Blood Cell counts (% peripheral blood blast) / Previous
Therapy
AML#11 / 54 yrs/male / M5 AML
FLT3-ITD + / Normal / 68.5K (90%) with 94% marrow blasts / None
AML#21,2 / 74 yrs/female / AML (relapse)
mutant FLT3 +
mutant NPM1 + / chromosomes 46xy with 1:15 translocation / 3.4 (71%)
(marrow blast N/A) / 3+7 RIC allo in CRI
PKC412/RAD001 clinical trial
sorafenib
decitabine
AML#3 / 74 yrs/female / AML (M1)
mutant NPM1 +
FLT3-ITD + / Normal / 28.7 (34%) with 70% marrow blasts / None
AML#4 / 55 yrs/male / AML (primary refractory)
FLT3-ITD +
mutant NPM1 + / Normal / 23.7 (74%) with 69% marrow blasts / 3+7, 2+5
AML#5 / 68 yrs/male / AML (refractory, relapse)
FLT3-ITD +
wt NPM1 / Normal / 9.0 (59%) with 77% marrow blasts / 3+7+consolid X2
(2+5, mid dose ara-c)
MEC
PKC412/RAD001
AML#6 / 62 yrs/female / AML (relapse)
FLT3-ITD +
mutant NPM1 + / T(1;12;17) / 52.9 (57%) with 88% marrow blasts / 3+7+consolid X 3
(2+5 mid dose ara-c X 2)
AML#72 / 54 yrs/male / AML (relapse)
FLT3-ITD + / t(1;5)
del 13t (13;14)
del 14q
del 15q
del 20q / 7.3 (20%)
(marrow blasts N/A) / 3+7 consolid X 4
(high dose ara-c X 4)
MEC
alloSCT
AML#8 / 48 yrs/male / AML (primary refractory)
FLT3-ITD +
wt NPM1 / +8 / 7.5 (36%) (marrow blasts N/A) / 3+7, 2+5
MEC
AML#9
(cm68252)
AML#102 / 68 yrs/male / AML (M2)
FLT3-ITD+
mutant NPM1 + / Normal / 120 (64%) with 67% marrow blasts / None
AML#112 / 24 yrs/female / AML (AMML) (M4)
unknown FLT3 status / inv16 / 33.6 (36%) with 20% marrow blasts / None
AML#122 / 77 yrs/male / AML (M1)
unknown FLT3 status / Very complex
1+, 8+, 10++
11+, 13+, 17+
17-, 21+, 22+ / 3.0 (66%) with 84% marrow blasts / None
AML#13
AML#14
(cm69223) / 69 yrs/female / mixed phenotype acute leukemia, T/myeloid
wt FLT3
wt NPM1 / dic t(12;17) / 3.6 (18%) with 90% marrow blasts / Amonafide/Ara-c,
Ara-c consolidation
AML#15
Cm72587 / 65 yrs/female / AML (M1)
wt FLT3
wt NPM1 / Complex
del 5q
del 7
del 12 / 3.3 (74%)
with 61% marrow blasts / Treatment-resistant AML
ida/Ara-c/lenalidomide
RIC allo Flud/busulfan/ATG
AML#16 / 71 yrs/female / AML (M1)
wt FLT3 / Complex
del 5q
del 7 / 5.3 (9%)
with 25% marrow blasts / None
AML#17 / 63 yrs/male / AML
wt FLT3 / Normal / 6.4 (72%)
with ND marrow blasts / thal/lenalidomide
3+7
allo SCT
AML#18
(cm71072) / 57 yrs/male / AML (M1)
wt FLT3
wt NPM1 / Normal / 5.2 (82%) with 95% marrow blasts / 3+7, MEC,
Clofarabine/Ara-c,
Busulfan/cyclosphosphamide,
Allo-SCT, decitabine,
High dose Ara-c,
DLI, lenalidomide/bortezomib
AML#19 / 69 yrs/male / AML (M0)
wt FLT3
wt NPM1 / Pentasom 8
(3 extra 8) / 12 (61%) with 82% marrow blasts / None
Supplementary Table I. AML patient information.
MEC= mitoxantrone/etoposide/Ara-c
DLI= donor lymphocyte infusion
allo-SCT= allogeneic stem cell transplant
ATG = anti-thymocyte globulin
RIC = reduced intensity conditioning
1Weisberg E, Liu Q, Nelson E, Kung AL, Christie AL, Bronson R, et al. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors. Leukemia 2012;26:2233-44.
2Weisberg E, Liu Q, Zhang Z, Nelson E, Sattler M, Liu F, et al. Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells. PLoS One 2013;8:e56473.