Demographic characteristics of the CIMP-low and CIMP-high classes in CIMP-classified pediatric patients with T-ALL in the study NOPHO ALL2008 cohort and the DCOG ALL-10/ALL-11 validation cohorts
| . | NOPHO ALL2008 T-ALL cohort (n = 192) . | . | DCOG ALL-10/ALL-11 T-ALL cohort (n = 156) . | ||||
|---|---|---|---|---|---|---|---|
| CIMP low (n = 76, 39.6%) . | CIMP high (n = 116, 60.4%) . | P value . | CIMP low (n = 60, 38.5%) . | CIMP high (n = 96, 61.5%) . | P value . | ||
| Age, y | 7 (1-17) | 7 (1-17) | .573 | Age, y | 8 (1-17) | 8 (1-17) | .335 |
| Male/female | 58 (76.3%)/18 (23.7%) | 86 (74.1%)/30 (25.9%) | .890 | Male/female | 42 (70.0%)/18 (30.0%) | 69 (71.9%)/27 (28.1%) | .857 |
| WBC × 109/L | 173.0 (1.5-983) | 67.7 (1.2-825) | <.001∗∗∗ | WBC × 109/L | 118.7 (3.8-663) | 51.4 (1.0-954) | <.001∗∗∗ |
| CNS status (CNS1-2/CNS3/NA) | 68 (89.5%)/7 (9.2%)/1 (1.3%) | 98 (84.5%)/18 (15.5%)/0 (0%) | .274 | CNS status ([CNS1-CNS2-TLPneg-TLPpos]/CNS3/NA) | 51 (85%)/2 (3.3%)/7 (11.7%) | 81 (84.4%)/9 (9.4%)/6 (6.3%) | .213 |
| ETP-ALL (non-ETP/ETP/NA) | 54 (71.1%)/3 (3.9%)/19 (25%) | 68 (58.6%)/9 (7.8%)/39 (33.6%) | .236 | — | — | — | — |
| Deceased/alive | 20 (26.3%)/56 (73.7%) | 11 (9.5%)/105 (90.5%) | .003∗∗ | Deceased/alive | 18 (30.0%)/42 (70.0%) | 13 (13.5%)/83 (86.5%) | .014∗ |
| Relapse | 18 (23.7%) | 6 (5.2%) | <.001∗∗∗ | Relapse | 13 (21.7%) | 7 (7.3%) | .013∗ |
| CR | 50 (65.8%) | 102 (87.9%) | <.001∗∗∗ | CR | 39 (65%) | 81 (84.4%) | .006∗∗ |
| DCR | 5 (6.6%) | 7 (6.0%) | 1.000 | DCR | 4 (6.7%) | 4 (4.2%) | .485 |
| IF | 1 (1.3%) | 1 (0.9%) | 1.000 | Nonresponder | 2 (3.3%) | 1 (1%) | .559 |
| SMN | 2 (2.6%) | 0 (0.0%) | .155 | SMN | 1 (1.7%) | 1 (1%) | 1.000 |
| — | — | — | — | Early death | 1 (1.7%) | 2 (2.1%) | 1.000 |
| pCIR5yr, % (95% CI) | 18% (11-28) | 5.3% (2.2-10) | <.001∗∗∗ | pCIR5yr, % (95% CI) | 25% (14-37) | 7.8% (3.4-15) | .007∗∗ |
| pEFS5yr, % (95% CI) | 72.3% (62.9-83.1) | 88.6% (82.9-94.6) | <.001∗∗∗ | pEFS5yr, % (95% CI) | 65.0% (54.0-78.3) | 84.4% (77.4-92.0) | .006∗∗ |
| pOS5yr, % (95% CI) | 74.4% (65.0-85.1) | 91.1% (86.0-96.5) | .002∗∗ | pOS5yr, % (95% CI) | 71.7% (61.1-84.0) | 86.5% (79.9-93.6) | .015∗ |
| D15MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 10 (13.2%)/10 (13.2%)/37 (48.7%)/11 (14.5%)/7 (9.2%)/1 (1.3%) | 28 (24.1%)/18 (15.5%)/34 (29.3%)/15 (12.9%)/17 (14.7%)/4 (3.4%) | .070 | — | — | — | — |
| D29MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 22 (28.9%)/13 (17.1%)/32 (42.1%)/3 (3.9%)/3 (3.9%)/3 (3.9%) | 38 (32.8%)/19 (16.4%)/39 (33.6%)/4 (3.4%)/0 (0%)/16 (13.8%) | .308 | D33MRD <0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 18 (30%)/9 (15%)/16 (26.7%)/6 (10%)/4 (6.7%)/7 (11.7%) | 47 (49%)/11 (11.5%)/17 (17.7%)/6 (6.3%)/3 (3.1%)/12 (12.5%) | .137 |
