AML Flashcards
which syndromes are associated with AML
trisomy 21, monosomy 7 chromosome instability (FA, DC, Bloom) SCAN SDS DBA, CAMT NF-1, JMML PNH, SAA GATA2, CEBPA, RUNX1
What is the WHO classification for AML
1) BM myeloid blasts > 20%
OR
2) Recurrent cytogenetic abnormalities (no min blast count)
-t(8;21)(q22;q22), RUNX1-RUNX1T1 (CBFA2-AML1-ETO).
-inv(16)(p13.1;q22) or t(16;16)(p13.1;q22), CBFB-MYH11.
-APL with t(15;17)(q24;q21), PML-RARA.
-t(9;11)(p22;q23), MLLT3(AF9)-MLL.
-t(6;9)(p23;q34), DEK-NUP214.
-inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), RPN1-EVI1.
-t(1;22)(p13;q13), RBM15-MKL1.
-mutated NPM1.
-mutated CEBPA.
3) MDS-related
4) Therapy-related
5) Trisomy 21-related
6) Myeloid sarcoma
7) AML NOS - divide by FAB classification
AML High risk
therapy-related AML MDS-related AML Monosomy 5, monosomy 7,del5q FLT3/ITD with allelic ratio > 0.4 Induction failure MRD>0.1% at end Ind#1 (without low-risk cytogenetics)
AML Favourable risk
Down syndrome Inv 16 t(8;21) NPM or CEBPalpha mutation t(15;17) APL MRD negative at end induction 1 (1;11) - MLL-KMT2A *Note fav. genetics with MRD+ are still fav. risk
AML prognostic factors
Unfavorable:
- poor cytogenetics
- MRD positive
- high WBC count
UK AML Trials
MRC 10: ADE similar to DAT but more toxicity with thioguanine
MRC 12: MAE vs ADE. Mitox reduced relapse rate but no difference in EFS or OS. 4 courses = 5.
MRC 15: GO improves survival for patients with favourable cytogenetics
Adding Etop to AD does not change outcomes (adults)
BFM trials
BFM 93: ADE equals AIE - trend towards Ida
BFM98: HR-AML No difference in chemo vs alloHSCT
BFM 2004: L-dauno eq Idarubicin but higher dose of L-dauno. Less toxicity with L-dauno
North American trials
AAML 0531 - GO improves EFS for low-risk cyto, int-risk who got SCT from MSD and high-risk who got SCT. Intensity of CD33 expression key.
AML1031: Bortezomib in low-risk and sorafebib in FLT3-ITD
Immunophenotype
Pan myeloid: CD 13, 33, MPO (except M7) Monocytic: 11b, 14 Erythroid: Glycophorin A (235a) Megakaryocytic: 41a, 42, 61, absent MPO AP: autoflorence, bright CD33, HLA-dR neg, CD 43 neg t(8;21): often coexpress CD19
Prognostic factors in relapse
- Length of remission: 40% OS >1 yr vs 10%
- Molecular alterations at relapse: WT1 or FLT3-ITD
- No HSCT in CR1
- Response to therapy
What is the M2 FAB subtype associated with?
called AML with differentiation
t(8;21)
Can commonly present with chloromas
What is the M5 FAB subtype associated with?
called acute monocytic leukemia
Commonly presents with CNS involvement, gingival hyperplasia, chloromas and leukemia cutis
Commonly associated with MLL rearrangement
What are the 2 types of therapy related AML?
1) Alkylating agents and radiation:
•Long latency (5-7 years) from exposure, common preceding MDS
•Cytogenetics: -7, del(7q), -5, del(5q); complex cytogenetics
2) Topoisomerase II inhibitors (etoposide > anthracyclines)
•Short latency (1-2 years) from exposure, rare preceding MDS
•Cytogenetics: 11q23 rearrangements most common, but t(8;21), t(15;17), t(9;22) and inv(16) can also occur
What is differentiation syndrome?
Clinically will see: Fever, edema, pulm infiltrates, hypoxia, resp distress, hypotension, renal/hepatic dysfunction, effusions, rash
–Risk correlates with high WBC; can occur in absence of ATRA
–Rx: Prompt recognition and use of dexamethasone, hold ATRA until resolving
inv (16) and t(16;16) creates which chimeric protein
CBFB-MYH11 chimeric protein which is assoicated with a high rate of long-term remission
