Cumulative risk of isolated or any CNS relapse according to selected clinical and biological characteristics among patients with B-ALL or T-ALL
| . | Univariate analysis . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable . | Patients with B-ALL . | Patients with T-ALL . | ||||||||||||
| No. total . | No. of isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, % (95% CI) . | P . | No. of any CNS relapse . | 5-y cumulative risk of any CNS relapse, % (95% CI) . | P . | No. total . | No. of isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, % (95% CI) . | P . | No. of any CNS relapse . | 5-y cumulative risk of any CNS relapse, % (95% CI) . | P . | |
| Intrathecal therapy with total intravenous anesthesia | .01 | .01 | .99 | .77 | ||||||||||
| No | 6120 | 77 | 1.8 (1.4-2.2) | 98 | 2.6 (2.0-3.2) | 649 | 26 | 4.6 (2.8-6.4) | 31 | 5.8 (3.8-7.8) | ||||
| Yes | 796 | 2 | 0.4 (0-1.1) | 4 | 1.1 (0-2.2) | 75 | 3 | 4.7 (0-10.0) | 3 | 4.7 (0-10.0) | ||||
| First CSF examination | .006 | .05 | .77 | .87 | ||||||||||
| Conventional cytology | 5911 | 76 | 1.8 (1.4-2.2) | 94 | 2.6 (2.0-3.2) | 609 | 25 | 4.8 (3.0-6.6) | 29 | 5.7 (3.6-7.8) | ||||
| Flow cytometry | 1005 | 3 | 0.5 (0-1.0) | 8 | 1.3 (0.4-2.2) | 115 | 4 | 3.9 (0.1-7.7) | 5 | 5.5 (0.6-10.4) | ||||
| Final risk group | .24 | .11 | .18 | .44 | ||||||||||
| Low | 3948 | 41 | 1.5 (1.0-2.0) | 50 | 2.1 (1.5-2.7) | – | – | – | – | – | – | – | ||
| Intermediate | 3860 | 38 | 1.9 (1.3-2.5) | 52 | 3.0 (2.1-3.9) | 683 | 29 | 4.9 (3.1-6.7) | 33 | 5.8 (3.8-7.8) | ||||
| High | 108 | 0 | 0 | 0 | 0 | 41 | 0 | 0 | 1 | 3.2 (0-9.9) | ||||
| Age at diagnosis, y | .23 | .35 | .62 | .74 | ||||||||||
| <1 | 132 | 3 | 3.2 (0.0-6.8) | 3 | 3.2 (0.0-6.8) | 2 | 0 | 0 | 0 | 0 | ||||
| 1-10 | 5989 | 65 | 1.6 (1.2-2.0) | 85 | 2.3 (1.8-2.8) | 492 | 22 | 5.0 (2.9-7.1) | 25 | 6.0 (3.7-8.3) | ||||
| >10 | 795 | 11 | 2.0 (0.8-3.2) | 14 | 2.8 (1.2-4.4) | 230 | 7 | 3.9 (1.0-6.8) | 9 | 5.2 (1.8-8.6) | ||||
| Sex | .02 | <.001 | .83 | .46 | ||||||||||
| Male | 3982 | 56 | 2.0 (1.5-2.5) | 76 | 3.1 (2.3-3.9) | 539 | 22 | 4.7 (2.7-6.7) | 27 | 6.2 (3.9-8.5) | ||||
| Female | 2934 | 23 | 1.1 (0.6-1.6) | 26 | 1.4 (0.8-2.0) | 185 | 7 | 4.3 (1.1-7.5) | 7 | 4.3 (1.1-7.5) | ||||
| Leukocyte count, ×109/L | .004 | <.001 | .002 | <.001 | ||||||||||
| <50 | 5732 | 56 | 1.4 (1.0-1.8) | 70 | 2.0 (1.5-2.5) | 294 | 4 | 1.7 (0-3.4) | 4 | 1.7 (0-3.4) | ||||
| ≥50 | 1184 | 23 | 2.9 (1.7-4.1) | 32 | 4.4 (2.8-6.0) | 430 | 25 | 6.7 (4.1-9.3) | 30 | 8.5 (5.5-11.5) | ||||
| CNS status | .93 | .50 | .87 | .09 | ||||||||||
| CNS1 | 6419 | 74 | 1.6 (1.2-2.0) | 93 | 2.2 (1.7-2.7) | 655 | 25 | 4.4 (2.7-6.1) | 28 | 5.2 (3.3-7.1) | ||||
