Clinicobiological and outcome characteristics of adult and pediatric T-ALL (GRAALL and FRALLE protocols) according to TP53 status
| Variable . | TP53Alt . | TP53WT . | Total . | P value∗ . |
|---|---|---|---|---|
| n = 21 (4%) . | n = 455 (96%) . | N = 476 . | ||
| Male (%) | 14/21 (67) | 343/455 (75) | 357/476 (75) | .4 |
| Age, y† | 23.4 (4.0-51.8) | 15.3 (1.1-59.1) | 15.3 (1.1-59.1) | .5 |
| WBC, g/L† | 25 (5-674) | 66 (0-980) | 64 (0-980) | .01 |
| CNS involvement (%)‡ | 3/21 (14) | 48/453 (11) | 51/474 (11) | .5 |
| Immunophenotype (%) | ||||
| Early thymic precursor phenotype | 6/16 (38) | 50/291 (17) | 56/307 (18) | .09 |
| Immature (IM0/δ/γ)§ | 8/20 (40) | 81/399 (20) | 89/419 (21) | .048 |
| αβ lineage | 6/20 (30) | 205/399 (51) | 211/419 (50) | .07 |
| Mature TCRγδ | 3/20 (15) | 63/399 (16) | 66/419 (16) | >.9 |
| Oncogenetic classification (%) | ||||
| TLX1 | 1/18 (6) | 53/397 (13) | 54/415 (13) | .5 |
| TLX3 | 2/18 (11) | 70/397 (18) | 72/415 (17) | .8 |
| SIL-TAL1 | 1/18 (6) | 56/397 (14) | 57/415 (14) | .5 |
| CALM-AF10 | 0/18 (0) | 13/397 (3) | 13/415 (3) | >.9 |
| High-risk classifier|| | 13/21 (62) | 196/455 (43) | 209/476 (44) | .12 |
| Treatment response (%) | ||||
| Prednisone response | 13/21 (62) | 246/446 (55) | 259/467 (55) | .7 |
| Chemosensitivity | 12/21 (57) | 325/446 (73) | 337/467 (72) | .1 |
| MRD1 >10−4 | 9/12 (75) | 114/328 (35) | 123/340 (36) | .01 |
| Complete remission | 17/21 (81) | 423/455 (93) | 440/476 (92) | .07 |
| Allo-HSCT | 4/20 (20) | 97/436 (22) | 101/456 (22) | .7 |
| Outcome, % | ||||
| 5-y CIR (95% CI) | 65 (11-43) | 27 (23-32) | 29 (25-33) | <.001 |
| 5-y OS (95% CI) | 48 (26-67) | 72 (68-76) | 71 (67-75) | .005 |
| Variable . | TP53Alt . | TP53WT . | Total . | P value∗ . |
|---|---|---|---|---|
| n = 21 (4%) . | n = 455 (96%) . | N = 476 . | ||
| Male (%) | 14/21 (67) | 343/455 (75) | 357/476 (75) | .4 |
| Age, y† | 23.4 (4.0-51.8) | 15.3 (1.1-59.1) | 15.3 (1.1-59.1) | .5 |
| WBC, g/L† | 25 (5-674) | 66 (0-980) | 64 (0-980) | .01 |
| CNS involvement (%)‡ | 3/21 (14) | 48/453 (11) | 51/474 (11) | .5 |
| Immunophenotype (%) | ||||
| Early thymic precursor phenotype | 6/16 (38) | 50/291 (17) | 56/307 (18) | .09 |
| Immature (IM0/δ/γ)§ | 8/20 (40) | 81/399 (20) | 89/419 (21) | .048 |
| αβ lineage | 6/20 (30) | 205/399 (51) | 211/419 (50) | .07 |
| Mature TCRγδ | 3/20 (15) | 63/399 (16) | 66/419 (16) | >.9 |
| Oncogenetic classification (%) | ||||
| TLX1 | 1/18 (6) | 53/397 (13) | 54/415 (13) | .5 |
| TLX3 | 2/18 (11) | 70/397 (18) | 72/415 (17) | .8 |
| SIL-TAL1 | 1/18 (6) | 56/397 (14) | 57/415 (14) | .5 |
| CALM-AF10 | 0/18 (0) | 13/397 (3) | 13/415 (3) | >.9 |
| High-risk classifier|| | 13/21 (62) | 196/455 (43) | 209/476 (44) | .12 |
| Treatment response (%) | ||||
| Prednisone response | 13/21 (62) | 246/446 (55) | 259/467 (55) | .7 |
| Chemosensitivity | 12/21 (57) | 325/446 (73) | 337/467 (72) | .1 |
| MRD1 >10−4 | 9/12 (75) | 114/328 (35) | 123/340 (36) | .01 |
| Complete remission | 17/21 (81) | 423/455 (93) | 440/476 (92) | .07 |
| Allo-HSCT | 4/20 (20) | 97/436 (22) | 101/456 (22) | .7 |
| Outcome, % | ||||
| 5-y CIR (95% CI) | 65 (11-43) | 27 (23-32) | 29 (25-33) | <.001 |
| 5-y OS (95% CI) | 48 (26-67) | 72 (68-76) | 71 (67-75) | .005 |
| . | Univariate and multivariate analysis¶ . | |||||
|---|---|---|---|---|---|---|
| Univariate . | Multivariate . | |||||
| Specific HR . | 95% CI . | P value . | Specific HR . | 95% CI . | P value . | |
