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1

What is Leukemia?

A group of malignant diseases of the bone marrow and blood resulting from uncontrolled proliferation of myeloid or lymphoid cells

2

What is AML?

Acute Myelogenous Leukemia

3

What is CML?

Chronic Myelogenous Leukemia

4

What is ALL?

Acute Lymphocytic Leukemia

5

What is CLL?

Chronic Lymphocytic Leukemia

6

What is Acute Leukemia?

Impaired differentiation and proliferation of immature cells (blasts). Sudden onset and rapid progression. Survival: weeks to months without treatment

7

What is Chronic Leukemia?

Proliferation of relatively mature cells. Slow onset, often asymptomatic. Survival: years with supportive care

8

What is the average age at diagnosis for AML?

67

9

What is the pathogenesis of AML?

Leukemic blast cells: 1) have limited ability to differentiate normally, 2) crowd out other cells and inhibit normal hematopoiesis in bone marrow, 3) May affect one or more myeloid lineages, 4) "leak" into peripheral blood

10

What is the clinical presentation of AML?

Neutropenia (frequent infection, fever). Thrombocytopenia (easy bruising and bleeding). Anemia (fatigue, pale mucous membranes). Lab abnormalities (increased LDH, uric acid, serum creatinine, etc)

11

What is the treatment overview for AML?

AML progresses rapidly --> treatment should be initiated ASAP. Treat with CURATIVE intent for most patients. Choice of therapy depends on age, comorbidities, performance status, and cytogenetics. Chemotherapy

12

What are the treatment phases for AML?

Induction (achieve disease remission (normal blood count, no bone marrow disease)). Consolidation (eradicate residual disease and reduce risk of relapse). Maintenance (destroy any remaining leukemic cells to maintain disease-free state)

13

What is the standard therapy for AML Induction (< 60 yo)?

Combination of cytarabine and an anthracycline (1-2 cycles). "7+3": Cytarabine on days 1-7, and Idarubicin or Daunorubicin on days 1-3

14

What is an alternative to the "7+3" treatment for AML induction (< 60 yo)?

HiDAC = High Dose Ara-C (1 cycle). Cytarabine (high dose) and Ibarubicin or Daunorubicin on days 1-3

15

What is the treatment of AML Induction (> 60 yo) like?

High frequency of unfavorable cytogenetics, secondary AML, and comorbidities. Choice of treatment depends on performance status and cytogenetics: Standard induction (7+3), Low intensity chemotherapy (who can't handle 7+3). Intermediate intensity chemotherapy. Best supportive care

16

What are the ADRs with Idarubicin (Idamycin)?

Cumulative cardiotoxicity (>150mg/m2), as with most anthracyclines. Myelosuppression, alopecia, increased LFTs, urine discoloration. VESICANT

17

What is the emetogenicity like for Idarubicin?

Moderate

18

What are the ADRs with Cytarabine (Ara-C)?

Myelosuppression, fever, rash, tumor lysis syndrome

19

What is the Emetogenicity with Cytarabine (Ara-C)?

Low to moderate

20

What is the problem with HIGH DOSE Cytarabine (Ara-C)?

Myelosuppression. Cerebellar toxicity (watch for tremors,slurred speech, etc). Conjunctivitis

21

What is Clofarabine (Clolar) used for?

Relapsed pediatric ALL. In elderly patients with AML with poor prognostic factors

22

What are the ADRs with Clofarabine (Clolar)?

Myelosuppression! Capillary leak syndrome, hepatotoxicity

23

What is the Emetogenicity like for Clofarabine (Clolar)?

Moderate

24

What is Azacitidine (Vidaza)?

DNA Hypomethylator

25

What is Azacitidine (Vidaza) used for?

Myelodysplasic syndrome (MDS). In elderly patients with AML with low blast count (20-30%)

26

What are the ADRs with Azacitidine (Vidaza)?

Myelosuppression! N/V

27

What is the Emetogenicity like with Azacitidine (Vidaza)?

Moderate

28

What is Decitabine (Dacogen)?

Similar to Azacitidine. Approved for MDS and in elderly patients with AML

29

What are the ADRs with Decitabine (Dacogen)?

Myelosuppression, fatigue

30

What is the Emetogenicity with Decitabine (Dacogen)?

Minimal