Multivariate analysis of factors that influence CR, OS, and RFS, based on study group, individual prognostic variables including key therapeutic steps (study group, allogeneic HSCT), and combined risk classification models (prospective study classification and post hoc ELN 2010 risk stratification)
| . | All patients . | Complete remission . | Overall survival . | Relapse-free survival . | ||||
|---|---|---|---|---|---|---|---|---|
| N . | CR, n (%) . | OR (95% CI) . | P . | Hazard ratio (95% CI) . | P . | Hazard ratio (95% CI) . | P . | |
| Individual prognostic factors | ||||||||
| Study group | ||||||||
| ICE | 286 | 231 (80.8) | 1.00 | 1.00 | 1.00 | |||
| sHD | 286 | 239 (83.6) | 2.11 (1.38-3.23) | .0006 | 0.71 (0.57-0.89) | .004 | 0.70 (0.55-0.89) | .004 |
| HSCT* | ||||||||
| No | 379 | — | — | — | 1.00 | 1.00 | ||
| Yes | 193 | — | — | — | 0.33 (0.25-0.44) | <.0001 | 0.32 (0.23-0.43) | <.0001 |
| Age, y | ||||||||
| ≤45 | 179 | 163 (91.1) | 1.00 | 1.00 | 1.00 | |||
| 45-60 | 253 | 209 (82.6) | 0.65 (0.38-1.11) | .11 | 1.25 (0.93-1.69) | .14 | 0.93 (0.69-1.25) | .62 |
| >60 | 140 | 98 (70.0) | 0.50 (0.28-0.90) | .02 | 1.42 (1.03-1.95) | .03 | 0.81 (0.57-1.16) | .25 |
| Sex | ||||||||
| Male | 301 | 245 (81.4) | 1.09 (0.71-1.68) | .69 | 0.84 (0.67-1.06) | .15 | 0.76 (0.59-0.98) | .04 |
| Female | 271 | 225 (83.0) | 1.00 | 1.00 | 1.00 | |||
| Morphological AML subtype | ||||||||
| SD | 478 | 403 (84.3) | 1.00 | 1.00 | 1.00 | |||
| HR | 94 | 67 (71.3) | 0.62 (0.37-1.06) | .08 | 1.12 (0.83-1.53) | .46 | 1.14 (0.79-1.65) | .49 |
| AML category | ||||||||
| De novo | 494 | 418 (84.6) | 1.00 | 1.00 | 1.00 | |||
| Non de novo | 78 | 52 (66.7) | 0.63 (0.35-1.11) | .10 | 1.39 (1.00-1.92) | .05 | 1.48 (0.99-2.19) | .05 |
| ECOG PS | ||||||||
| 0-1 | 524 | 438 (83.6) | 1.00 | 1.00 | 1.00 | |||
| 2-3 | 48 | 32 (66.7) | 0.48 (0.23-1.02) | .05 | 1.26 (0.85-1.85) | .25 | 0.85 (0.52-1.39) | .53 |
| Hepatosplenomegaly | ||||||||
| No | 487 | 397 (81.5) | 1.00 | 1.00 | 1.00 | |||
| Yes | 85 | 73 (85.9) | 1.49 (0.77-2.88) | .23 | 1.34 (0.97-1.85) | .08 | 1.58 (1.14-2.20) | .006 |
| WBC count, ×109/L | ||||||||
| ≤50 | 443 | 365 (82.4) | 1.00 | 1.00 | 1.00 | |||
| >50 | 129 | 105 (81.4) | 0.60 (0.33-1.07) | .08 | 1.35 (1.01-1.82) | .04 | 1.33 (0.96-1.82) | .08 |
| Cytogenetics | ||||||||
| Favorable | 52 | 50 (96.2) | 1.00 | 1.00 | 1.00 | |||
| Intermediate | 281 | 246 (87.5) | 0.20 (0.05-0.74) | .01 | 2.53 (1.44-4.45) | .001 | 1.91 (1.16-3.14) | .01 |
| Adverse | 170 | 118 (69.4) | 0.10 (0.03-0.36) | .0005 | 5.63 (3.22-9.84) | <.0001 | 4.68 (2.80-7.83) | <.0001 |
| Other | 12 | 11 (91.7) | 0.22 (0.03-1.62) | .13 | 5.46 (2.27-13.15) | .0002 | 3.80 (1.57-9.15) | .003 |
| Genetics | ||||||||
| FLT3-ITD− | 466 | 380 (81.5) | 1.00 | 1.00 | 1.00 | |||