| CIR | ||||||
| Age, y | 1.01 | 0.98-1.03 | .57 | — | — | — |
| CNS | 1.57 | 0.85-2.59 | .08 | 1.28 | 0.77-2.13 | .34 |
| Log (WBC) | 1.62 | 1.2-2.18 | .002 | 1.62 | 1.19-2.19 | .002 |
| Prednisone response | 0.67 | 0.47-0.95 | .03 | 0.93 | 0.64-1.35 | .70 |
| High-risk classifier§ | 2.78 | 1.94-3.99 | <.001 | 2.58 | 1.78-3.74 | <.001 |
| TP53Alt | 3.11 | 1.67-5.78 | <.001 | 2.90 | 1.55-5.44 | .001 |
| . | Univariate and multivariate analysis¶ . | |||||
|---|---|---|---|---|---|---|
| Univariate . | Multivariate . | |||||
| Specific HR . | 95% CI . | P value . | Specific HR . | 95% CI . | P value . | |
| CIR | ||||||
| Age, y | 1.01 | 0.98-1.03 | .57 | — | — | — |
| CNS | 1.57 | 0.85-2.59 | .08 | 1.28 | 0.77-2.13 | .34 |
| Log (WBC) | 1.62 | 1.2-2.18 | .002 | 1.62 | 1.19-2.19 | .002 |
| Prednisone response | 0.67 | 0.47-0.95 | .03 | 0.93 | 0.64-1.35 | .70 |
| High-risk classifier§ | 2.78 | 1.94-3.99 | <.001 | 2.58 | 1.78-3.74 | <.001 |
| TP53Alt | 3.11 | 1.67-5.78 | <.001 | 2.90 | 1.55-5.44 | .001 |
| . | Univariate and multivariate analysis¶ . | |||||
|---|---|---|---|---|---|---|
| Univariate . | Multivariate . | |||||
| HR . | 95% CI . | P value . | HR . | 95% CI . | P value . | |
| OS | ||||||
| Age | 1.03 | 1.01-1.05 | .001 | 1.05 | 1.03-1.07 | <.001 |
| CNS | 2.00 | 1.28-3.14 | .002 | 1.64 | 1.02-2.64 | .04 |
| Log (WBC) | 1.99 | 1.48-2.67 | <.001 | 2.01 | 1.51-2.86 | <.001 |
| Prednisone response | 0.54 | 0.38-0.76 | <.001 | 0.83 | 0.57-1.20 | .31 |
| High-risk classifier | 2.93 | 2.06-4.17 | <.001 | 2.90 | 2.01-4.18 | <.001 |
| TP53Alt | 2.34 | 1.30-4.24 | .005 | 2.87 | 1.56-5.26 | .001 |
| . | Univariate and multivariate analysis¶ . | |||||
|---|---|---|---|---|---|---|
| Univariate . | Multivariate . | |||||
| HR . | 95% CI . | P value . | HR . | 95% CI . | P value . | |
| OS | ||||||
| Age | 1.03 | 1.01-1.05 | .001 | 1.05 | 1.03-1.07 | <.001 |
| CNS | 2.00 | 1.28-3.14 | .002 | 1.64 | 1.02-2.64 | .04 |
| Log (WBC) | 1.99 | 1.48-2.67 | <.001 | 2.01 | 1.51-2.86 | <.001 |
| Prednisone response | 0.54 | 0.38-0.76 | <.001 | 0.83 | 0.57-1.20 | .31 |
| High-risk classifier | 2.93 | 2.06-4.17 | <.001 | 2.90 | 2.01-4.18 | <.001 |
| TP53Alt | 2.34 | 1.30-4.24 | .005 | 2.87 | 1.56-5.26 | .001 |
MRD1 correspond to MRD evaluation after induction and was performed by allele-specific oligonucleotides polymerase chain reaction. TCR status and oncogenic were performed as described in supplemental Methods.
P < .05 are indicated in bold.
allo-HSCT, allogeneic hematopoietic stem cell transplantation; CNS, central nervous system; WBC, white blood count.
Statistical tests performed: Fisher exact test and Wilcoxon rank-sum test.
Statistics presented: median (minimum-maximum).
CNS involvement: CNS3 in FRALLE2000 trial, CNS2 and/or CNS3 in GRAALL2003 and GRAALL2005 trial.
T-ALL are divided into 3 subclasses as following: (1) immature (no detectable TCRβ variable diversity joining): IM0 (TCRδ and TCRγ germ line), IMδ (TCRδ rearranged but not TCRγ), and IMg (both TCRδ and TCRγ rearranged); (2) T-ALL with TCRαβ lineage (including both early-cortical IMb/pre-αβ and mature sTCRαβ+); and (3) mature sTCRγδ.12
Low-risk classifier: NOTCH1 and/or FBXW7 (N/F) mutation without N/K-RAS and PTEN (R/P) alteration. High-risk classifier: N/F mutation with R/P alteration, N/F WT with or without R/P alteration.10,16
Univariate and multivariate Cox analyses stratified on protocol.