Leukemia - Block 4 Flashcards
Describe the mechanism of AML and ALL?
- Cell expands and mutates
- Causes an imbalance between differentiation and proliferation
- Lekemic cells have growht/survival advantges to normal cells (crowding out)
- “Lymphocytic” means it develops from early (immature) forms oflymphocytes
- Immature cells are considered “Blasts”
What are the goals of acute leukemia tx?
Achieve a fast clinical and hematological remission
What are the presentations of acute lymphocytic leukemia?
- Tired, weak, malaise
- Bruising, pale skin
- DZ
- Infections
Classic B sx:
* Fever, night sweats, weight loss
Lab findings of ALL? Organ involvement?
Anemia - weakness, fatigue
Thrombocytopenia- GI bleeding, skin, gums, urine
Leukopenia - infection, fever
Spleen or liver enlargement
Bone pain
Mediastinal mass
Seizures/headaches
How do you diagnose ALL?
- Bone marrow aspirate and biopsy
- Lumbar puncture
- Marrow or blood > 19% blasts (normal <5%)
What are childhood ALL prognostic RF?
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
What is the tx schedule for ALL?
- Induction/remission (4wks)
- Cosolidation/intentification (4wk)
- Maintenance/Post consolidation (2-3yr)
What is considered cure?
5-10 yrs of complete remission
What is considered ALL complete remission?
- No evidence of leukemia in body
- Absence of leukemic blasts in peripheral blood
- <5% blasts in bone marrow
Complete remission DOES NOT mean cure
What is considered partial remission for ALL?
Significant response to tx, 5-25% blasts remaiun
What is considered relapse for ALL?
Recurrance of leukemic blasts
How long does it normally take children ALL to acheve complete remission?
day 28 of tx
How do we manage induction?
- TLS tx
- IV ABX
- Blood products
What is the goal of CNS prophylaxis?
Eradicat undetectatable leukemia in CNS and prevent leukemia from spreading to the CNS
What is the rationale of CNS prophylaxis?
<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
What are the drugs for CNS prophylaxis?
- Intrathecal cytarabine, hydrocortisone, methotrexate
- Cranial irradiation (long-term ADR)
- High dose IV methotrexate or cytarabine
What are the drugs used for consolidation/intensification?
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)
What is the goal of consolidation/intensification?
After CR achieved to further eradicate residual or undetectable dx and maintain remission
What is the goal for maintenance tx?
Further eradicate residual leukemic cells and prolong remission duration
Tx for relapse
Treatment is dependent on how long after chemotherapy they relapse
* Stem cell transplant is option
Tx for Ph+?
More aggressive add BCR-ABL inhibitor
Tx for Ph-? ADR?
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)
Presentaion fo AML?
Classic B sx
RF of AML?
- Increasing age
- Smoking
- Chemical exposure
- Previous chemo/radiation tx
- Male
Prognositc factors of AML?
Secondary leukemia (poorer prognosis)
Older age: duration of remission is less compared to younger patients
Tx schedule for AML?
- Remission induction
- Post induction/consolidation (2-4 months)
- DC therapy or bone marrow transplant
Indications for AML tx?
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)
What is the tx regimen for standard induction? ADR?
- 7 days of continuous infusion cytarabine
- 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
What is the goal of AML remission induction? Duration?
To rapidly induce a complete remission (CR)
Duration 1-2 yrs
Rationale of Post induction/Consolidation for AML?
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
What would you use in AML if poor prognostic factors and younger age?
Allogenic stem cell transplant
