Leukemia Flashcards
Epidemiology
13780 new AML cases, 10200 deaths, inc exponentially after 50 y/o
WHO definition
20% myeloid blasts in peripheral blood of BM; except if t(15;17), t(8;21), inv(16), t(16;16)
FAB classification
M0-M7; M3=APML
WHO classification
I. AML with recurrent genetic abnormalities
II. AML with MDS related changes
III. Therapy-related neoplasm
IV. AML not otherwise specified
AML - Better Risk 5 yr OS 55-65%
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
AML - Intermediate Risk 5 yr OS 24-40%
Normal cytogenetics, +8 only, t(9;11) –MM: t(8;21), Inv (16), f(16;16) with c-KIT mutation
AML - Poor Risk 5 yr OS 5-14%
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
signs and symptoms
bone marrow failure(anemia-fatigue, weakness, CV effects; thrombocyto- bleeding; neutropenia- infx), extramedullary tissue invasion, leukostasis secondary to high WBC, TLS, chloroma (skin)
When to use daunorubicin 90mg/m2 vs 45 in 7+3; NEJM 2009 study
good or intermediate risk OR less than 50y/o. improves CR 57.3->70.6, OS 15.7->23.7mo
CR criteria
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
Treatment related problems
bone marrow suppression, TLS, N/V, organ toxicities, Mucositis/ stomatitis, Nutrition
Mgmt of thrombocytopenia
menses suppression, stress ulcer px, acute bleeding treatment
Induction tx evaluation Day 14-17 BMBx; significant residual blasts OR significant cytoreduction with residual blasts
re-induction 7+3
Induction tx evaluation Day 14-17 BMBx; BM is hypoplastic
delay re-induction until status of marrow is clear
why dose reduce araC from 3 to 1.5gm/m2 in those >60yo?
neurotoxicity
post remission tx -favorable (better and intermediate) risk, better tolerated if <60yo
HD araC
post remission tx -poor risk
allogeneic HSCT
relapse tx
clinical trial prefered, if late relapse (>12mo) consider re-induction, if not salvage chemo then alloHSCT, best supportive care if not tx candidate
> 60 yo
best course not known - can do best supportive care (hydrea, transfusions), std 7+3, or reduced intensity chemo (aza, decit)
APML
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”
APML risks and CR
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)
ATRA toxicities
differentiation sx, HA, mucosal dryness, hyperleukocytosis
APML and coagulopathies
plt >30k, fibrinogen >100 (cryo, FFP), hyperleukocytosis (start chemo other than ATRA)
APML induction
ATRA + ida or dauno
APML consolidation
ida or dauno x 2 cycle + ATRA (if high risk WBC >10k add araC)
APML maintenance
ATRA + weekly MTX +/- 6-MP x 1-2 years
arsenic trioxide
excellent outcomes in refractory pts, may play a role in consolidation, may use in induction for those that can not tolerate anthracycline
arsenic trioxide toxicity
QTc, Mg++, K+
ATRA differentiation sx
respiratory distress, fever, pulm infiltrates, weight gain, renal failure, hypotension
ATRA differentiation sx management
dex IV 10mg q12h x3d (minimum), continue ATRA unless severe, then hold until resolves then restart ATRA
ALL signs and symptoms
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)
ALL classification
> 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
ALL unfavorable prognostic factors
Age >55yo, WBC >30k (>100k in T-cell), t(9;22), delayed time to induction of CR, CNS involvement, minimal resdidual dz after induction
ALL induction - std
vincristine + anthracycline + corticosteroids; if poor prognostic ADD asparaginase, cyclophos, araC, and MTX; CNS px
ALL induction - hyperCVAD + maintenance
hyperCVAD x8 cycles; CNS px; maintenance (risk stratified): 6MP, vincrisitine, MTX, pred
TLS - high risk - hydration + rasburicase
Burkitt’s, B-ALL, ALL with WBC >100k, AML >50k or monoblastic
TLS - intermediate risk - hydration + allopurinol, consider rasburicase in peds
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)
rasburicase - peds dosing
0.15-0.2 mg/kg IV daily (up to 7 days); pros: works in 2-4hrs; cons: cost, hypersensitivity
ALL - Ph+
imatinib + hyperCVAD CR >90% (before TKIs was <20%) - can also use dasatinib 1st line; alloSCT only chance of cure, but use is debated
refractory ALL - Ph+
ponatinib
relapsed / refractory ALL (B-cell and T-cell)
both following >2 prior regimens. clofarabine (B-cell); nelarabine (T-cell), CR 18%
