Characteristics of patients with de novo AML with mutated NPM1 (N = 109)
| . | All patients (N = 109) . | NPM1 VAF ≤ 0.43 (n = 85) . | NPM1 VAF ≥ 0.44 (n = 24) . |
|---|---|---|---|
| Patient characteristics | |||
| Median age (range), y | 60 (15-83) | 60 (19-75) | 63 (15-83) |
| Male/female ratio | 0.84 | 0.79 | 1 |
| Clinical parameters | |||
| Median WBC (range), ×109/L | 24.0 (0.8-340) | 22.8 (0.8-340) | 44.3 (1.5-309) |
| Median PB blasts (range), % | 26 (0-98) | 26 (0-97) | 48 (1-98) |
| Median BM blasts (range), % | 71 (21-96) | 73 (21-95) | 70 (29-96) |
| Abnormal cytogenetics, N (%) | 14 (13) | 10 (12) | 4 (17) |
| Median NPM1 VAF (range) | 0.39 (0.04-0.54) | 0.38 (0.04-0.43) | 0.46 (0.44-0.54) |
| FLT3-ITD positive, N (%) | 42 (39) | 31 (36) | 11 (46) |
| Comutations by pathway, N (%) | |||
| DNA methylation | |||
| DNMT3A | 55 (50) | 45 (53) | 10 (42) |
| IDH1 | 24 (22) | 17 (20) | 7 (29) |
| IDH2 | 12 (11) | 11 (13) | 1 (4) |
| TET2 | 29 (27) | 26 (31) | 3 (13) |
| Epigenetic regulation | |||
| ASXL1 | 2 (2) | 2 (2) | 0 (0) |
| EZH2 | 0 (0) | 0 (0) | 0 (0) |
| BCOR | 2 (2) | 2 (2) | 0 (0) |
| SETBP1 | 0 (0) | 0 (0) | 0 (0) |
| BCORL | 1 (1) | 1 (1) | 0 (0) |
| SH2B3 | 2 (2) | 1 (1) | 1 (4) |
| SETD2 | 0 (0) | 0 (0) | 0 (0) |
| CREBBP | 1 (1) | 1 (1) | 0 (0) |
| Transcriptional regulation | |||
| WT1 | 7 (7) | 5 (6) | 2 (9) |
| PHF6 | 1 (1) | 1 (1) | 0 (0) |
| CEBPA | 5 (5) | 2 (2) | 3 (13) |
| RUNX1 | 1 (1) | 1 (1) | 0 (0) |
| ETV6 | 0 (0) | 0 (0) | 0 (0) |
| Cohesin complex | |||
| STAG2 | 2 (2) | 1 (1) | 1 (4) |
| PDS5B | 2 (2) | 1 (1) | 1 (4) |
| RAD21 | 4 (4) | 3 (4) | 1 (4) |
| RAS pathway | |||
| KRAS | 4 (4) | 4 (5) | 0 (0) |
| NRAS | 26 (24) | 23 (27) | 3 (13) |
| FLT3 (non-ITD) | 26 (24) | 19 (23) | 7 (29) |
| KIT | 1 (1) | 0 (0) | 1 (4) |
| CBL | 3 (3) | 2 (2) | 1 (4) |
| RIT1 | 4 (4) | 3 (4) | 1 (4) |
| PTPN11 | 26 (24) | 23 (27) | 3 (13) |
| NF1 | 3 (3) | 3 (4) | 0 (0) |
| JAK2 | 0 (0) | 0 (0) | 0 (0) |
| Spliceosome | |||
| U2AF1 | 0 (0) | 0 (0) | 0 (0) |
| ZRSR2 | 0 (0) | 0 (0) | 0 (0) |
| PRPF40b | 0 (0) | 0 (0) | 0 (0) |
| SRSF2 | 5 (5) | 4 (5) | 1 (4) |
| SF3B1 | 0 (0) | 0 (0) | 0 (0) |
| Other | |||
| CSF3R | 2 (2) | 1 (1) | 1 (4) |
| BRAF | 0 (0) | 0 (0) | 0 (0) |
| GATA2 | 1 (1) | 0 (0) | 1 (4) |
| TP53 | 0 (0) | 0 (0) | 0 (0) |
| Outcome, N (%) | |||
| Relapsed | 39 (36) | 24 (29) | 15 (63) |
| Alive at last follow-up | 73 (67) | 62 (74) | 10 (42) |
| Underwent SCT, N (%) | 59 (54) | 49 (58) | 10 (42) |
| SCT in CR1 | 45 (41) | 38 (45) | 7 (29) |
| Conditioning (all SCTs) | |||
| Reduced intensity | 36 (61) | 32 (65) | 4 (40) |
| Myeloablative | 23 (39) | 17 (35) | 6 (60) |
| SCT type (all SCTs), N (%) | |||
| Matched related donor | 18 (31) | 14 (29) | 4 (40) |
| Matched unrelated donor | 31 (53) | 27 (55) | 4 (40) |
| Mismatched unrelated donor | 3 (5) | 3 (6) | 0 (0) |
| Haploidentical | 5 (8) | 3 (6) | 2 (20) |
| Cord blood | 2 (3) | 2 (4) | 0 (0) |
