Clinico-biological and outcome characteristics of adult and pediatric T-ALL cases (GRAALL and FRALLE protocols) according to IKZF1 status
| Characteristic . | No. (%) of patients or median (95% CI) . | . | |||||
|---|---|---|---|---|---|---|---|
| IKZF1Alt . | IKZF1GL . | Total . | P . | ||||
| Total | 26 | (5.5%) | 450 | (94.5%) | 476 | (100%) | |
| Clinical subsets analyzed | |||||||
| Male sex | 21 | (81%) | 339 | (75%) | 360 | (75%) | .6 |
| Age, median (range), y | 23.5 | (1.1-59.1) | 15.2 | (1.2-59) | 15.4 | (1.1-59.1) | .1 |
| Median WBC (range), ×109/L | 74.1 | (2.8-641) | 63.4 | (0.3-980) | 63.8 | (0.3-980) | .3 |
| CNS involvement | 4/26 | (15%) | 47/448 | (11%) | 51/474 | (11%) | .5 |
| ETP classification | 4/16 | (25%) | 51/291 | (18%) | 55/307 | (18%) | .5 |
| TCR status | 17 | 295 | 312 | ||||
| Immature (IM0/δ/γ) | 8 | (47%) | 60 | (20%) | 68 | (22%) | .02* |
| Cortical (IMB, preαβ) | 5 | (29%) | 154 | (52%) | 159 | (51%) | .08 |
| Mature TCRαβ | 3 | (18%) | 42 | (14%) | 45 | (14%) | .7 |
| Mature TCRγδ | 1 | (6%) | 39 | (13%) | 40 | (13%) | .7 |
| Oncogenetics | 24 | 390 | 414 | ||||
| TLX1 | 1 | (4%) | 53 | (14%) | 54 | (13%) | .3 |
| TLX3 | 4 | (17%) | 68 | (17%) | 72 | (17%) | .9 |
| SIL-TAL1 | 2 | (8%) | 55 | (14%) | 57 | (14%) | .6 |
| CALM-AF10 | 1 | (4%) | 12 | (3%) | 13 | (3%) | .5 |
| None of above | 16 | (67%) | 202 | (52%) | 218 | (53%) | .2 |
| HOXA positive | 4/21 | (19%) | 74/315 | (23%) | 78/336 | (24%) | .8 |
| N/F-R/P classifier | 26 | 450 | 476 | ||||
| High-risk classifier | 15 | (58%) | 198 | (44%) | 213 | (45%) | .2 |
| NOTCH1/FBXW7mut | 19 | (73%) | 302 | (67%) | 321 | (67%) | .7 |
| K/N-RASmut | 8 | (31%) | 41 | (9%) | 49 | (10%) | .003* |
| PTENaltered | 2 | (8%) | 80 | (18%) | 82 | (17%) | .3 |
| Treatment response | |||||||
| CR | 24/26 | (92%) | 416/450 | (92%) | 440/476 | (92%) | 1 |
| Prednisone response | 14/26 | (54%) | 245/441 | (56%) | 259/467 | (55%) | 1 |
| MRD1 ≥10−4 | 12/18 | (67%) | 111/322 | (34%) | 123/340 | (36%) | .01* |
| HSCT | 3/24 | (13%) | 93/416 | (22%) | 96/440 | (22%) | .3 |
| Outcome | |||||||
| 5 y CIR (95% CI) | 50% | (32-71) | 28% | (24-32) | 29% | (25-33) | .01* |
| 5 y OS (95% CI) | 37% | (19-55) | 73% | (69-77) | 71% | (67-75) | <.001* |
| Characteristic . | No. (%) of patients or median (95% CI) . | . | |||||
|---|---|---|---|---|---|---|---|
| IKZF1Alt . | IKZF1GL . | Total . | P . | ||||
| Total | 26 | (5.5%) | 450 | (94.5%) | 476 | (100%) | |
| Clinical subsets analyzed | |||||||
| Male sex | 21 | (81%) | 339 | (75%) | 360 | (75%) | .6 |
| Age, median (range), y | 23.5 | (1.1-59.1) | 15.2 | (1.2-59) | 15.4 | (1.1-59.1) | .1 |
| Median WBC (range), ×109/L | 74.1 | (2.8-641) | 63.4 | (0.3-980) | 63.8 | (0.3-980) | .3 |
| CNS involvement | 4/26 | (15%) | 47/448 | (11%) | 51/474 | (11%) | .5 |
| ETP classification | 4/16 | (25%) | 51/291 | (18%) | 55/307 | (18%) | .5 |
| TCR status | 17 | 295 | 312 | ||||
| Immature (IM0/δ/γ) | 8 | (47%) | 60 | (20%) | 68 | (22%) | .02* |
| Cortical (IMB, preαβ) | 5 | (29%) | 154 | (52%) | 159 | (51%) | .08 |
| Mature TCRαβ | 3 | (18%) | 42 | (14%) | 45 | (14%) | .7 |
| Mature TCRγδ | 1 | (6%) | 39 | (13%) | 40 | (13%) | .7 |
| Oncogenetics | 24 | 390 | 414 | ||||
| TLX1 | 1 | (4%) | 53 | (14%) | 54 | (13%) | .3 |
| TLX3 | 4 | (17%) | 68 | (17%) | 72 | (17%) | .9 |
| SIL-TAL1 | 2 | (8%) | 55 | (14%) | 57 | (14%) | .6 |
