Clinical and genetic characteristics of 1770 younger adult patients with AML according to DNMT3A mutation status
Characteristic . | DNMT3Awt (n = 1400) . | All DNMT3Amut (n = 370) . | P* . | R882-DNMT3Amut (n = 239) . | non-R882 DNMT3Amut (n = 131) . | P† . | ||||
---|---|---|---|---|---|---|---|---|---|---|
No. . | % . | No. . | % . | No. . | % . | No. . | % . | |||
Age, years | ||||||||||
Median | 47.6 | 50.5 | <.0001 | 49.9 | 51.2 | .19 | ||||
Range | 18-60 | 18-60 | 18-60 | 27-60 | ||||||
Sex | ||||||||||
Male | 747 | 53.4 | 160 | 43.2 | .0006 | 102 | 42.7 | 58 | 44.3 | .83 |
Female | 653 | 46.6 | 210 | 56.8 | 137 | 57.3 | 73 | 55.7 | ||
WBC, g/l | ||||||||||
Median | 10.3 | 24.5 | <.0001 | 32.1 | 2.1 | .16 | ||||
Range | 0.2-372 | 0.2-532 | 0.2-427 | 0.7-532.7 | ||||||
Missing values | 20 | 4 | 2 | 2 | ||||||
LDH, U/l | ||||||||||
Median | 413.5 | 496 | .0004 | 493 | 496 | .68 | ||||
Range | 84-15 098 | 137-6907 | 145-5438 | 137-6907 | ||||||
Missing values | 40 | 5 | 3 | 2 | ||||||
BM blasts (%) | ||||||||||
Median | 73 | 80 | <.0001 | 80 | 80 | .93 | ||||
Range | 2-100 | 2-100 | 2-100 | 4-100 | ||||||
Missing values | 106 | 30 | 22 | 8 | ||||||
PB blasts (%) | ||||||||||
Median | 36 | 34.5 | .59 | 30 | 43.5 | .16 | ||||
Range | 0-100 | 0-99 | 0-99 | 0-99 | ||||||
Missing values | 106 | 26 | 15 | 11 | ||||||
Platelet counts, g/l | ||||||||||
Median | 49 | 70 | <.0001 | 73 | 65 | .15 | ||||
Range | 2-993 | 5-916 | 5-764 | 10-916 | ||||||
Missing values | 20 | 5 | 3 | 2 | ||||||
Hemoglobin, g/l | ||||||||||
Median | 9 | 9.1 | .22 | 9.0 | 9.3 | .32 | ||||
Range | 2.5-17.6 | 4.7-15.0 | 4.7-15.0 | 5.4-14.7 | ||||||
Missing values | 20 | 6 | 3 | 3 | ||||||
Cytogenetic classification‡ | ||||||||||
Favorable risk | 252 | 19.6 | 4 | 1.1 | <.0001 | 0 | 4§ | 3.2 | <.0001 | |
Intermediate risk | 751 | 58.2 | 309 | 89.4 | 212 | 95.1 | 97 | 78.9 | ||
Adverse risk | 287 | 22.2 | 33 | 9.5 | 11 | 4.9 | 22 | 17.9 | ||
Normal karyotype | 526 | 40.8 | 268 | 77.5 | <.0001 | 187 | 83.9 | 81 | 65.9 | .0002 |
inv(3)/t(3;3) | 26 | 2.0 | 4 | 1.2 | .37 | 0 | 4 | 3.3 | .02 | |
t(6;9) | 14 | 1.1 | 1 | 0.3 | .23 | 0 | 1 | 0.8 | .36 | |
t(9;11) | 27 | 2.0 | 0 | .003 | 0 | 0 | ||||
t(var;11q23) | 27 | 2.0 | 3 | 0.9 | .18 | 0 | 3 | 2.4 | .04 | |
trisomy 8 (noncomplex) | 62 | 4.8 | 17 | 4.9 | .89 | 8 | 3.6 | 9 | 7.3 | .19 |
Complex | 162 | 12.6 | 13 | 3.8 | .009 | 5 | 2.2 | 8 | 6.5 | .07 |
Missing values | 110 | 24 | 16 | 8 | ||||||
NPM1 | ||||||||||
