Acute Leukemia

Question 1

Initial Presentation

Answer 1

• Pancytopenia => pallor, fatigue, anorexia, bleeding, infection
• Febrile neutropenia
• Pancytopenia requires transfusions and won’t stop until remission occurs
• Hyperuricemia, before or soon after first treatment

Question 2

Hyperuricemia Treatment

Answer 2

• Allopurinol 300 mg with IV hydration including sodium bicarbonate
• Start a few days before first chemo to prevent tumor lysis syndrome
• Use rasburicase in those with significant uric acid elevations, renal dysfunction, or high WBC

Question 3

Acute Lymphoblastic Leukemia Treatment

Answer 3

• Combination chemo

- 3 phases: remission induction, consolidation, and maintenance phases

Question 4

Induction Phase

Answer 4

• Given regardless of ANC and platelet counts
• Prednisone or Dexamethasone, vincristine, L-asparaginase, +/- daunorubicin
• Duration ~4 weeks
• 2nd inductions used
• Adults and high risk children often have 2nd induction

Question 5

CNS Preventative Therapy

Answer 5

• Present in most patients and undetectable
• Caused relapse in CNS and then bone marrow
• IT chemo is used with methotrexate +/- cytarabine and hydrocortisone (PF saline)
• Begins in induction phase and continues through each phase
• Methotrexate dosing varies by age

Question 6

Induction Agent AE

Answer 6

• Vincristine: neurotoxicity (fatal IT), give with laxatives
• Prednisone/Dexamethasone: behavioral changes, increased appetite
• Asparaginase: allergic rxn, rare clotting/bleeding or pancreatitis
• Daunorubicin/Doxorubicin: N/V, myelosuppression, cardiotox, vesicant injury
• Methotrexate: N/V

Question 7

Consolidation Phase

Answer 7

• Intensification/Re-intensification
• Decreases risk of developing resistance
• ~25 weeks generally
• CSF agents not usually employed during ALL treatment
• Antiemetic support is often needed
• Higher dose methotrexate is sometimes employed but the regimen is generally based on specific types of ALL

Question 8

Possible Consolidation Regimen Options

Answer 8

• Cyclophosphamide
• Cytarabine
• Mercaptopurine
• Methotrexate
• Vincristine
• PEG asparaginase
• Doxorubicin
• Dexamethasone

Question 9

Maintenance

Answer 9

• AKA Continuation Therapy
• ~100 weeks, excluding mature B-cell ALL
• Most would relapse without this therapy
• Methotrexate + mercaptopurine + VP pulses
• Vincristine + Prednisone (sometimes dexa instead) shown to improve outcome in all patients
• IT chemo approx every 12-16 weeks
• AE: low level myelosuppression, hepatic enzyme elevations

Question 10

Dose Adjusting Maintenance Therapy

Answer 10

• Based on WBC monitoring QW or QoW
• Maintain ANC in target range on 500-1500
• Adjust dosing based on a 6 week period
• Alternating dose increases of methotrexate or mercaptopurine by ~25% with at least 6-8 weeks between increases
• Impact of steroids on ANC elevation needs to be considered when deciding on methotrexate/mercaptopurine increases

Question 11

Treatment of Relapse

Answer 11

• Bone marrow relapse is most common
• Relapses during maintenance have worse prognosis for maintaining remission
• 4-drug induction regimen recommended: vincristine, prednisone, asparaginase, and daunorubicin
• Need another CNS prevention course and 2-3 years of more intensive consolidation/maintenance phases
• Some may be able to get bone marrow transplant

Question 12

Testicular Relapse?

Answer 12

• Testicular radiation therapy with 2400cGy +

- Chemotherapy listed for normal relapse patients

Question 13

Pharmacological Issues with ALL

Answer 13

• IDMTX: better remission rates but worse neurotoxicity
• Imatinib can be used for CML and BCR/AML+ ALL
• Late effects in life: cardiotox, skeletal morbidity (esp with dexamethasone), neurotoxicity

Question 14

AML

Answer 14

• Acute Myeogenous Leukemia
• Chemo approach depends on age, performance status, and genetics
• Standard chemo components: daunorubicin OR idarubicin + cytarabine
• Courses repeated 2-4 times based on risk status, response, and tolerance
• Severe myelosuppression, N/V, and mucositis
• CNS treatment with systemic chemo
• Post-remission therapy done after initial chemo and can include same agents with different dosing/schedules/etc
• Genetics is big determiner in resistance

Question 15

APML

Answer 15

• Acute Promyelocytic Leukemia
• Subtype of AML, 10% of AML
• Binding of retinoids leads to cell differentiations
• Has its own induction and consolidation phase

Question 16

APML Induction

Answer 16

Tretinoin
+
Arsenic Trioxide until remission

• Electrolyte abnormalities are common and need to check ECG
• ATRA + anthracycline is an alternative to arsenic

Question 17

APML Consolidation

Answer 17

Arsenic
+
ATRA

• Risk retinoic acid syndrome with initial course of ATRA (leukocytosis, fever, pulmonary infiltrates)
• Concomitant chemo, chemo at first sign of leukocytosis or dexamethasone to deal with syndrome

Question 18

Supportive Care for AML

Answer 18

• Some will give an antifungal +/- antibiotic during chemo
• Anti-emetics are employed throughout
• Routine CSF use not recommended