| CALM-AF10 | 1 | (4%) | 12 | (3%) | 13 | (3%) | .5 |
| None of above | 16 | (67%) | 202 | (52%) | 218 | (53%) | .2 |
| HOXA positive | 4/21 | (19%) | 74/315 | (23%) | 78/336 | (24%) | .8 |
| N/F-R/P classifier | 26 | 450 | 476 | ||||
| High-risk classifier | 15 | (58%) | 198 | (44%) | 213 | (45%) | .2 |
| NOTCH1/FBXW7mut | 19 | (73%) | 302 | (67%) | 321 | (67%) | .7 |
| K/N-RASmut | 8 | (31%) | 41 | (9%) | 49 | (10%) | .003* |
| PTENaltered | 2 | (8%) | 80 | (18%) | 82 | (17%) | .3 |
| Treatment response | |||||||
| CR | 24/26 | (92%) | 416/450 | (92%) | 440/476 | (92%) | 1 |
| Prednisone response | 14/26 | (54%) | 245/441 | (56%) | 259/467 | (55%) | 1 |
| MRD1 ≥10−4 | 12/18 | (67%) | 111/322 | (34%) | 123/340 | (36%) | .01* |
| HSCT | 3/24 | (13%) | 93/416 | (22%) | 96/440 | (22%) | .3 |
| Outcome | |||||||
| 5 y CIR (95% CI) | 50% | (32-71) | 28% | (24-32) | 29% | (25-33) | .01* |
| 5 y OS (95% CI) | 37% | (19-55) | 73% | (69-77) | 71% | (67-75) | <.001* |
| . | Univariate analysis . | Multivariate analysis . | ||||
|---|---|---|---|---|---|---|
| . | SHR . | 95% CI . | P . | SHR . | 95% CI . | P . |
| CIR | ||||||
| Age* | 1.01 | 0.98-1.0 | .57 | — | — | — |
| Log(WBC)* | 1.62 | 1.20-2.18 | .02 | 1.60 | 1.18-2.17 | .003 |
| Prednisone response | 0.67 | 0.47-0.95 | .026 | 0.92 | 0.63-1.34 | .66 |
| 4-gene classifier† | 2.78 | 1.94-3.99 | <.001 | 2.69 | 1.86-3.88 | <.001 |
| IKZF1Alt | 2.12 | 1.17-3.86 | .013 | 2.15 | 1.18-3.91 | .012 |
| OS | ||||||
| Age* | 1.03 | 1.01-1.05 | .001 | 1.04 | 1.02-1.06 | <.001 |
| Log(WBC)* | 1.99 | 1.48-2.67 | <.001 | 2.04 | 1.49-2.79 | <.001 |
| Prednisone response | 0.54 | 0.38-0.76 | <.001 | 0.79 | 0.55-1.15 | .21 |
| 4-gene classifier† | 2.93 | 2.06-4.17 | <.001 | 2.88 | 2.00-4.16 | <.001 |
| IKZF1Alt | 2.94 | 1.74-4.96 | <.001 | 2.80 | 1.61-4.88 | <.001 |
| . | Univariate analysis . | Multivariate analysis . | ||||
|---|---|---|---|---|---|---|
| . | SHR . | 95% CI . | P . | SHR . | 95% CI . | P . |
| CIR | ||||||
| Age* | 1.01 | 0.98-1.0 | .57 | — | — | — |
| Log(WBC)* | 1.62 | 1.20-2.18 | .02 | 1.60 | 1.18-2.17 | .003 |
| Prednisone response | 0.67 | 0.47-0.95 | .026 | 0.92 | 0.63-1.34 | .66 |
| 4-gene classifier† | 2.78 | 1.94-3.99 | <.001 | 2.69 | 1.86-3.88 | <.001 |
| IKZF1Alt | 2.12 | 1.17-3.86 | .013 | 2.15 | 1.18-3.91 | .012 |
| OS | ||||||
| Age* | 1.03 | 1.01-1.05 | .001 | 1.04 | 1.02-1.06 | <.001 |
| Log(WBC)* | 1.99 | 1.48-2.67 | <.001 | 2.04 | 1.49-2.79 | <.001 |
| Prednisone response | 0.54 | 0.38-0.76 | <.001 | 0.79 | 0.55-1.15 | .21 |
| 4-gene classifier† | 2.93 | 2.06-4.17 | <.001 | 2.88 | 2.00-4.16 | <.001 |
| IKZF1Alt | 2.94 | 1.74-4.96 | <.001 | 2.80 | 1.61-4.88 | <.001 |
MRD1 corresponds to MRD evaluation after induction and was performed by allele-specific oligonucleotides polymerase chain reaction. T-cell receptor (TCR) status and oncogenic evaluations were performed as described in the supplemental Methods. CIR, cumulative incidence of relapse; CNS, central nervous system; CR, complete remission; ETP, early thymic precursor; N/F-R/P classifier, NOTCH1/FBXW7-RAS/PTEN classifier (as previously described); HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; SHR, specific hazard ratio; WBC, white blood cell.
Univariate and multivariate analyses of cumulative incidence of relapse and OS: *Continuous variables; †Presence of RAS/PTEN alteration and/or absence of NOTCH1/FBXW7 mutations.