Baseline characteristics, early mortality, achievement of CR/CRi, and timing of allogeneic transplant, by disease group
| Number∗ . | De novo (dn) NPM1 AML . | t-NPM1 AML . | t-AML . | P value . | |
|---|---|---|---|---|---|
| 2394 . | 96 . | 390 . | t-NPM1 AML vs dn-NPM1 AML . | t-NPM1 AML vs t-AML . | |
| Age, median (IQR) | 56.00 (47.00-64.00) | 65.00 (58.00-69.25) | 60.00 (52.00-67.00) | <.001 | <.001 |
| Female (%) | 1291 (54%) | 62 (65%) | 251 (64%) | .047 | >.99 |
| Previous therapy | NA | <.001 | |||
| Chemotherapy ± radiotherapy | NA | 55 (57%) | 312 (80%) | ||
| Radiotherapy alone | NA | 41 (43%) | 78 (20%) | ||
| Indication for cytotoxic therapy | NA | .18 | |||
| Hematological | NA | 17 (18%) | 89 (23%) | ||
| Solid tumor | NA | 63 (66%) | 254 (65%) | ||
| Nonmalignant | NA | 9 (9.4%) | 16 (4.1%) | ||
| Unknown | NA | 7 (7.3%) | 31 (7.9%) | ||
| Latency between chemo/radiotherapy and AML, median years (IQR) | NA | 5.00 (3.00-10.00) | 4.00 (2.00-9.00) | NA | .34 |
| Year of diagnosis | .90 | .32 | |||
| Before 2011 | 1300 (54%) | 52 (54%) | 204 (52%) | ||
| 2011-2015 | 706 (29%) | 27 (28%) | 135 (35%) | ||
| After 2015 | 388 (16%) | 17 (18%) | 51 (13%) | ||
| Blood counts at diagnosis | |||||
| WCC, median (IQR) | 28.40 (8.00-70.22) | 31.95 (10.03-63.60) | 4.82 (2.00-22.01) | .67 | <.001 |
| Missing (n) | 22 | 5 | 8 | ||
| Platelets, median (IQR) | 63.00 (37.00-111.00) | 63.00 (36.75-118.50) | 46.50 (25.00-90.00) | .92 | .012 |
| Missing (n) | 38 | 7 | 10 | ||
| BM blast %, median (IQR) | 74.00 (50.00-89.00) | 76.00 (54.50-86.00) | 50.00 (30.75-79.00) | .69 | <.001 |
| Missing (n) | 175 | 9 | 27 | ||
| Karyotype | |||||
| Normal karyotype | 1986 (88%) | 78 (88%) | 103 (28%) | .51 | <.001 |
| Favorable | 0 (0%) | 0 (0%) | 45 (12%) | ||
| Other intermediate | 254 (11%) | 9 (10%) | 87 (24%) | ||
| Adverse | 28 (1.2%) | 2 (2.3%) | 131 (36%) | ||
| Missing (n) | 126 | 7 | 24 | ||
| Chromosomal abnormalities | |||||
| (−5) / del(5q) | 1 (<0.1%) | 0 (0%) | 36 (9.8%) | >.99 | <.001 |
| (−7) | 1 (<0.1%) | 0 (0%) | 32 (8.7%) | >.99 | .002 |
| (+8) | 102 (4.5%) | 3 (3.4%) | 42 (11%) | >.99 | .027 |
| (−17)/17p abnormality | 3 (0.1%) | 1 (1.1%) | 22 (6.0%) | .14 | .10 |
| inv(16) | 0 (0%) | 0 (0%) | 21 (5.7%) | NA | .019 |
| (t8;21) | 0 (0%) | 0 (0%) | 24 (6.6%) | NA | .007 |
| t(9;11) | 0 (0%) | 0 (0%) | 32 (8.8%) | NA | .002 |
| t(v;11) | 1 (<0.1%) | 0 (0%) | 28 (7.7%) | >.99 | .005 |
| Complex | 17 (0.7%) | 2 (2.3%) | 79 (22%) | .15 | <.001 |
