Leukemia Flashcards
t(15;17)
PML:RARa; M3; APL
t(8;21) or inv(16)
CBF:RUNX1T1; M2; abnl eosinophilia; good prog
favorable prognosis markers: no need for trx
inv(16); t(8;21); t(15;17)
poor prognosis markers, need transplant
del(5q), -5, del(7q), -7, complex, 11q23
11q23
MLL gene: translocation with 11q23 bad
del5q del7q
associated with alkylators, poor prognosis group AML
FLT3 mutation
FLT-internal tandem repeat; poor prognosis ,
CEBPA mutation
favorable prognosis
induction
7+3: 90 dauno + 200 cytarabine x 7 days;
idarubicin
12mg/m2 for 3 days equivalent to 90 dauno
daunorubicin
90x3d = 50x5d
del5q MDS
lenalidomide if low/int-I risk
MDS cytopenia treatment
can use EPO
allotSCT for MDS
recommended for INT-2: cases include: poor karyotype and 5-10 blasts; poor karyotype and 2/3 cytopenias; good karyotype, 2/3 cytopenias and 11-20 blasts; 11-20 blasts;
IPSS
% blasts: 5-10- 0.5; 11-20: 1.5, 21+ 2. karyotype: intermediate 0.5; poor 1; cytopenia: 2/3 gets another 0.5 points.
MDS karyotypes
poor: complex or chromosome 7; good: 5q-, y-, 20q-
CLL karyotyping
13q- good
11- CLL
massive LAD out of proportion
17- CLL
higher richter transformation, resistance; consider up-front transplant
imatinib dosing
400mg/day; higher doses lead to increased cytogenetic CR but no difference in OS, PFS at 24mo
T315I
CML resistance mutation–> dasatinib/nilotinib doesn’t work
nilotinib dosing
400mg BID, higher CR compared to imatinib
dasatinib dosing
100mg day, higher CR compared to imatinib
gleevec failure
no heme response at 3 mo, no cytogenetic response at 6month, no partial at 12 month, no complete by 18 months
alkylating agent heme malignancies
del5q, del7q–> poor prognosis, 5-7yr latencies, also MDS
topoII associated maligngnices
11q23, 21q22, poor prognosis
ALL cells
+CD19 +CD200; 1/2 CD10+,
p190
ALL Ph translocation
ALL high risk types
t(4;11), t(8;14), t(1;19). Ph-positive(922)
gleevec response
major response: <35% metaphase in marrow
CML resistance
if no T315 or P-looop mutation, can consider increasing dose or using another TKI
Primary resistance in AML
if resistance following 7+3–>HIDAC, you can still proceed to transplant with 10-20% success rate
HTLV-1
T-cell leukemia causative- endemic in Caribbean, Japan (sexual contact, blood, mat/fet). 2-4% of infected will get leukemia
benzene
can cause AML or myelodysplasia
alkylator-associated MDS/AML cytogenetics
-5, -7, +8; develop 4-6 years after exposure, low response rates
topoisomerase inhibitor AML
no MDS phase, 1-2 year latency, 11q23 abel, or 21q22 translocation.
NPM1 mutation without FLT3 mut
good risk
Preparative regimens for AML for AlloSCT
1) CY 60mg/kg x 2 + TBI 10-14Gy/3-6D. or 120mg/kg with oral busulifan 16mg/kg
reduced intensity conditioning AlloSCT for >60
cannot use if active relapsed disease. otherwise encouraging with less toxicity
APL treatment by risk factor
WBC give ATRA–>consolidate with ATRA/ArO3 (consider omitting chemo); if WBC>10–> high risk need all three
anthracycline-associated AML
APL type, t(15;17)
topoisomerase associated AML
no MDS, 11q23/21q22, short latency (6mo-3yr)
myeloperox or nonspecific esterase
AML stains. Negative in ALL
p190bcr-abl
associated with ALL
p210bcr-abl
associated with CML (and some ALL)
ALL standard therapy
vincristine, prednisone, anthracycline, asparaginase
Ph-positive ALL
add a TKI.
mature B-cell ALL
add rituximab
ALL CNS prophylaxis
necessary. high risk: high WBC count or high LDH. trophy reduces risk to
ALL consolidation therapy
high dose MTX, cytarabine, CY and anthracycline
ALL maintenance therapy
low dose MTX, 6-MP, vincristine, predinsone
good risk ALL
hyperdiploidy, or del(9p)
ALL risk factors
Poor risk: age>35, >30WBC, pro B-cell, bad cytogenetics, >wks to CR
transplant for ALL
all patients should get if
elderly with Ph-positive ALL
can consider dasatinib+prednisone
recurrent T-cell ALL therapy
nelarabine–>40% CR
mature B-cell ALL (Burkitt’s)
improved prognosis with high dose MTX, cytarabine, rituximab