| . | All patients (N = 109) . | NPM1 VAF ≤ 0.43 (n = 85) . | NPM1 VAF ≥ 0.44 (n = 24) . |
|---|---|---|---|
| Patient characteristics | |||
| Median age (range), y | 60 (15-83) | 60 (19-75) | 63 (15-83) |
| Male/female ratio | 0.84 | 0.79 | 1 |
| Clinical parameters | |||
| Median WBC (range), ×109/L | 24.0 (0.8-340) | 22.8 (0.8-340) | 44.3 (1.5-309) |
| Median PB blasts (range), % | 26 (0-98) | 26 (0-97) | 48 (1-98) |
| Median BM blasts (range), % | 71 (21-96) | 73 (21-95) | 70 (29-96) |
| Abnormal cytogenetics, N (%) | 14 (13) | 10 (12) | 4 (17) |
| Median NPM1 VAF (range) | 0.39 (0.04-0.54) | 0.38 (0.04-0.43) | 0.46 (0.44-0.54) |
| FLT3-ITD positive, N (%) | 42 (39) | 31 (36) | 11 (46) |
| Comutations by pathway, N (%) | |||
| DNA methylation | |||
| DNMT3A | 55 (50) | 45 (53) | 10 (42) |
| IDH1 | 24 (22) | 17 (20) | 7 (29) |
| IDH2 | 12 (11) | 11 (13) | 1 (4) |
| TET2 | 29 (27) | 26 (31) | 3 (13) |
| Epigenetic regulation | |||
| ASXL1 | 2 (2) | 2 (2) | 0 (0) |
| EZH2 | 0 (0) | 0 (0) | 0 (0) |
| BCOR | 2 (2) | 2 (2) | 0 (0) |
| SETBP1 | 0 (0) | 0 (0) | 0 (0) |
| BCORL | 1 (1) | 1 (1) | 0 (0) |
| SH2B3 | 2 (2) | 1 (1) | 1 (4) |
| SETD2 | 0 (0) | 0 (0) | 0 (0) |
| CREBBP | 1 (1) | 1 (1) | 0 (0) |
| Transcriptional regulation | |||
| WT1 | 7 (7) | 5 (6) | 2 (9) |
| PHF6 | 1 (1) | 1 (1) | 0 (0) |
| CEBPA | 5 (5) | 2 (2) | 3 (13) |
| RUNX1 | 1 (1) | 1 (1) | 0 (0) |
| ETV6 | 0 (0) | 0 (0) | 0 (0) |
| Cohesin complex | |||
| STAG2 | 2 (2) | 1 (1) | 1 (4) |
| PDS5B | 2 (2) | 1 (1) | 1 (4) |
| RAD21 | 4 (4) | 3 (4) | 1 (4) |
| RAS pathway | |||
| KRAS | 4 (4) | 4 (5) | 0 (0) |
| NRAS | 26 (24) | 23 (27) | 3 (13) |
| FLT3 (non-ITD) | 26 (24) | 19 (23) | 7 (29) |
| KIT | 1 (1) | 0 (0) | 1 (4) |
| CBL | 3 (3) | 2 (2) | 1 (4) |
| RIT1 | 4 (4) | 3 (4) | 1 (4) |
| PTPN11 | 26 (24) | 23 (27) | 3 (13) |
| NF1 | 3 (3) | 3 (4) | 0 (0) |
| JAK2 | 0 (0) | 0 (0) | 0 (0) |
| Spliceosome | |||
| U2AF1 | 0 (0) | 0 (0) | 0 (0) |
| ZRSR2 | 0 (0) | 0 (0) | 0 (0) |
| PRPF40b | 0 (0) | 0 (0) | 0 (0) |
| SRSF2 | 5 (5) | 4 (5) | 1 (4) |
| SF3B1 | 0 (0) | 0 (0) | 0 (0) |
| Other | |||
| CSF3R | 2 (2) | 1 (1) | 1 (4) |
| BRAF | 0 (0) | 0 (0) | 0 (0) |
| GATA2 | 1 (1) | 0 (0) | 1 (4) |
| TP53 | 0 (0) | 0 (0) | 0 (0) |
| Outcome, N (%) | |||
| Relapsed | 39 (36) | 24 (29) | 15 (63) |
| Alive at last follow-up | 73 (67) | 62 (74) | 10 (42) |
| Underwent SCT, N (%) | 59 (54) | 49 (58) | 10 (42) |
| SCT in CR1 | 45 (41) | 38 (45) | 7 (29) |
| Conditioning (all SCTs) | |||
| Reduced intensity | 36 (61) | 32 (65) | 4 (40) |
| Myeloablative | 23 (39) | 17 (35) | 6 (60) |
| SCT type (all SCTs), N (%) | |||
| Matched related donor | 18 (31) | 14 (29) | 4 (40) |
| Matched unrelated donor | 31 (53) | 27 (55) | 4 (40) |
| Mismatched unrelated donor | 3 (5) | 3 (6) | 0 (0) |
| Haploidentical | 5 (8) | 3 (6) | 2 (20) |
| Cord blood | 2 (3) | 2 (4) | 0 (0) |
BM, bone marrow; PB, peripheral blood.