| Monosomal | 2 (<0.1%) | 1 (1.1%) | 54 (15%) | .11 | <.001 |
| FLT3-ITD (%) | 998 (42%) | 30 (32%) | 43 (12%) | .043 | <.001 |
| Missing (n) | 40 | 1 | 19 | ||
| FLT3-ITD allelic ratio | .98 | .75 | |||
| Low (<0.5) | 381 (38%) | 13 (43%) | 15 (35%) | ||
| High (≥0.5) | 502 (50%) | 17 (57%) | 23 (53%) | ||
| Missing (n) | 115 (12%) | 0 | 5 (12%) | ||
| ELN 2017 risk group∗ | .46 | <.001 | |||
| Favorable | 1635 (77%) | 70 (79%) | 45 (13%) | ||
| Intermediate | 470 (22%) | 17 (19%) | 163 (46%) | ||
| Adverse | 28 (1.3%) | 2 (2.3%) | 148 (42%) | ||
| Missing(n) | 261 | 7 | 34 | ||
| CR/CRi with chemotherapy | 89% | 80% | 70% | .006 | .001 |
| Refractory disease | 7.2% | 8.7% | 24% | ||
| Death before assessment | 3.8% | 11% | 5.9% | ||
| Day 60 mortality (95% CI) | 5% (4-6) | 15% (7-22) | 11% (8-14) | <.001 | .2 |
| Allogeneic transplant (%) | .19 | .10 | |||
| In first CR/CRi | 536 (22%) | 19 (20%) | 101 (26%) | ||
| At relapse or refractory | 375 (16%) | 10 (10%) | 62 (16%) | ||
| No transplant | 1483 (62%) | 67 (70%) | 227 (58%) | ||
| Number∗ . | De novo (dn) NPM1 AML . | t-NPM1 AML . | t-AML . | P value . | |
|---|---|---|---|---|---|
| 2394 . | 96 . | 390 . | t-NPM1 AML vs dn-NPM1 AML . | t-NPM1 AML vs t-AML . | |
| Age, median (IQR) | 56.00 (47.00-64.00) | 65.00 (58.00-69.25) | 60.00 (52.00-67.00) | <.001 | <.001 |
| Female (%) | 1291 (54%) | 62 (65%) | 251 (64%) | .047 | >.99 |
| Previous therapy | NA | <.001 | |||
| Chemotherapy ± radiotherapy | NA | 55 (57%) | 312 (80%) | ||
| Radiotherapy alone | NA | 41 (43%) | 78 (20%) | ||
| Indication for cytotoxic therapy | NA | .18 | |||
| Hematological | NA | 17 (18%) | 89 (23%) | ||
| Solid tumor | NA | 63 (66%) | 254 (65%) | ||
| Nonmalignant | NA | 9 (9.4%) | 16 (4.1%) | ||
| Unknown | NA | 7 (7.3%) | 31 (7.9%) | ||
| Latency between chemo/radiotherapy and AML, median years (IQR) | NA | 5.00 (3.00-10.00) | 4.00 (2.00-9.00) | NA | .34 |
| Year of diagnosis | .90 | .32 | |||
| Before 2011 | 1300 (54%) | 52 (54%) | 204 (52%) | ||
| 2011-2015 | 706 (29%) | 27 (28%) | 135 (35%) | ||
| After 2015 | 388 (16%) | 17 (18%) | 51 (13%) | ||
| Blood counts at diagnosis | |||||
| WCC, median (IQR) | 28.40 (8.00-70.22) | 31.95 (10.03-63.60) | 4.82 (2.00-22.01) | .67 | <.001 |
| Missing (n) | 22 | 5 | 8 | ||
| Platelets, median (IQR) | 63.00 (37.00-111.00) | 63.00 (36.75-118.50) | 46.50 (25.00-90.00) | .92 | .012 |
| Missing (n) | 38 | 7 | 10 | ||
