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Table 1 Clinico-biological and outcome characteristics of adult and pediatric T-ALL (GRAALL and FRALLE protocols) according to IDH1/2 status

From: Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL

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
  1. p-values < 0.05 are indicated in bold
  2. 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
  3. 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
  4. 1Statistics presented: Median (Minimum–Maximum)
  5. 2Statistical tests performed: Fisher's exact test; Wilcoxon rank-sum test
  6. 3Univariate and multivariate Cox analyses stratified on protocol