Clinical parameters and mutational status of cohort 1
| Clinical parameters . | Variable . | Total . | TP53 variant . | KRAS variant . | KRAS and TP53 variant . | No TP53 variant . | No KRAS variant . | P value∗ . | P value† . |
|---|---|---|---|---|---|---|---|---|---|
| n (%) . | n (%) . | n (%) . | n (%) . | n (%) . | n (%) . | ||||
| Total | 160 | 5 | 10 | 1 | 154 | 149 | |||
| Sex | Male | 119 (74.4) | 4 (80) | 7 (70) | 1 (100) | 114 (74) | 111 (74.5) | .608 | .897 |
| Female | 41 (25.6) | 1 (20) | 3 (30) | 0 (0) | 40 (26) | 38 (25.5) | |||
| Age at initial diagnosis | Median age (min-max), y | 9.9 (1.0-17.9) | 13.4 (10.2-16.9) | 10.5 (4-16.1) | 13.6 (13.6) | 9.2 (1.0-17.9) | 9.1 (1-17.9) | .031 | .285 |
| Prednisone response | Good | 75 (47.8) | 3 (75) | 4 (44.4) | 0 (0) | 71 (46.7) | 70 (47.6) | .558 | .640 |
| Poor | 83 (52.9) | 1 (25) | 5 (55.6) | 1 (100) | 81 (53.3) | 77 (52.4) | |||
| No data | 3 | 1 | 1 | 0 | 2 | 2 | |||
| MRD1 (day 33)‡ | Low (<10−3) | 48 (36.6) | 2 (66.7) | 0 (0) | 0 (0) | 46 (36.2) | 48 (39.3) | .573 | .018 |
| High (≥10−3) | 83 (63.4) | 1 (33.3) | 8 (100) | 1 (100) | 81 (63.8) | 74 (60.7) | |||
| No data | 29 | 2 | 2 | 0 | 27 | 27 | |||
| MRD2 (day 78)‡ | Low (<10−3) | 95 (72) | 2 (66.7) | 6 (85.7) | 0 (0) | 93 (72.7) | 89 (71.8) | .320 | .844 |
| High (≥10−3) | 37 (28) | 1 (33.3) | 1 (14.3) | 1 (100) | 35 (27.3) | 35 (28.2) | |||
| No data | 28 | 2 | 3 | 0 | 26 | 25 | |||
| Risk stratification | SR | 4 (2.5) | 1 (20) | 0 (0) | 0 (0) | 3 (1.9) | 4 (2.7) | .077 | .850 |
| MR | 60 (37.5) | 2 (40) | 4 (40) | 0 (0) | 58 (37.7) | 56 (37.6) | |||
| HR | 96 (60) | 2 (40) | 6 (60) | 1 (100) | 93 (60.4) | 89 (59.7) | |||
| First-line treatment | SCT | 33 (20.6) | 1 (20) | 2 (20) | 1 (100) | 31 (20.1) | 30 (20.1) | .482 | .852 |
| HR without SCT | 63 (39.4) | 1 (20) | 4 (40) | 0 (0) | 62 (40.3) | 59 (39.6) | |||
| non-HR | 64 (40) | 3 (60) | 4 (40) | 0 (0) | 61 (39.6) | 60 (40.3) |
| Clinical parameters . | Variable . | Total . | TP53 variant . | KRAS variant . | KRAS and TP53 variant . | No TP53 variant . | No KRAS variant . | P value∗ . | P value† . |
|---|---|---|---|---|---|---|---|---|---|
| n (%) . | n (%) . | n (%) . | n (%) . | n (%) . | n (%) . | ||||
| Total | 160 | 5 | 10 | 1 | 154 | 149 | |||
| Sex | Male | 119 (74.4) | 4 (80) | 7 (70) | 1 (100) | 114 (74) | 111 (74.5) | .608 | .897 |
| Female | 41 (25.6) | 1 (20) | 3 (30) | 0 (0) | 40 (26) | 38 (25.5) | |||
| Age at initial diagnosis | Median age (min-max), y | 9.9 (1.0-17.9) | 13.4 (10.2-16.9) | 10.5 (4-16.1) | 13.6 (13.6) | 9.2 (1.0-17.9) | 9.1 (1-17.9) | .031 | .285 |