| FLT3-ITD+ | 103 | 88 (85.4) | 0.52 (0.28-0.97) | .03 | 1.90 (1.40-2.57) | <.0001 | 1.88 (1.36-2.62) | .0002 |
| NPM1 wild-type | 384 | 299 (77.9) | 1.00 | 1.00 | 1.00 | |||
| NPM1 mutated | 167 | 152 (91.0) | 4.52 (2.40-8.55) | <.0001 | 0.56 (0.42-0.76) | .0001 | 0.64 (0.47-0.86) | .003 |
| Risk stratification models | ||||||||
| Study risk classification† | ||||||||
| SR | 156 | 145 (92.9) | 1.00 | 1.00 | 1.00 | |||
| HR | 416 | 325 (78.1) | 0.31 (0.18-0.55) | <.0001 | 3.52 (2.58-4.80) | <.0001 | 3.22 (2.37-4.38) | <.0001 |
| ELN 2010 risk stratification‡ | ||||||||
| Favorable | 166 | 159 (95.8) | 1.00 | 1.00 | 1.00 | |||
| Intermediate 1 | 147 | 119 (81.0) | 0.18 (0.09-0.39) | <.0001 | 3.55 (2.46-5.11) | <.0001 | 2.78 (1.95-3.95) | <.0001 |
| Intermediate 2 | 70 | 58 (82.9) | 0.21 (0.09-0.52) | .0006 | 3.81 (2.46-5.90) | <.0001 | 4.53 (2.95-6.96) | <.0001 |
| Adverse | 135 | 92 (68.1) | 0.11 (0.05-0.24) | <.0001 | 6.88 (4.73-9.99) | <.0001 | 5.69 (3.89-8.33) | <.0001 |
| . | All patients . | Complete remission . | Overall survival . | Relapse-free survival . | ||||
|---|---|---|---|---|---|---|---|---|
| N . | CR, n (%) . | OR (95% CI) . | P . | Hazard ratio (95% CI) . | P . | Hazard ratio (95% CI) . | P . | |
| Individual prognostic factors | ||||||||
| Study group | ||||||||
| ICE | 286 | 231 (80.8) | 1.00 | 1.00 | 1.00 | |||
| sHD | 286 | 239 (83.6) | 2.11 (1.38-3.23) | .0006 | 0.71 (0.57-0.89) | .004 | 0.70 (0.55-0.89) | .004 |
| HSCT* | ||||||||
| No | 379 | — | — | — | 1.00 | 1.00 | ||
| Yes | 193 | — | — | — | 0.33 (0.25-0.44) | <.0001 | 0.32 (0.23-0.43) | <.0001 |
| Age, y | ||||||||
| ≤45 | 179 | 163 (91.1) | 1.00 | 1.00 | 1.00 | |||
| 45-60 | 253 | 209 (82.6) | 0.65 (0.38-1.11) | .11 | 1.25 (0.93-1.69) | .14 | 0.93 (0.69-1.25) | .62 |
| >60 | 140 | 98 (70.0) | 0.50 (0.28-0.90) | .02 | 1.42 (1.03-1.95) | .03 | 0.81 (0.57-1.16) | .25 |
| Sex | ||||||||
| Male | 301 | 245 (81.4) | 1.09 (0.71-1.68) | .69 | 0.84 (0.67-1.06) | .15 | 0.76 (0.59-0.98) | .04 |
| Female | 271 | 225 (83.0) | 1.00 | 1.00 | 1.00 | |||
| Morphological AML subtype | ||||||||
| SD | 478 | 403 (84.3) | 1.00 | 1.00 | 1.00 | |||
| HR | 94 | 67 (71.3) | 0.62 (0.37-1.06) | .08 | 1.12 (0.83-1.53) | .46 | 1.14 (0.79-1.65) | .49 |
| AML category | ||||||||
| De novo | 494 | 418 (84.6) | 1.00 | 1.00 | 1.00 | |||
| Non de novo | 78 | 52 (66.7) | 0.63 (0.35-1.11) | .10 | 1.39 (1.00-1.92) | .05 | 1.48 (0.99-2.19) | .05 |
| ECOG PS | ||||||||
| 0-1 | 524 | 438 (83.6) | 1.00 | 1.00 | 1.00 | |||
| 2-3 | 48 | 32 (66.7) | 0.48 (0.23-1.02) | .05 | 1.26 (0.85-1.85) | .25 | 0.85 (0.52-1.39) | .53 |
| Hepatosplenomegaly | ||||||||
| No | 487 | 397 (81.5) | 1.00 | 1.00 | 1.00 | |||
| Yes | 85 | 73 (85.9) | 1.49 (0.77-2.88) | .23 | 1.34 (0.97-1.85) | .08 | 1.58 (1.14-2.20) | .006 |
| WBC count, ×109/L | ||||||||
| ≤50 | 443 | 365 (82.4) | 1.00 | 1.00 | 1.00 | |||
