Table 1.
Clinico-biological and outcome characteristics of adult and pediatric T-ALL (GRAALL and FRALLE protocols) according to IDH1/2 status
| Variable | IDH2Mut (n = 10) | p value2 | Overall (n = 476) | p value2 | IDH1Mut (n = 5) |
|---|---|---|---|---|---|
| Male | 7/10 (70%) | 0.72 | 357/476 (75%) | 0.34 | 5/5 (100%) |
| Age (y)1 | 47.6 (3.6–59.1) | 0.01 | 15.3 (1.1–59.1) | 0.26 | 21.6 (5.4–56.5) |
| WBC (G/L)1 | 9 (1–400) | 0.01 | 64 (0–980) | 0.60 | 80 (4–110) |
| CNS involvement | 1/10 (10%) | 0.99 | 51/474 (11%) | 0.99 | 0/5 (0%) |
| Immunophenotype | |||||
| ETP phenotype | 3/5 (60%) | 0.04 | 56/307 (18%) | 0.54 | 1/4 (25%) |
| Immature (IM0/δ/γ) | 5/7 (71%) | 0.006 | 89/419 (21%) | 0.99 | 1/5 (20%) |
| Cortical (IMB, preαβ) | 0/7 (0%) | 0.007 | 211/419 (50%) | 0.68 | 2/5 (40%) |
| Mature TCRαβ | 1/7 (14%) | 0.99 | 66/419 (16%) | 0.99 | 0/5 (0%) |
| Mature TCRγδ | 1/7 (14%) | 0.99 | 53/419 (13%) | 0.12 | 2/5 (40%) |
| Oncogenetic classification | |||||
| TLX1 | 0/8 (0%) | 0.60 | 54/415 (13%) | 0.99 | 0/5 (0%) |
| TLX3 | 1/8 (12%) | 0.99 | 72/415 (17%) | 0.21 | 2/5 (40%) |
| SIL-TAL1 | 0/8 (0%) | 0.61 | 57/415 (14%) | 0.99 | 0/5 (0%) |
| CALM-AF10 | 0/8 (0%) | 0.99 | 13/415 (3%) | 0.99 | 0/5 (0%) |
| High-risk classifier | 8/10 (80%) | 0.03 | 209/476 (44%) | 0.99 | 2/5 (40%) |
| Treatment response | |||||
| Rapid prednisone response | 3/10 (30%) | 0.12 | 259/467 (55%) | 0.66 | 2/5 (40%) |
| Complete Remission | 9/10 (90%) | 0.54 | 440/476 (92%) | 0.32 | 4/5 (80%) |
| MRD1 > 10–4 | 1/1 (100%) | 0.36 | 123/340 (36%) | 0.99 | 1/4 (25%) |
| Allo-HSCT | 2/10 (20%) | 0.99 | 101/456 (22%) | 0.99 | 1/5 (20%) |
| Outcome | |||||
| 4-year CIR (95% CI) | 78% (49;97) | < 0.0013 | 29% (25;33) | 0.753 | 25% (4;87) |
| 4-year OS (95% CI) | 30% (7;58) | 0.0013 | 71% (67;75) | 0.613 | 80% (20;97) |
| Univariate and multivariate analysis3 | ||||||
|---|---|---|---|---|---|---|
| Univariate | Multivariate | |||||
| CIR | SHR | 95%CI | p | SHR | 95%CI | p |
| Age | 1.01 | (0.98; 1.03) | 0.57 | - | - | - |
| CNS | 1.57 | (0.85; 2.59) | 0.08 | 1.33 | (0.80; 2.20) | 0.28 |
| Log(WBC) | 1.62 | (1.2; 2.18) | 0.002 | 1.63 | (1.20; 2.22) | 0.002 |
| Prednisone response | 0.67 | (0.47; 0.95) | 0.03 | 1.00 | (0.68; 1.46) | 0.99 |
| High-risk Classifier | 2.78 | (1.94; 3.99) | < 0.001 | 2.62 | (1.81; 3.79) | < 0.001 |
| IDH2Mut | 4.28 | (1.99; 9.23) | < 0.001 | 4.06 | (1.84; 8.96) | 0.001 |
| OS | HR | 95%CI | p | HR | 95%CI | p |
| Age | 1.03 | (1.01; 1.05) | 0.001 | 1.04 | (1.02; 1.07) | < 0.001 |
| CNS | 2.00 | (1.28; 3.14) | 0.002 | 1.67 | (1.02; 1.07) | 0.03 |
| Log(WBC) | 1.99 | (1.48; 2.67) | < 0.001 | 2.00 | (1.46; 2.76) | < 0.001 |
| Prednisone response | 0.54 | (0.38; 0.76) | < 0.001 | 0.85 | (0.59; 1.24) | 0.41 |
| High-risk Classifier | 2.93 | (2.06; 4.17) | < 0.001 | 2.90 | (2.00; 4.19) | < 0.001 |
| IDH2Mut | 3.56 | (1.66; 7.65) | 0.001 | 1.98 | (0.86; 4.57) | 0.11 |
p-values < 0.05 are indicated in bold
MRD1 correspond to MRD evaluation after induction and was performed by allele-specific oligonucleotides polymerase chain reaction. T-cell receptor status and oncogenic were performed as described in supplemental methods. IDH1Mut and IDH2Mut were statistically compared to IDH1WT and IDH2WT patients, respectively
T-ALL: T-cell acute lymphoblastic leukemia; WBC, white blood count; CNS, central nervous system; ETP, early thymic precursor; High Risk classifier, NOTCH1/FBXW7-RAS/PTEN classifier as previously described [3, 4]; CR, complete remission; MRD, minimal residual disease; Allo-HSCT, allogenic hematopoietic stem cell transplantation; CIR, cumulative incidence of relapse; OS, overall survival; HR: hazard ratio, SHR: specific hazard ratio, CI: confidence interval
1Statistics presented: Median (Minimum–Maximum)
2Statistical tests performed: Fisher's exact test; Wilcoxon rank-sum test
3Univariate and multivariate Cox analyses stratified on protocol