Heme Malignancies Flashcards
AML origin
The leukemic blasts are from the myeloid lineage.
If 1 blast contains “Auer rod” = AML
AML diagnosis
> 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)
Good risk cytogenetics
t(8;21), t(15;17), inv(16)/t(16;16/del16q, FAB type M3
Standard risk cytogenetics
Any one that is not good or poor LOL
Poor risk cytogenetics
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
induction therapy definition
goal is to reduce the total body leukemia cell population from 10^12 to below detectable level of 10^9
Typical induction therapy for AML
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
How many patient typically obtain CR after induction therapy?
60-80% depending on age and selection.
if patient is over 60 years then 50% with a 5 year survival <10%
Following induction therapy, when is BM BX day
day 14-16
What measurement are you looking at in BM BX for an AML patient
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
What are the goals of treatment for AML
- Induction therapy: to reduce gross leukemia to undectable levels and to achieve CR
- 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
Consolidation therapy definition
treatment given after induction therapy if remission achieved
Rec. consolidation therapy for AML patient
- 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
Side effects of consolidation therapy for AML
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
Tumor lysis syndrome
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.
TLS labs
Typically occurs 1-3 days after induction of chemotherapy
BUN, creatinine, phosphate, uric acid, and calcium levels, actate dehydrogenase, potassium
TLS prevention/treatment
TLS labs BID
IV fluids: 200-300 per day, 5% dextrose —> monitor urinary output, can use furosemide
Allopurinol: prevent the formation of uric acid
AML Relapse
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
Options for Tx of AML Relapse
Mitoxantrone, Etoposide +/- Cytarabine
HIDAC (High dose Cytarabine)
Cytarabine + Clofarabine
Blast crisis definition
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
Blast crisis in AML
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
Treatment of blast crisis
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
Treatment of metabolic abnormalities in blast crisis
Hyperuricemia:
- Allopurinol 300mg/day PO
- IV hydration with NS, goal urine output 150cc/hr, can add lassix
- urate oxidase only when uric acid > 9mg
Hypokalemia: MC in monocytic secondary to elevated lysosome levels
Acute Promyelocytic leukemia M3: APML
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
What % of AML patients have APML
10%
APML can occur as secondary malignancy after what two chemo drugs
etoposide and doxorubicin
What are favorable prognostic factors in APML
WBC <10,000/micoL and Plt > 40K
S/Sx of APML
most present with bleeding –> DIC
Labs can show elevated PT, PTT, and decreased fibrinogen
Decreased Plts
DIC management
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
Disseminated Intravascular Coagulation (DIC)
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
APML treatment
all-trans retinoid acid (ATRA) + idarubicin
ATRA + arsenic (trisenox)
-preferred tx in >60 yrs
ATRA side effects
HA, nasal stuffiness, red itchy/peeling skin, follicular rash
pseudotumor cerebri
transient elevated LFTs and hyperbillirubinemia
ATRA syndrome
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)
If use arsenic in treatment of APML what do you need to monitor
Telemetry and EKG for QTc prolongation (reports of torsades)
telemetry for first three days of therapy then EKG baseline repeat twice weekly