| Prednisone response | Good | 75 (47.8) | 3 (75) | 4 (44.4) | 0 (0) | 71 (46.7) | 70 (47.6) | .558 | .640 |
| Poor | 83 (52.9) | 1 (25) | 5 (55.6) | 1 (100) | 81 (53.3) | 77 (52.4) | |||
| No data | 3 | 1 | 1 | 0 | 2 | 2 | |||
| MRD1 (day 33)‡ | Low (<10−3) | 48 (36.6) | 2 (66.7) | 0 (0) | 0 (0) | 46 (36.2) | 48 (39.3) | .573 | .018 |
| High (≥10−3) | 83 (63.4) | 1 (33.3) | 8 (100) | 1 (100) | 81 (63.8) | 74 (60.7) | |||
| No data | 29 | 2 | 2 | 0 | 27 | 27 | |||
| MRD2 (day 78)‡ | Low (<10−3) | 95 (72) | 2 (66.7) | 6 (85.7) | 0 (0) | 93 (72.7) | 89 (71.8) | .320 | .844 |
| High (≥10−3) | 37 (28) | 1 (33.3) | 1 (14.3) | 1 (100) | 35 (27.3) | 35 (28.2) | |||
| No data | 28 | 2 | 3 | 0 | 26 | 25 | |||
| Risk stratification | SR | 4 (2.5) | 1 (20) | 0 (0) | 0 (0) | 3 (1.9) | 4 (2.7) | .077 | .850 |
| MR | 60 (37.5) | 2 (40) | 4 (40) | 0 (0) | 58 (37.7) | 56 (37.6) | |||
| HR | 96 (60) | 2 (40) | 6 (60) | 1 (100) | 93 (60.4) | 89 (59.7) | |||
| First-line treatment | SCT | 33 (20.6) | 1 (20) | 2 (20) | 1 (100) | 31 (20.1) | 30 (20.1) | .482 | .852 |
| HR without SCT | 63 (39.4) | 1 (20) | 4 (40) | 0 (0) | 62 (40.3) | 59 (39.6) | |||
| non-HR | 64 (40) | 3 (60) | 4 (40) | 0 (0) | 61 (39.6) | 60 (40.3) |
Analysis of 160 samples of pediatric patients with T-ALL who were treated on ALL-BFM protocols (ALL-BFM 1995, n = 19; ALL-BFM 2000, n = 99; and AIEOP-BFM ALL 2009, n = 42). Samples of initial diagnosis of T-ALL were chosen based on a case-control-design; 81 samples were obtained from patients who later relapsed and 79 from patients who remained in first complete remission for at least 3 years. Patients in CCR were matched to relapsing patients with decreasing priority according to treatment group, MRD after induction and consolidation, prednisone response, blast cell count, sex, and age. Differences in outcome and clinical parameters between different variant groups were assessed by χ2 test for categorical variables and by Mann-Whitney U test for the continuous variable “age.” Statistical significance was defined as P < .05. P values were not adjusted for multiple testing due to the hypothesis-generating concept of our study.
CCR, continuous complete remissions; HR, high risk; max, maximum; min, minimum; MR, medium risk; MRD1/2, minimal residual disease; SCT, stem cell transplantation; SR, standard risk.
P value calculated between all patients with TP53 variants and all patients without TP53 variant.
P value calculated between all patients with KRAS variants and all patients without variants of this gene.
MRD measured at day 33 and day 78 of induction therapy: low level, <10−3 leukemic cells; high level, ≥10−3 leukemic cells in bone marrow aspirate.