Mutated | 241 | 17.8 | 234 | 64 | <.0001 | 171 | 72.1 | 63 | 49.2 | <.0001 |
Missing values | 46 | 5 | 2 | 3 | ||||||
CEBPA | ||||||||||
Mutated (double/single) | 74/31 | 6.2/2.6 | 3/15 | 0.9/4.6 | .007 | 2/12 | 0.9/5.6 | 1/3 | 0.8/2.7 | .32 |
Missing values | 225 | 44 | 25 | 19 | ||||||
FLT3-ITD | ||||||||||
Mutated | 261 | 19 | 126 | 34.6 | <.0001 | 91 | 38.2 | 35 | 26.7 | .04 |
Missing values | 28 | 4 | 1 | 3 | ||||||
FLT3-TKD | ||||||||||
Mutated | 97 | 7.3 | 28 | 7.9 | .73 | 17 | 7.3 | 11 | 9 | .68 |
Missing values | 68 | 16 | 7 | 9 | ||||||
IDH1/IDH2 | ||||||||||
Mutated | 151 | 12.1 | 96 | 28.7 | <.0001 | 57 | 26.4 | 39 | 32.8 | .26 |
IDH1R132 | 62 | 37 | .0002 | 24 | 13 | .99 | ||||
IDH2R140 | 65 | 37 | .0004 | 22 | 15 | .59 | ||||
IDH2R172 | 24 | 22 | <.0001 | 11 | 11 | .17 | ||||
Missing values | 154 | 35 | 23 | 12 | ||||||
Type of AML | ||||||||||
De novo AML | 1243 | 89 | 344 | 93.2 | .032 | 227 | 95 | 117 | 89.3 | .11 |
Secondary AML | 61 | 4.4 | 13 | 3.5 | 5 | 2.1 | 8 | 6.1 | ||
Therapy-related AML | 92 | 6.6 | 12 | 3.3 | 7 | 2.9 | 5 | 3.8 | ||
Missing values | 4 | 1 | 1 |
Characteristic . | DNMT3Awt (n = 1400) . | All DNMT3Amut (n = 370) . | P* . | R882-DNMT3Amut (n = 239) . | non-R882 DNMT3Amut (n = 131) . | P† . | ||||
---|---|---|---|---|---|---|---|---|---|---|
No. . | % . | No. . | % . | No. . | % . | No. . | % . | |||
Age, years | ||||||||||
Median | 47.6 | 50.5 | <.0001 | 49.9 | 51.2 | .19 | ||||
Range | 18-60 | 18-60 | 18-60 | 27-60 | ||||||
Sex | ||||||||||
Male | 747 | 53.4 | 160 | 43.2 | .0006 | 102 | 42.7 | 58 | 44.3 | .83 |
Female | 653 | 46.6 | 210 | 56.8 | 137 | 57.3 | 73 | 55.7 | ||
WBC, g/l | ||||||||||
Median | 10.3 | 24.5 | <.0001 | 32.1 | 2.1 | .16 | ||||
Range | 0.2-372 | 0.2-532 | 0.2-427 | 0.7-532.7 | ||||||
Missing values | 20 | 4 | 2 | 2 | ||||||
LDH, U/l | ||||||||||
Median | 413.5 | 496 | .0004 | 493 | 496 | .68 | ||||
Range | 84-15 098 | 137-6907 | 145-5438 | 137-6907 | ||||||
Missing values | 40 | 5 | 3 | 2 | ||||||
BM blasts (%) | ||||||||||
Median | 73 | 80 | <.0001 | 80 | 80 | .93 | ||||
Range | 2-100 | 2-100 | 2-100 | 4-100 | ||||||
Missing values | 106 | 30 | 22 | 8 | ||||||
PB blasts (%) | ||||||||||
Median | 36 | 34.5 | .59 | 30 | 43.5 | .16 | ||||
Range | 0-100 | 0-99 | 0-99 | 0-99 | ||||||
Missing values | 106 | 26 | 15 | 11 | ||||||
Platelet counts, g/l | ||||||||||
Median | 49 | 70 | <.0001 | 73 | 65 | .15 | ||||
Range | 2-993 | 5-916 | 5-764 | 10-916 | ||||||