| BM blast %, median (IQR) | 74.00 (50.00-89.00) | 76.00 (54.50-86.00) | 50.00 (30.75-79.00) | .69 | <.001 |
| Missing (n) | 175 | 9 | 27 | ||
| Karyotype | |||||
| Normal karyotype | 1986 (88%) | 78 (88%) | 103 (28%) | .51 | <.001 |
| Favorable | 0 (0%) | 0 (0%) | 45 (12%) | ||
| Other intermediate | 254 (11%) | 9 (10%) | 87 (24%) | ||
| Adverse | 28 (1.2%) | 2 (2.3%) | 131 (36%) | ||
| Missing (n) | 126 | 7 | 24 | ||
| Chromosomal abnormalities | |||||
| (−5) / del(5q) | 1 (<0.1%) | 0 (0%) | 36 (9.8%) | >.99 | <.001 |
| (−7) | 1 (<0.1%) | 0 (0%) | 32 (8.7%) | >.99 | .002 |
| (+8) | 102 (4.5%) | 3 (3.4%) | 42 (11%) | >.99 | .027 |
| (−17)/17p abnormality | 3 (0.1%) | 1 (1.1%) | 22 (6.0%) | .14 | .10 |
| inv(16) | 0 (0%) | 0 (0%) | 21 (5.7%) | NA | .019 |
| (t8;21) | 0 (0%) | 0 (0%) | 24 (6.6%) | NA | .007 |
| t(9;11) | 0 (0%) | 0 (0%) | 32 (8.8%) | NA | .002 |
| t(v;11) | 1 (<0.1%) | 0 (0%) | 28 (7.7%) | >.99 | .005 |
| Complex | 17 (0.7%) | 2 (2.3%) | 79 (22%) | .15 | <.001 |
| Monosomal | 2 (<0.1%) | 1 (1.1%) | 54 (15%) | .11 | <.001 |
| FLT3-ITD (%) | 998 (42%) | 30 (32%) | 43 (12%) | .043 | <.001 |
| Missing (n) | 40 | 1 | 19 | ||
| FLT3-ITD allelic ratio | .98 | .75 | |||
| Low (<0.5) | 381 (38%) | 13 (43%) | 15 (35%) | ||
| High (≥0.5) | 502 (50%) | 17 (57%) | 23 (53%) | ||
| Missing (n) | 115 (12%) | 0 | 5 (12%) | ||
| ELN 2017 risk group∗ | .46 | <.001 | |||
| Favorable | 1635 (77%) | 70 (79%) | 45 (13%) | ||
| Intermediate | 470 (22%) | 17 (19%) | 163 (46%) | ||
| Adverse | 28 (1.3%) | 2 (2.3%) | 148 (42%) | ||
| Missing(n) | 261 | 7 | 34 | ||
| CR/CRi with chemotherapy | 89% | 80% | 70% | .006 | .001 |
| Refractory disease | 7.2% | 8.7% | 24% | ||
| Death before assessment | 3.8% | 11% | 5.9% | ||
| Day 60 mortality (95% CI) | 5% (4-6) | 15% (7-22) | 11% (8-14) | <.001 | .2 |
| Allogeneic transplant (%) | .19 | .10 | |||
| In first CR/CRi | 536 (22%) | 19 (20%) | 101 (26%) | ||
| At relapse or refractory | 375 (16%) | 10 (10%) | 62 (16%) | ||
| No transplant | 1483 (62%) | 67 (70%) | 227 (58%) | ||
FLT3-ITD, internal tandem duplication of FLT3 as assessed by fragment length analysis; IQR, interquartile range; WCC, white cell count.
For the patients with t-AML (NPM1 wild-type), ELN risk was only assigned where full cytogenetic and mutation data was available. As comutations (beyond FLT3-ITD) do not alter the ELN 2017 risk category for those with an NPM1 mutation, the dn-NPM1 and t-NPM1 groups include patients with complete data for cytogenetics and FLT3-ITD allelic ratio