Characteristics of patients with de novo AML with DNMT3AMUT (N = 104)
| . | DNMT3AMUT, N = 104 . | DNMT3ALOW, N = 57 . | DNMT3AHIGH, N = 47 . | P* . |
|---|---|---|---|---|
| Patient characteristics | ||||
| Median age (range), y | 61 (23-87) | 60 (23-87) | 62 (30-87) | >.05 |
| M:F ratio | 0.86 | 0.90 | 0.81 | >.05 |
| Abnormal karyotype, N (%) | 19 (18) | 9 (16) | 10 (21) | >.05 |
| Treatment | ||||
| Induction chemotherapy, N (%) | 93 (89) | 52 (91) | 41 (87) | >.05 |
| FLT3-inhibitor therapy, N (%) | 5 (5) | 5 (9) | 0 | >.05 |
| Allo-SCT, N (%) | 59 (57) | 38 (67) | 21 (45) | .0243 |
| Median time from diagnosis to allo-SCT (range), mo | 4.5 (2-66.5) | 4.4 (2-36.5) | 4.9 (2.1-66.5) | >.05 |
| Outcome | ||||
| Achieved complete remission, N (%) | 83 (89) | 48 (92) | 35 (85) | >.05 |
| Relapsed, N (%) | 45 (48) | 20 (39) | 25 (61) | .0311 |
| Alive at last follow-up, N (%) | 55 (59) | 37 (71) | 18 (44) | .0076 |
| Median EFS (range), mo | 25.2 (0.7-83.3) | 56.8 (1.1-83.3) | 14.1 (0.7-73.8) | .0154 |
| Median OS (range), mo | 44.5 (0.7-83.3) | NR (1.1-83.3) | 18.3 (0.7-73.8) | .0011 |
| DNMT3A mutation | ||||
| Two DNMT3A mutations, N (%) | 13 (14) | 7 (12) | 6 (13) | >.05 |
| Type of DNMT3A mutations, N (%) | ||||
| Missense mutations | 80 (77) | 41 (72) | 39 (83) | >.05 |
| • R882H | 39 (38) | 18 (32) | 21 (45) | >.05 |
| • R882C | 11 (11) | 6 (11) | 5 (11) | >.05 |
| • R882P | 3 (3) | 0 | 3 (6) | |
| • Others | 29 (28) | 17 (30) | 12 (26) | >.05 |
| Nonsense mutations | 9 (9) | 5 (9) | 4 (9) | >.05 |
| Frameshift mutations | 12 (12) | 9 (16) | 3 (6) | >.05 |
| Splice site mutations | 2 (2) | 2 (4) | 0 | >.05 |
| Clinical parameters | ||||
| Median Hb (range), g/dL | 8.8 (3.7-15) | 8.7 (5.7-12.5) | 8.8 (3.7-15) | >.05 |
| Median platelets (range), ×103/µL | 84 (12-543) | 99 (18-543) | 64.5 (12-271) | >.05 |
| Median WBC (range), ×109/L | 13.8 (0.6-220) | 5.6 (0.6-174) | 37 (0.6-220) | <.0001 |
| Median PB blasts (range), % | 16 (0-98) | 11 (0-88) | 24 (0-98) | .0093 |
| Median BM blasts (range), % | 65.5 (20-96) | 60 (20-90) | 70 (22-96) | .0086 |
| WHO classification, N (%) | ||||
| AML, NOS | 34 (33) | 23 (40) | 11 (23) | >.05 |
| AML-MRC | 7 (7) | 4 (7) | 3 (6) | >.05 |
| AML with NPM1 mutation | 54 (52) | 26 (46) | 28 (60) | >.05 |
| AML with RUNX1 mutation | 9 (9) | 4 (7) | 5 (11) | >.05 |
| Morphologic parameters | ||||
| Erythroid dysplasia | ||||
| Mean dysplasia, % | 28 | 25 | 33 | >.05 |
| Mean megaloblastic change | 0.9 | 0.9 | 1.0 | >.05 |
| Mean multinucleation | 0.7 | 0.6 | 0.8 | >.05 |
| Mean nuclear irregularities | 1.5 | 1.3 | 1.7 | >.05 |
| Granulocytic dysplasia | ||||
| Mean dysplasia, % | 27 | 18 | 35 | .0177 |
| Mean abnormal nuclear shape | 1.0 | 0.7 | 1.3 | .0082 |
| Mean hypogranulation | 1.2 | 0.9 | 1.5 | .0201 |
| Megakaryocytic dysplasia | ||||
| Mean dysplasia, % | 44 | 38 | 49 | >.05 |
| Mean micromegakaryocytes | 1.2 | 1.0 | 1.4 | >.05 |
| Mean separated nuclear lobes | 1.2 | 1.2 | 1.2 | >.05 |
| Mean hypolobated nuclei | 1.4 | 1.4 | 1.4 | >.05 |
| . | DNMT3AMUT, N = 104 . | DNMT3ALOW, N = 57 . | DNMT3AHIGH, N = 47 . | P* . |
