Heme Malignancies

Question 1

AML origin

Answer 1

The leukemic blasts are from the myeloid lineage.

If 1 blast contains “Auer rod” = AML

Question 2

AML diagnosis

Answer 2

> 20% blasts c/w diagnosis of acute leukemia
Can present with leukocytosis or leukopenia
Typically functionally neutropenic at presentation
Often thrombocytopenia and anemia (fatigue, bleeding, pain)

Question 3

Good risk cytogenetics

Answer 3

t(8;21), t(15;17), inv(16)/t(16;16/del16q, FAB type M3

Question 4

Standard risk cytogenetics

Answer 4

Any one that is not good or poor LOL

Question 5

Poor risk cytogenetics

Answer 5

monosomy chromosome 5 or 7, del(5q), awn (3q26), t(6;9), complex karyotype or resistant disease after first course of chemo (> 5% of blasts in BM), no good risk features (induction followed by BMT), tp53, wild-type NPM1 and FLT3-ITD high

Question 6

induction therapy definition

Answer 6

goal is to reduce the total body leukemia cell population from 10^12 to below detectable level of 10^9

Question 7

Typical induction therapy for AML

Answer 7

7+3
7 consecutive days of cytarabine (100-200mg/m2/day) continuous infusion
3 consecutive days of Daunorubicin (45-90 mg/m2/day) IV push

Question 8

How many patient typically obtain CR after induction therapy?

Answer 8

60-80% depending on age and selection.

if patient is over 60 years then 50% with a 5 year survival <10%

Question 9

Following induction therapy, when is BM BX day

Answer 9

day 14-16

Question 10

What measurement are you looking at in BM BX for an AML patient

Answer 10

if <5% blasts, wait for full recovery = Plts > 100K and ANC >1500, which takes about 45 days prior to starting consolidation treatment

If >5% blasts give more chemotherapy: typically “5+2” (5 days cytarabine, 2 days daunorubicin). Day 29 repeat BM BX

Question 11

What are the goals of treatment for AML

Answer 11

1. Induction therapy: to reduce gross leukemia to undectable levels and to achieve CR
2. Reduce 10^9-10^10 cells, undetectable by standard means.
   If they don’t reduce cells down to 10^9-10^1- cells, pt requires more chemotherapy

Question 12

Consolidation therapy definition

Answer 12

treatment given after induction therapy if remission achieved

Question 13

Rec. consolidation therapy for AML patient

Answer 13

1. Cytarabine (1000-3000mg/m2/day) infusion Q12hrs QOD on D1-D5
   Doses usually X4 cycles with recovery between each cycle

Can use 5+2 treatment but typically only used in its >60years –> lower dose of cytarabine therefore lowering the risk of cerebellar toxicity

Question 14

Side effects of consolidation therapy for AML

Answer 14

Cytarabine
5-8% of patients have irreversible cerebellar ataxia (increased risk with >60 years, Creat >1.2, elevated Alk phos)

Requires cerebellar testing prior to every dose – finger to nose, heel to shin, signature comparison

High fevers to 105 (hold Abx and cultures unless symptomatic), HA, rashes with erythematous ears, extremities, and chest – can have hand/foot peelings

Requires Dexamethasone eye drops until 72h after last dose to prevent chemical conjunctivitis

Question 15

Tumor lysis syndrome

Answer 15

condition that occurs when a large number of cancer cells die within a short period, releasing their contents in to the blood

S/Sx: rapid development of hyperuricemia,hyperkalemia (weakness), hyperphosphatemia, hypocalcemia ( positive Chvostek and Trousseau signs, vomitting, cramps, seizures, AMS), and acute kidney injury.

Question 16

TLS labs

Answer 16

Typically occurs 1-3 days after induction of chemotherapy

BUN, creatinine, phosphate, uric acid, and calcium levels, actate dehydrogenase, potassium

Question 17

TLS prevention/treatment

Answer 17

TLS labs BID

IV fluids: 200-300 per day, 5% dextrose —> monitor urinary output, can use furosemide

Allopurinol: prevent the formation of uric acid

Question 18

AML Relapse

Answer 18

Patients stay through their nadirs and here for ~30days

Develop fever, neutropenia, rashes, mucositis, typhlitis (inflammation of the cecum [first part of large intestine]), and secondary infections

Question 19

Options for Tx of AML Relapse

Answer 19

Mitoxantrone, Etoposide +/- Cytarabine

HIDAC (High dose Cytarabine)

Cytarabine + Clofarabine

Question 20

Blast crisis definition

Answer 20

when 30% of the cells in the blood or bone marrow are blast cells.

