes
5. Immature cells are considered “Blasts”

Question 2

What are the goals of acute leukemia tx?

Answer 2

Achieve a fast clinical and hematological remission

Question 3

What are the presentations of acute lymphocytic leukemia?

Answer 3

1. Tired, weak, malaise
2. Bruising, pale skin
3. DZ
4. Infections

Classic B sx:
* Fever, night sweats, weight loss

Question 4

Lab findings of ALL? Organ involvement?

Answer 4

Anemia - weakness, fatigue
Thrombocytopenia- GI bleeding, skin, gums, urine
Leukopenia - infection, fever

Spleen or liver enlargement
Bone pain
Mediastinal mass
Seizures/headaches

Question 5

How do you diagnose ALL?

Answer 5

1. Bone marrow aspirate and biopsy
2. Lumbar puncture
3. Marrow or blood > 19% blasts (normal <5%)

Question 6

What are childhood ALL prognostic RF?

Answer 6

Standard risk:
* 1-10 YO
* WBC <50
* Karyotype: No t(9;22) or (4;11)

High risk:
* <1 and ≥10 YO
* WBC ≥50
* t(9;22) or (4;11)
* Dx in CNS or testes
* Male
* Response to induction therapy >4wks
* Down’s syndrome

Question 7

What is the tx schedule for ALL?

Answer 7

1. Induction/remission (4wks)
2. Cosolidation/intentification (4wk)
3. Maintenance/Post consolidation (2-3yr)

Question 8

What is considered cure?

Answer 8

5-10 yrs of complete remission

Question 9

What is considered ALL complete remission?

Answer 9

1. No evidence of leukemia in body
2. Absence of leukemic blasts in peripheral blood
3. <5% blasts in bone marrow

Complete remission DOES NOT mean cure

Question 10

What is considered partial remission for ALL?

Answer 10

Significant response to tx, 5-25% blasts remaiun

Question 11

What is considered relapse for ALL?

Answer 11

Recurrance of leukemic blasts

Question 12

How long does it normally take children ALL to acheve complete remission?

Answer 12

day 28 of tx

Question 13

How do we manage induction?

Answer 13

1. TLS tx
2. IV ABX
3. Blood products

Question 14

What is the goal of CNS prophylaxis?

Answer 14

Eradicat undetectatable leukemia in CNS and prevent leukemia from spreading to the CNS

Question 15

What is the rationale of CNS prophylaxis?

Answer 15

<5% present with blasts in CNS
Sanctuary sites: CNS and testes
* Drugs don’t easily penetrate BBB
* Pt with no CNS involvement at diagnosis relapse in CNS/testes (50-85%)

CNS prophylaxis decreased relapses to <2% in children

Question 16

What are the drugs for CNS prophylaxis?

Answer 16

1. Intrathecal cytarabine, hydrocortisone, methotrexate
2. Cranial irradiation (long-term ADR)
3. High dose IV methotrexate or cytarabine

Question 17

What are the drugs used for consolidation/intensification?

Answer 17

Vincristine, mercaptopurine and IT methotrexate

May add cyclophosphamide, cytarabine or peg-asparaginase to high risk

May do allogeneic stem cell transplant for patients with high risk factors (needing a donor match)

Question 18

What is the goal of consolidation/intensification?

Answer 18

After CR achieved to further eradicate residual or undetectable dx and maintain remission

Question 19

What is the goal for maintenance tx?

Answer 19

Further eradicate residual leukemic cells and prolong remission duration

Question 20

Tx for relapse

Answer 20

Treatment is dependent on how long after chemotherapy they relapse
* Stem cell transplant is option

Question 21

Tx for Ph+?

Answer 21

More aggressive add BCR-ABL inhibitor

Question 22

Tx for Ph-? ADR?

Answer 22

Blinatumomab (Blincyto®)
Bispecific CD 19-directed CD3 T-cell Engager

ADR: Cytokine release syndrome (fever, HA, diarrhea, rash, myalagias)
* Nerological tox (confusion, loss of consciousness, behavior changes, sz, cerebral edema, elevated intracranial pressure)

Question 23

Presentaion fo AML?

Answer 23

Classic B sx

Question 24

RF of AML?

Answer 24

1. Increasing age
2. Smoking
3. Chemical exposure
4. Previous chemo/radiation tx
5. Male

Question 25

Prognositc factors of AML?

Answer 25

Secondary leukemia (poorer prognosis)

Older age: duration of remission is less compared to younger patients

Question 26

Tx schedule for AML?

Answer 26

1. Remission induction
2. Post induction/consolidation (2-4 months)
3. DC therapy or bone marrow transplant

Question 27

Indications for AML tx?

Answer 27

Performance Status (PS) of Patient: elderly not CI but PS may predict tolerance

Immediate tx required:
* Hospital stay
* Intensive high dose therapy (Infection, neutropenia, bleeding)

Question 28

What is the tx regimen for standard induction? ADR?

Answer 28

1. 7 days of continuous infusion cytarabine
2. 3 days of idarubicin or daunorubicin

CR within 1-2 cycles
7+3 controversial in pt under 60-maybe higher doses should be used

ADR: prolonged neutropenia

Question 29

What is the goal of AML remission induction? Duration?

Answer 29

To rapidly induce a complete remission (CR)

Duration 1-2 yrs

Question 30

Rationale of Post induction/Consolidation for AML?

Answer 30

Most patients will relapse within 4-8 months without further treatment

Goal: Additional therapy is warranted to eradicate residual leukemic cells and to prevent drug-resistant disease

Question 31

What would you use in AML if poor prognostic factors and younger age?

Answer 31

Allogenic stem cell transplant