|---|---|---|---|---|
| Patient characteristics | ||||
| Median age (range), y | 61 (23-87) | 60 (23-87) | 62 (30-87) | >.05 |
| M:F ratio | 0.86 | 0.90 | 0.81 | >.05 |
| Abnormal karyotype, N (%) | 19 (18) | 9 (16) | 10 (21) | >.05 |
| Treatment | ||||
| Induction chemotherapy, N (%) | 93 (89) | 52 (91) | 41 (87) | >.05 |
| FLT3-inhibitor therapy, N (%) | 5 (5) | 5 (9) | 0 | >.05 |
| Allo-SCT, N (%) | 59 (57) | 38 (67) | 21 (45) | .0243 |
| Median time from diagnosis to allo-SCT (range), mo | 4.5 (2-66.5) | 4.4 (2-36.5) | 4.9 (2.1-66.5) | >.05 |
| Outcome | ||||
| Achieved complete remission, N (%) | 83 (89) | 48 (92) | 35 (85) | >.05 |
| Relapsed, N (%) | 45 (48) | 20 (39) | 25 (61) | .0311 |
| Alive at last follow-up, N (%) | 55 (59) | 37 (71) | 18 (44) | .0076 |
| Median EFS (range), mo | 25.2 (0.7-83.3) | 56.8 (1.1-83.3) | 14.1 (0.7-73.8) | .0154 |
| Median OS (range), mo | 44.5 (0.7-83.3) | NR (1.1-83.3) | 18.3 (0.7-73.8) | .0011 |
| DNMT3A mutation | ||||
| Two DNMT3A mutations, N (%) | 13 (14) | 7 (12) | 6 (13) | >.05 |
| Type of DNMT3A mutations, N (%) | ||||
| Missense mutations | 80 (77) | 41 (72) | 39 (83) | >.05 |
| • R882H | 39 (38) | 18 (32) | 21 (45) | >.05 |
| • R882C | 11 (11) | 6 (11) | 5 (11) | >.05 |
| • R882P | 3 (3) | 0 | 3 (6) | |
| • Others | 29 (28) | 17 (30) | 12 (26) | >.05 |
| Nonsense mutations | 9 (9) | 5 (9) | 4 (9) | >.05 |
| Frameshift mutations | 12 (12) | 9 (16) | 3 (6) | >.05 |
| Splice site mutations | 2 (2) | 2 (4) | 0 | >.05 |
| Clinical parameters | ||||
| Median Hb (range), g/dL | 8.8 (3.7-15) | 8.7 (5.7-12.5) | 8.8 (3.7-15) | >.05 |
| Median platelets (range), ×103/µL | 84 (12-543) | 99 (18-543) | 64.5 (12-271) | >.05 |
| Median WBC (range), ×109/L | 13.8 (0.6-220) | 5.6 (0.6-174) | 37 (0.6-220) | <.0001 |
| Median PB blasts (range), % | 16 (0-98) | 11 (0-88) | 24 (0-98) | .0093 |
| Median BM blasts (range), % | 65.5 (20-96) | 60 (20-90) | 70 (22-96) | .0086 |
| WHO classification, N (%) | ||||
| AML, NOS | 34 (33) | 23 (40) | 11 (23) | >.05 |
| AML-MRC | 7 (7) | 4 (7) | 3 (6) | >.05 |
| AML with NPM1 mutation | 54 (52) | 26 (46) | 28 (60) | >.05 |
| AML with RUNX1 mutation | 9 (9) | 4 (7) | 5 (11) | >.05 |
| Morphologic parameters | ||||
| Erythroid dysplasia | ||||
| Mean dysplasia, % | 28 | 25 | 33 | >.05 |
| Mean megaloblastic change | 0.9 | 0.9 | 1.0 | >.05 |
| Mean multinucleation | 0.7 | 0.6 | 0.8 | >.05 |
| Mean nuclear irregularities | 1.5 | 1.3 | 1.7 | >.05 |
| Granulocytic dysplasia | ||||
| Mean dysplasia, % | 27 | 18 | 35 | .0177 |
| Mean abnormal nuclear shape | 1.0 | 0.7 | 1.3 | .0082 |
| Mean hypogranulation | 1.2 | 0.9 | 1.5 | .0201 |
| Megakaryocytic dysplasia | ||||
| Mean dysplasia, % | 44 | 38 | 49 | >.05 |
| Mean micromegakaryocytes | 1.2 | 1.0 | 1.4 | >.05 |
| Mean separated nuclear lobes | 1.2 | 1.2 | 1.2 | >.05 |
| Mean hypolobated nuclei | 1.4 | 1.4 | 1.4 | >.05 |
Bold P values represent < .05.
allo-SCT, allogeneic SCT; Hb, hemoglobin; NOS, not otherwise specified; NR, not reached; PB, peripheral blood.
P values comparing DNMT3AHIGH and DNMT3ALOW groups.