| D79MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 31 (40.8%)/6 (7.9%)/1 (1.3%)/0 (0%)/0 (0%)/38 (50%) | 56 (48.3%)/7 (6%)/0 (0%)/ 0 (0%)/0 (0%)/53 (45.7%) | .349 | D79MRD <0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 39 (65%)/3 (5%)/2 (3.3%)/6 (10%)/1 (1.7%)/9 (15%) | 69 (71.9%)/8 (8.3%)/1 (1%)/0 (0%)/1 (1%)/17 (17.7%) | .019∗ |
| Final risk stratification (IR/HR/NS) | 34 (44.7%)/41 (54.0%)/1 (1.3%) | 58 (50.0%)/57 (49.1%)/1 (0.9%) | .553 | Final risk stratification (SR/MR/HR/DI) | 2 (3.3%)/39 (65%)/16 (26.7%)/3 (5%) | 15 (15.6%)/62 (64.6%)/16 (16.7%)/3 (3.1%) | .049∗ |
| Final risk stratification (IR/HR-chemotherapy/HR-SCT/IF) | 34 (44.7%)/36 (47.4%)/5 (6.6%)/1 (1.3%) | 58 (50.0%)/45 (38.8%)/12 (10.3%)/1 (0.9%) | .577 | Final risk stratification (SR/MR/HR + SCT/HR without SCT/HR with SCT intention/DI) | 2 (3.3%)/39 (65%)/16 (26.7%)/0 (0%)/0 (0%)/ 3 (5.0%) | 15 (15.6%)/62 (64.6%)/12 (12.5%)/1 (1.0%)/3 (3.1%)/3 (3.1%) | .018∗ |
| CRs final risk stratification (IR/HR) | 26 (52.0%)/24 (48.0%) | 56 (54.9%)/46 (45.1%) | .863 | CRs final risk stratification (SR/MR/HR) | 1 (2.6%)/31 (79.5%)/7 (17.9%) | 14 (17.3%)/59 (72.8%)/8 (9.9%) | .036∗ |
| . | NOPHO ALL2008 T-ALL cohort (n = 192) . | . | DCOG ALL-10/ALL-11 T-ALL cohort (n = 156) . | ||||
|---|---|---|---|---|---|---|---|
| CIMP low (n = 76, 39.6%) . | CIMP high (n = 116, 60.4%) . | P value . | CIMP low (n = 60, 38.5%) . | CIMP high (n = 96, 61.5%) . | P value . | ||
| Age, y | 7 (1-17) | 7 (1-17) | .573 | Age, y | 8 (1-17) | 8 (1-17) | .335 |
| Male/female | 58 (76.3%)/18 (23.7%) | 86 (74.1%)/30 (25.9%) | .890 | Male/female | 42 (70.0%)/18 (30.0%) | 69 (71.9%)/27 (28.1%) | .857 |
| WBC × 109/L | 173.0 (1.5-983) | 67.7 (1.2-825) | <.001∗∗∗ | WBC × 109/L | 118.7 (3.8-663) | 51.4 (1.0-954) | <.001∗∗∗ |
| CNS status (CNS1-2/CNS3/NA) | 68 (89.5%)/7 (9.2%)/1 (1.3%) | 98 (84.5%)/18 (15.5%)/0 (0%) | .274 | CNS status ([CNS1-CNS2-TLPneg-TLPpos]/CNS3/NA) | 51 (85%)/2 (3.3%)/7 (11.7%) | 81 (84.4%)/9 (9.4%)/6 (6.3%) | .213 |
| ETP-ALL (non-ETP/ETP/NA) | 54 (71.1%)/3 (3.9%)/19 (25%) | 68 (58.6%)/9 (7.8%)/39 (33.6%) | .236 | — | — | — | — |
| Deceased/alive | 20 (26.3%)/56 (73.7%) | 11 (9.5%)/105 (90.5%) | .003∗∗ | Deceased/alive | 18 (30.0%)/42 (70.0%) | 13 (13.5%)/83 (86.5%) | .014∗ |
| Relapse | 18 (23.7%) | 6 (5.2%) | <.001∗∗∗ | Relapse | 13 (21.7%) | 7 (7.3%) | .013∗ |
| CR | 50 (65.8%) | 102 (87.9%) | <.001∗∗∗ | CR | 39 (65%) | 81 (84.4%) | .006∗∗ |
| DCR | 5 (6.6%) | 7 (6.0%) | 1.000 | DCR | 4 (6.7%) | 4 (4.2%) | .485 |
| IF | 1 (1.3%) | 1 (0.9%) | 1.000 | Nonresponder | 2 (3.3%) | 1 (1%) | .559 |
| SMN | 2 (2.6%) | 0 (0.0%) | .155 | SMN | 1 (1.7%) | 1 (1%) | 1.000 |
| — | — | — | — | Early death | 1 (1.7%) | 2 (2.1%) | 1.000 |
