Leukemia

Question 1

Epidemiology

Answer 1

13780 new AML cases, 10200 deaths, inc exponentially after 50 y/o

Question 2

WHO definition

Answer 2

20% myeloid blasts in peripheral blood of BM; except if t(15;17), t(8;21), inv(16), t(16;16)

Question 3

FAB classification

Answer 3

M0-M7; M3=APML

Question 4

WHO classification

Answer 4

I. AML with recurrent genetic abnormalities
II. AML with MDS related changes
III. Therapy-related neoplasm
IV. AML not otherwise specified

Question 5

AML - Better Risk 5 yr OS 55-65%

Answer 5

Inv(16), t(16;16), t(8;21), t(15;17) –MM: normal cytogenetic with NPM1 mutation or isolated CEBPA mutation in absence of FLT3-ITD

Question 6

AML - Intermediate Risk 5 yr OS 24-40%

Answer 6

Normal cytogenetics, +8 only, t(9;11) –MM: t(8;21), Inv (16), f(16;16) with c-KIT mutation

Question 7

AML - Poor Risk 5 yr OS 5-14%

Answer 7

Complex (>3 abnormalities), -5, -7, 5q-, 7q-, abnormalities of 11q23 excluding t(9;11), inv(3), t(3;3), t(6;9), t(9;22); –MM: normal cytogenetics with FLT3-ITD mutation

Question 8

signs and symptoms

Answer 8

bone marrow failure(anemia-fatigue, weakness, CV effects; thrombocyto- bleeding; neutropenia- infx), extramedullary tissue invasion, leukostasis secondary to high WBC, TLS, chloroma (skin)

Question 9

When to use daunorubicin 90mg/m2 vs 45 in 7+3; NEJM 2009 study

Answer 9

good or intermediate risk OR less than 50y/o. improves CR 57.3->70.6, OS 15.7->23.7mo

Question 10

CR criteria

Answer 10

ANC>1000, Plt >100k, independent of tranfusions, BM Bx <5% blasts, absence of blasts with Auer rods, absence of extramedullary disease; disappearence of karyotype NOT required

Question 11

Treatment related problems

Answer 11

bone marrow suppression, TLS, N/V, organ toxicities, Mucositis/ stomatitis, Nutrition

Question 12

Mgmt of thrombocytopenia

Answer 12

menses suppression, stress ulcer px, acute bleeding treatment

Question 13

Induction tx evaluation Day 14-17 BMBx; significant residual blasts OR significant cytoreduction with residual blasts

Answer 13

re-induction 7+3

Question 14

Induction tx evaluation Day 14-17 BMBx; BM is hypoplastic

Answer 14

delay re-induction until status of marrow is clear

Question 15

why dose reduce araC from 3 to 1.5gm/m2 in those >60yo?

Answer 15

neurotoxicity

Question 16

post remission tx -favorable (better and intermediate) risk, better tolerated if <60yo

Answer 16

HD araC

Question 17

post remission tx -poor risk

Answer 17

allogeneic HSCT

Question 18

relapse tx

Answer 18

clinical trial prefered, if late relapse (>12mo) consider re-induction, if not salvage chemo then alloHSCT, best supportive care if not tx candidate

Question 19

> 60 yo

Answer 19

best course not known - can do best supportive care (hydrea, transfusions), std 7+3, or reduced intensity chemo (aza, decit)

Question 20

APML

Answer 20

t(15;17) fuses PML gene on chromosome 15 to RAR alpha on chromosome 17; PML-RAR fusion protein interferes with factors req’d for differentiation of myeloid precursors; follow by PCR, confirm “molecular remission”

Question 21

APML risks and CR

Answer 21

acheived in 90% of pts, without bone marrow aplasia, obtained at 25-70 days, high risk WBC >10k, coagulopathies major cause of early death (resolve within days of tx)

Question 22

ATRA toxicities

Answer 22

differentiation sx, HA, mucosal dryness, hyperleukocytosis

Question 23

APML and coagulopathies

Answer 23

plt >30k, fibrinogen >100 (cryo, FFP), hyperleukocytosis (start chemo other than ATRA)

Question 24

APML induction

Answer 24

ATRA + ida or dauno

Question 25

APML consolidation

Answer 25

ida or dauno x 2 cycle + ATRA (if high risk WBC >10k add araC)

Question 26

APML maintenance

Answer 26

ATRA + weekly MTX +/- 6-MP x 1-2 years

Question 27

arsenic trioxide

Answer 27

excellent outcomes in refractory pts, may play a role in consolidation, may use in induction for those that can not tolerate anthracycline

Question 28

arsenic trioxide toxicity

Answer 28

QTc, Mg++, K+

Question 29

ATRA differentiation sx

Answer 29

respiratory distress, fever, pulm infiltrates, weight gain, renal failure, hypotension

Question 30

ATRA differentiation sx management

Answer 30

dex IV 10mg q12h x3d (minimum), continue ATRA unless severe, then hold until resolves then restart ATRA

Question 31

ALL signs and symptoms

Answer 31

constitutional sx (fever, night sweats, wt loss), easy bruising/bleeding, dyspnea, bone pain, dizziness, infx, CNS involvement (mature B-cell ALL), mediastinal involvement (T-cell)

Question 32

ALL classification

Answer 32

>20% blasts in BMBs; B-cell more common in adult ALL (25% T-cell); most common cytogenetic t(9;22) (20-30%)->poor prognostic; t(4;11), hypodyploidy->also poor prognostic

Question 33

ALL unfavorable prognostic factors

Answer 33

Age >55yo, WBC >30k (>100k in T-cell), t(9;22), delayed time to induction of CR, CNS involvement, minimal resdidual dz after induction

Question 34

ALL induction - std

Answer 34

vincristine + anthracycline + corticosteroids; if poor prognostic ADD asparaginase, cyclophos, araC, and MTX; CNS px

Question 35

ALL induction - hyperCVAD + maintenance

Answer 35

hyperCVAD x8 cycles; CNS px; maintenance (risk stratified): 6MP, vincrisitine, MTX, pred

Question 36

TLS - high risk - hydration + rasburicase

Answer 36

Burkitt's, B-ALL, ALL with WBC >100k, AML >50k or monoblastic

Question 37

TLS - intermediate risk - hydration + allopurinol, consider rasburicase in peds

Answer 37

DLBCL, ALL with WBC 50-100k, AML with WBC 10-50k, CLL with WBC 10-100k or tx with fludarabine, others that are likely to have rapid response to tx (MM, CML, solid tumor)

Question 38

rasburicase - peds dosing

Answer 38

0.15-0.2 mg/kg IV daily (up to 7 days); pros: works in 2-4hrs; cons: cost, hypersensitivity

Question 39

ALL - Ph+

Answer 39

imatinib + hyperCVAD CR >90% (before TKIs was <20%) - can also use dasatinib 1st line; alloSCT only chance of cure, but use is debated

Question 40

refractory ALL - Ph+

Answer 40

ponatinib

Question 41

relapsed / refractory ALL (B-cell and T-cell)

Answer 41

both following >2 prior regimens. clofarabine (B-cell); nelarabine (T-cell), CR 18%