Blast cells are less conforming therefore blood flow in microcirculation can be impeded with clump of blast cells

*oncological emergency leads to high mortality rate

Question 21

Blast crisis in AML

Answer 21

Anemia, infection, and bleeding

Hyperleukocytosis and leukostasis: WBC > 100,000 or > 50,000

Local hyperemia: impeded blood flow and high metabolic activity of dividing blast cells with cytokine release –> endothelial damage and hemorrhage. Often manifests in the CNS and pulmonary system

Anemia and PRBC transfusion: can worsen blast crisis as it increases viscosity –> hold or transfuse slowly

Thrombocytopenia and transfusions: liberal use of transfusion to decrease risk of hemorrhage. Plts can be falsely elevated from blast cells

Hyperkalemia: can be falsely elevated as K is released from blasts during testing, requires repeat sample on heparin in lab

Question 22

Treatment of blast crisis

Answer 22

Goal: lower WBC as rapidly as possible.

Can use chemotherapy with standard induction therapy or high dose hydroxyurea

leukopheresis for pmts unable to start treatment due to metabolic ban or ARF

All pts get allopurinol (can stop when WBC <1000), +/- low dose cranial irradiation, XRT to the chest

Question 23

Treatment of metabolic abnormalities in blast crisis

Answer 23

Hyperuricemia:

1. Allopurinol 300mg/day PO
2. IV hydration with NS, goal urine output 150cc/hr, can add lassix
3. urate oxidase only when uric acid > 9mg

Hypokalemia: MC in monocytic secondary to elevated lysosome levels

Question 24

Acute Promyelocytic leukemia M3: APML

Answer 24

defined by t(15;17) [translocation of chromosome 15, and 17)

This causes dysfunction of the retinoid acid receptor –> stops the promyelocytes from maturing

Promyelocytes tend to have high amounts of Auer rods —> increased risk for coagulation

*medical emergency due to DIC

Question 25

What % of AML patients have APML

Answer 25

10%

Question 26

APML can occur as secondary malignancy after what two chemo drugs

Answer 26

etoposide and doxorubicin

Question 27

What are favorable prognostic factors in APML

Answer 27

WBC <10,000/micoL and Plt > 40K

Question 28

S/Sx of APML

Answer 28

most present with bleeding –> DIC
Labs can show elevated PT, PTT, and decreased fibrinogen
Decreased Plts

Question 29

DIC management

Answer 29

coagulation parameters (D-dimer, fibrinogen, plts) monitored closely

Transfusion of platelets and cryoprecipitate or FFP are used to maintain Plt count above 20K-30K and plasma fibrinogen above 100-150 mg/dL

Question 30

Disseminated Intravascular Coagulation (DIC)

Answer 30

when the blood coagulates and forms many blood clots –> organ ischemia (kidneys, liver, lungs, and brain)

these blood clots are often formed from plts –> which lead to smallest injury to the blood vessel causing it to bleed

Lab findings: decreased plts, elevated PT, elevated PTT, elevated d-dimer

Question 31

APML treatment

Answer 31

all-trans retinoid acid (ATRA) + idarubicin

ATRA + arsenic (trisenox)
-preferred tx in >60 yrs

Question 32

ATRA side effects

Answer 32

HA, nasal stuffiness, red itchy/peeling skin, follicular rash

pseudotumor cerebri

transient elevated LFTs and hyperbillirubinemia

Question 33

ATRA syndrome

Answer 33

25% of patients have within 2-21 days

must talk to attending if suspect

fever, peripheral edema, pulmonary infiltrates, hypoxemia, respiratory distress, hypotension, renal and hepatic dysfunction, serositis –> pleural and pericardial effusions

can mimic sepsis

tx: dexamethasone (10mg IV Q 12 hrs for 3 or more days)

Question 34

If use arsenic in treatment of APML what do you need to monitor

Answer 34

Telemetry and EKG for QTc prolongation (reports of torsades)

telemetry for first three days of therapy then EKG baseline repeat twice weekly