| pCIR5yr, % (95% CI) | 18% (11-28) | 5.3% (2.2-10) | <.001∗∗∗ | pCIR5yr, % (95% CI) | 25% (14-37) | 7.8% (3.4-15) | .007∗∗ |
| pEFS5yr, % (95% CI) | 72.3% (62.9-83.1) | 88.6% (82.9-94.6) | <.001∗∗∗ | pEFS5yr, % (95% CI) | 65.0% (54.0-78.3) | 84.4% (77.4-92.0) | .006∗∗ |
| pOS5yr, % (95% CI) | 74.4% (65.0-85.1) | 91.1% (86.0-96.5) | .002∗∗ | pOS5yr, % (95% CI) | 71.7% (61.1-84.0) | 86.5% (79.9-93.6) | .015∗ |
| D15MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 10 (13.2%)/10 (13.2%)/37 (48.7%)/11 (14.5%)/7 (9.2%)/1 (1.3%) | 28 (24.1%)/18 (15.5%)/34 (29.3%)/15 (12.9%)/17 (14.7%)/4 (3.4%) | .070 | — | — | — | — |
| D29MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 22 (28.9%)/13 (17.1%)/32 (42.1%)/3 (3.9%)/3 (3.9%)/3 (3.9%) | 38 (32.8%)/19 (16.4%)/39 (33.6%)/4 (3.4%)/0 (0%)/16 (13.8%) | .308 | D33MRD <0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 18 (30%)/9 (15%)/16 (26.7%)/6 (10%)/4 (6.7%)/7 (11.7%) | 47 (49%)/11 (11.5%)/17 (17.7%)/6 (6.3%)/3 (3.1%)/12 (12.5%) | .137 |
| D79MRD < 0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 31 (40.8%)/6 (7.9%)/1 (1.3%)/0 (0%)/0 (0%)/38 (50%) | 56 (48.3%)/7 (6%)/0 (0%)/ 0 (0%)/0 (0%)/53 (45.7%) | .349 | D79MRD <0.01/0.01-0.1/0.1-5/5-25/≥25/NA | 39 (65%)/3 (5%)/2 (3.3%)/6 (10%)/1 (1.7%)/9 (15%) | 69 (71.9%)/8 (8.3%)/1 (1%)/0 (0%)/1 (1%)/17 (17.7%) | .019∗ |
| Final risk stratification (IR/HR/NS) | 34 (44.7%)/41 (54.0%)/1 (1.3%) | 58 (50.0%)/57 (49.1%)/1 (0.9%) | .553 | Final risk stratification (SR/MR/HR/DI) | 2 (3.3%)/39 (65%)/16 (26.7%)/3 (5%) | 15 (15.6%)/62 (64.6%)/16 (16.7%)/3 (3.1%) | .049∗ |
| Final risk stratification (IR/HR-chemotherapy/HR-SCT/IF) | 34 (44.7%)/36 (47.4%)/5 (6.6%)/1 (1.3%) | 58 (50.0%)/45 (38.8%)/12 (10.3%)/1 (0.9%) | .577 | Final risk stratification (SR/MR/HR + SCT/HR without SCT/HR with SCT intention/DI) | 2 (3.3%)/39 (65%)/16 (26.7%)/0 (0%)/0 (0%)/ 3 (5.0%) | 15 (15.6%)/62 (64.6%)/12 (12.5%)/1 (1.0%)/3 (3.1%)/3 (3.1%) | .018∗ |
| CRs final risk stratification (IR/HR) | 26 (52.0%)/24 (48.0%) | 56 (54.9%)/46 (45.1%) | .863 | CRs final risk stratification (SR/MR/HR) | 1 (2.6%)/31 (79.5%)/7 (17.9%) | 14 (17.3%)/59 (72.8%)/8 (9.9%) | .036∗ |
Categorical variables are presented as number (%) and compared by the Fisher exact test. Continuous variables are presented as median (min-max) and compared by the Mann-Whitney U test. Five-year cumulative incidence of release (pCIR5yr) probability was estimated accounting for competing events by the Fine-Gray test, and EFS (pEFS5yr) and OS (pOS5yr) are presented as probabilities (95% CI) and compared by the log-rank test.
CI, confidence interval; DI, death in induction; NS, not stratified due to induction failure, thus not included in the Fisher exact test; NA, not available; TLP, traumatic lumbar puncture. ∗P < .05, ∗∗P < .01, ∗∗∗ P < .001.