Missing values | 20 | 5 | 3 | 2 | ||||||
Hemoglobin, g/l | ||||||||||
Median | 9 | 9.1 | .22 | 9.0 | 9.3 | .32 | ||||
Range | 2.5-17.6 | 4.7-15.0 | 4.7-15.0 | 5.4-14.7 | ||||||
Missing values | 20 | 6 | 3 | 3 | ||||||
Cytogenetic classification‡ | ||||||||||
Favorable risk | 252 | 19.6 | 4 | 1.1 | <.0001 | 0 | 4§ | 3.2 | <.0001 | |
Intermediate risk | 751 | 58.2 | 309 | 89.4 | 212 | 95.1 | 97 | 78.9 | ||
Adverse risk | 287 | 22.2 | 33 | 9.5 | 11 | 4.9 | 22 | 17.9 | ||
Normal karyotype | 526 | 40.8 | 268 | 77.5 | <.0001 | 187 | 83.9 | 81 | 65.9 | .0002 |
inv(3)/t(3;3) | 26 | 2.0 | 4 | 1.2 | .37 | 0 | 4 | 3.3 | .02 | |
t(6;9) | 14 | 1.1 | 1 | 0.3 | .23 | 0 | 1 | 0.8 | .36 | |
t(9;11) | 27 | 2.0 | 0 | .003 | 0 | 0 | ||||
t(var;11q23) | 27 | 2.0 | 3 | 0.9 | .18 | 0 | 3 | 2.4 | .04 | |
trisomy 8 (noncomplex) | 62 | 4.8 | 17 | 4.9 | .89 | 8 | 3.6 | 9 | 7.3 | .19 |
Complex | 162 | 12.6 | 13 | 3.8 | .009 | 5 | 2.2 | 8 | 6.5 | .07 |
Missing values | 110 | 24 | 16 | 8 | ||||||
NPM1 | ||||||||||
Mutated | 241 | 17.8 | 234 | 64 | <.0001 | 171 | 72.1 | 63 | 49.2 | <.0001 |
Missing values | 46 | 5 | 2 | 3 | ||||||
CEBPA | ||||||||||
Mutated (double/single) | 74/31 | 6.2/2.6 | 3/15 | 0.9/4.6 | .007 | 2/12 | 0.9/5.6 | 1/3 | 0.8/2.7 | .32 |
Missing values | 225 | 44 | 25 | 19 | ||||||
FLT3-ITD | ||||||||||
Mutated | 261 | 19 | 126 | 34.6 | <.0001 | 91 | 38.2 | 35 | 26.7 | .04 |
Missing values | 28 | 4 | 1 | 3 | ||||||
FLT3-TKD | ||||||||||
Mutated | 97 | 7.3 | 28 | 7.9 | .73 | 17 | 7.3 | 11 | 9 | .68 |
Missing values | 68 | 16 | 7 | 9 | ||||||
IDH1/IDH2 | ||||||||||
Mutated | 151 | 12.1 | 96 | 28.7 | <.0001 | 57 | 26.4 | 39 | 32.8 | .26 |
IDH1R132 | 62 | 37 | .0002 | 24 | 13 | .99 | ||||
IDH2R140 | 65 | 37 | .0004 | 22 | 15 | .59 | ||||
IDH2R172 | 24 | 22 | <.0001 | 11 | 11 | .17 | ||||
Missing values | 154 | 35 | 23 | 12 | ||||||
Type of AML | ||||||||||
De novo AML | 1243 | 89 | 344 | 93.2 | .032 | 227 | 95 | 117 | 89.3 | .11 |
Secondary AML | 61 | 4.4 | 13 | 3.5 | 5 | 2.1 | 8 | 6.1 | ||
Therapy-related AML | 92 | 6.6 | 12 | 3.3 | 7 | 2.9 | 5 | 3.8 | ||
Missing values | 4 | 1 | 1 |
n, number of patients; WBC, white blood cell count; LDH, lactate dehydrogenase; BM, bone marrow; PB, peripheral blood; TKD, tyrosine kinase domain; t, therapy-related.
Based on the European LeukemiaNet (ELN) guidelines.21
Comparison of DNMT3Awt vs DNMT3Amut.
Comparison of R882-DNMT3Amut vs non- R882-DNMT3Amut.
n = 2, inv(16); n = 1, t(8;21); n = 1, t(15;17).