Acute Leukemias

Question 1

how does one develop AML?

acute myeloid leukemia

Answer 1

can have tranformation from myelodysplastic syndrome, myeloproliferative (PV or CML or primary myelofibrosis).

AML can also develop after benzene exposure

Question 2

Acute Myeloid Leukemia or AML has this on peripheral smear:

and other facts

Answer 2

See Auer rods with APL subtype.

>20% of myeloblasts on peripheral smear or bone marrow

see easy bruising, fatigue, infectious with pancytopenia on labs

poor prognosis in older ppl >60 yrs and younger pts can be treated with chemo and then stem cell transplant

Question 3

treatment of AML subtype M3

Answer 3

If auer rod seen in APL subtype with M3, give all trans-retinoic acid even before t(15.17) testing is completed.

induction chemo to restore normal bone marrow function.

Question 4

chemotherapy for AML (acute myeloid leukemia)

Answer 4

7+3

7 day continuous IV infusion of cytarabine + short infusion of anthracycline or doxorubicin on days 1-3

need to get an TTE prior to treatment

Question 5

side effect of anthracyclines?

Answer 5

cardiotoxicity and so needs baseline TTE prior to treatment.

Question 6

what is seen on acute myeloid leukemia bone marrow biopsies?

Answer 6

AML is a umbrella term and encompasses both APL and Acute promyelocytic leukemia with subtype M3 Diagnosis is >20% blasts.

Question 7

what is seen in acute promyelocytic leukemia (APML) on bone marrow biopsy

Answer 7

see low blast cell count but would see hypergranular promyelocytes

Question 8

when do we use all trans retinoic acid + anthracycline based chemotherapy?

Answer 8

for acute promyelocytic leukemia (APML)

sub type

has chromosomal translocation of t(15,17)

Question 9

AML presentation

Answer 9

fatigue, fever, loss of appetite and weight and night sweats.

leukemia cells divide at a faster rate than normal cells

anemia - causes a lot of the symptoms

loss of normal WBC - results in recurring infections and fevers.

Question 10

what is acute leukemia?

Answer 10

hematological malignancy characterized by infiltration of the tissues- bone marrow, blood, and other tissues- by uncontrolled proliferation and abnormal delayed differentiation of clonal myeloid or lymphoid precursor cells

this makes up >20% of bone marrow

includes AML and ALL in adults.

Question 11

presentation of AML (acute myeloid leukemia)?

Answer 11

petechiae, epistaxis and mucosal hemorrhages when plts<20K

anemia, thrombocytopenia and functional neutropenia despite having elevated WBC

Question 12

cure rates in AML <60 yrs is

Answer 12

60-85%

Question 13

APL subtype with M3 treatment is with

Answer 13

all trans-retinoic acid

Question 14

AML treatment is with

Answer 14

induction therapy with anthracycline like daunorubicin and infusional cytarabine.

goal: ablate the bone marrow and eliminate the blasts - destroys normal hematopoietic cells as well.

cells are expected to recover after a period of aplasia (3-4 weeks) and supported with transfusions or abx if fevers

consolidation therapy for responders consists of additional cycles of chemotherapy in low risk and allogenic hematopoeitic stem cell transplant in high risk pts.

Question 15

AML tx for older frail pts is with:

Answer 15

symptomatic management - blood and platelet tranfusions

single agent chemotherapy - hydroxyurea, and low dose cytarabine and hypomethylating agents- decitabine and azacitidine.

only expect to survive months; needs hospice care.

Question 16

ALL (acute lymphoblastic leukemia) is seen in what demographics?

Answer 16

more in children; pediatric ALL is more likely cured

adult (>19 years) ALL is worse.

Question 17

acute lymphoblastic leukemia presentation:

Answer 17

malaise

bleeding

infections

bone pain

rarely CNS changes

Question 18

ALL (acute lymphoblastic leukemia) is

Answer 18

75% B cell lineage - extramedullary, GI, and testicular involvement.

25% T cell lineage- mediastinal mass and SOB, stridor or wheezing. See skin involvement

diagnosis is with immunophenotype, cytogenetics and molecular abnormalities.

Philiadelphia chromosome - use imatinib or dasatinib for treatment

Question 19

Treatment of ALL (acute lymphoblastic leukemia) is with:

Answer 19

Philiadelphia chromosome POSITIVE ALL - imatinib and dasatinib followed by traditional chemotherapy for superior remission

remission induction they should get autologous or allogenic hematopoeitic stem cell transplant

Treatment regimens are:

induction therapy: vincristine, anthracycline, corticosteroids, and L asparginase. some have allergic reactions, hypofibrinogenemia, hypertriglyceridemia .

CNS prophylaxis is needed in ALL

maintenance therapy/phase: oral mercaptopurine daily and methotrexate weekly for 2 years.

Question 20

Survivors of childhood leukemia are at risk for:

what to screen for?

Answer 20

secondary cancer

CAD

metabolic syndrome - high BMI, truncal obesity, dyslipidemia, insulin resistance, HTN

Need to get screening lipid profile, DM2 and HTN

TTE surveillance for LV dysfunction at 3-5 years if anthrocycline exposure was high (>300 of doxorubicin) or if chest radiation was used

female survivors are high risk for myocardial dysfunction in pregnancy

osteopenia - b/c of high dose steroids

Question 21

cranial radiation increases risk for:

Answer 21

stroke and neurocognitive deficits

Question 22

screen patients with childhood leukemia (ALL) for:

Answer 22

Need to get screening lipid profile, DM2 and HTN

TTE surveillance for LV dysfunction at 3-5 years if anthrocycline exposure was high (>300 of doxorubicin) or if chest radiation was used

female survivors are high risk for myocardial dysfunction in pregnancy

DEXA - for osteopenia

Question 23

what other tumors are ALL pts more likely to develop as adults?

Answer 23

skin cancer,

thyroid and parotid cancer

sarcomas

brain tumors.

secondary cancer risk is highest at 30 years (11%)

Question 24

APML t (15,17) treatment with auer rods

Answer 24

good prognosis.

Question 25

APML t(9,22) prognosis

Answer 25

bad prognosis

treatment <50 yrs: ara-C (cytarabine) and daunorubicin -> then to allogenic bone marrow transplant

>50 yrs: ara-C (cytarabine) and daunorubicin

M3 is treated with all trans-retinoic acid

Question 26

what skin condition is associated with AML?

Answer 26

sweet’s syndrome

see tender erythematous plaques and nodules on face and extremities. if biopsied shows dense neutrophilic infiltrates.

If seen, get a bone marrow biopsy to look for AML.

Question 27

what is this rash seen with AML?

Answer 27

Sweet’s syndrome.