| >50 | 129 | 105 (81.4) | 0.60 (0.33-1.07) | .08 | 1.35 (1.01-1.82) | .04 | 1.33 (0.96-1.82) | .08 |
| Cytogenetics | ||||||||
| Favorable | 52 | 50 (96.2) | 1.00 | 1.00 | 1.00 | |||
| Intermediate | 281 | 246 (87.5) | 0.20 (0.05-0.74) | .01 | 2.53 (1.44-4.45) | .001 | 1.91 (1.16-3.14) | .01 |
| Adverse | 170 | 118 (69.4) | 0.10 (0.03-0.36) | .0005 | 5.63 (3.22-9.84) | <.0001 | 4.68 (2.80-7.83) | <.0001 |
| Other | 12 | 11 (91.7) | 0.22 (0.03-1.62) | .13 | 5.46 (2.27-13.15) | .0002 | 3.80 (1.57-9.15) | .003 |
| Genetics | ||||||||
| FLT3-ITD− | 466 | 380 (81.5) | 1.00 | 1.00 | 1.00 | |||
| FLT3-ITD+ | 103 | 88 (85.4) | 0.52 (0.28-0.97) | .03 | 1.90 (1.40-2.57) | <.0001 | 1.88 (1.36-2.62) | .0002 |
| NPM1 wild-type | 384 | 299 (77.9) | 1.00 | 1.00 | 1.00 | |||
| NPM1 mutated | 167 | 152 (91.0) | 4.52 (2.40-8.55) | <.0001 | 0.56 (0.42-0.76) | .0001 | 0.64 (0.47-0.86) | .003 |
| Risk stratification models | ||||||||
| Study risk classification† | ||||||||
| SR | 156 | 145 (92.9) | 1.00 | 1.00 | 1.00 | |||
| HR | 416 | 325 (78.1) | 0.31 (0.18-0.55) | <.0001 | 3.52 (2.58-4.80) | <.0001 | 3.22 (2.37-4.38) | <.0001 |
| ELN 2010 risk stratification‡ | ||||||||
| Favorable | 166 | 159 (95.8) | 1.00 | 1.00 | 1.00 | |||
| Intermediate 1 | 147 | 119 (81.0) | 0.18 (0.09-0.39) | <.0001 | 3.55 (2.46-5.11) | <.0001 | 2.78 (1.95-3.95) | <.0001 |
| Intermediate 2 | 70 | 58 (82.9) | 0.21 (0.09-0.52) | .0006 | 3.81 (2.46-5.90) | <.0001 | 4.53 (2.95-6.96) | <.0001 |
| Adverse | 135 | 92 (68.1) | 0.11 (0.05-0.24) | <.0001 | 6.88 (4.73-9.99) | <.0001 | 5.69 (3.89-8.33) | <.0001 |
Variations in the prognostic significance of individual risk factors outside the combined risk models are reported in the footnotes
OR, odds ratio.
Time-dependent variable.
The study risk classification incorporated: morphological AML subtype, AML category, hepatosplenomegaly, WBC, FLT3 mutations, and cytogenetics. In addition to SR risk class, the modified prognostic model identified significant associations for improved CR (sHD group, P = .0008; age ≤60 years, P = .01; mutated NPM1, P < .0001), OS (HSCT, P < .0001; sHD group, P = .05; mutated NPM1, P = .0006), and RFS (HSCT, P < .0001; sHD group, P = .003; mutated NPM1, P = .007). All other factors did not reach statistical significance (P > .05).
The ELN 2010 risk stratification incorporated: cytogenetics and genetics. In addition to the favorable risk class, the modified prognostic model identified significant associations for improved CR (sHD group, P = .0004; age ≤ 60 years, P = .03), OS (HSCT, P < .0001; sHD group, P = .003; no hepatosplenomegaly, P = .009; WBC, ≤50 ×109/L, P = .02), and RFS (HSCT, P < .0001; sHD group, P = .001; no hepatosplenomegaly, P = .0002; WBC, ≤50 ×109/L, P = .02). All other factors did not reach statistical significance (P > .05).