| CNS2 | 100 | 1 | 1.5 (0-4.5) | 2 | 3.6 (0-8.6) | 16 | 1 | 6.7 (0-19.9) | 3 | 24.9 (0-52.3) | ||||
| Traumatic lumbar puncture | 342 | 3 | 1.4 (0-3.0) | 5 | 4.4 (0-9.2) | 32 | 2 | 6.5 (0-15.5) | 2 | 6.5 (0-15.5) | ||||
| CNS3 | 55 | 1 | 1.8 (0-5.4) | 2 | 3.8 (0-9.1) | 21 | 1 | 6.1 (0-18.0) | 1 | 6.1 (0-18.0) | ||||
| t(9;22)(BCR-ABL1) | <.001 | <.001 | .09 | .12 | ||||||||||
| Present | 329 | 13 | 6.8 (3.1-10.5) | 18 | 9.9 (5.2-14.6) | 6 | 1 | 16.7 (0-51.0) | 1 | 16.7 (0-51.0) | ||||
| Absent | 6587 | 66 | 1.4 (1.1-1.7) | 84 | 2.0 (1.5-2.5) | 718 | 28 | 4.5 (2.8-6.2) | 33 | 5.6 (3.7-7.5) | ||||
| t(12;21)(ETV6-RUNX1) | .11 | .02 | ||||||||||||
| Present | 1452 | 11 | 1.0 (0.4-1.6) | 12 | 1.2 (0.4-2.0) | – | – | – | – | – | – | – | ||
| Absent | 5464 | 68 | 1.8 (1.4-2.2) | 90 | 2.7 (2.1-3.3) | – | – | – | – | – | – | – | ||
| MRD on day 19 of induction, % | .90 | .90 | .11 | .09 | ||||||||||
| <0.01 | 3214 | 35 | 1.4 (0.9-1.9) | 44 | 2.1 (1.4-2.8) | 283 | 17 | 6.8 (3.6-10) | 20 | 8.5 (4.8-12.2) | ||||
| 0.01-0.09 | 1054 | 11 | 1.6 (0.7-2.5) | 14 | 2.0 (0.9-3.1) | 30 | 2 | 10.8 (0-26.1) | 2 | 10.8 (0-26.1) | ||||
| 0.1-0.99 | 1353 | 18 | 2.1 (1.1-3.1) | 21 | 2.5 (1.4-3.6) | 80 | 2 | 3.6 (0-8.7) | 3 | 5.3 (0-11.4) | ||||
| ≥1 | 1083 | 12 | 1.7 (0.7-2.7) | 18 | 3.3 (1.6-5.0) | 287 | 7 | 2.7 (0.7-4.7) | 8 | 3.3 (1.0-5.6) | ||||
| MRD on day 46 of induction, % | .40 | .15 | .37 | .51 | ||||||||||
| <0.01 | 5597 | 66 | 1.7 (0.7-2.7) | 82 | 2.4 (1.8-3.0) | 519 | 26 | 5.8 (3.6-8.0) | 30 | 6.9 (4.5-9.4) | ||||
| 0.01-0.09 | 483 | 3 | 0.9 (0-2.0) | 4 | 1.2 (0-2.4) | 42 | 1 | 2.7 (0-8.0) | 1 | 2.7 (0-8.0) | ||||
| 0.1-0.99 | 254 | 4 | 2.1 (0-4.2) | 7 | 4.4 (1.1-7.7) | 42 | 1 | 2.4 (0-7.1) | 1 | 2.4 (0-7.1) | ||||
| ≥1 | 103 | 0 | 0 | 0 | 0 | 41 | 0 | 0 | 1 | 3.2 (0-9.9) | ||||
| . | Univariate analysis . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable . | Patients with B-ALL . | Patients with T-ALL . | ||||||||||||
| No. total . | No. of isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, % (95% CI) . | P . | No. of any CNS relapse . | 5-y cumulative risk of any CNS relapse, % (95% CI) . | P . | No. total . | No. of isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, % (95% CI) . | P . | No. of any CNS relapse . | 5-y cumulative risk of any CNS relapse, % (95% CI) . | P . | |
| Intrathecal therapy with total intravenous anesthesia | .01 | .01 | .99 | .77 | ||||||||||
| No | 6120 | 77 | 1.8 (1.4-2.2) | 98 | 2.6 (2.0-3.2) | 649 | 26 | 4.6 (2.8-6.4) | 31 | 5.8 (3.8-7.8) | ||||
| Yes | 796 | 2 | 0.4 (0-1.1) | 4 | 1.1 (0-2.2) | 75 | 3 | 4.7 (0-10.0) | 3 | 4.7 (0-10.0) | ||||
| First CSF examination | .006 | .05 | .77 | .87 | ||||||||||
| Conventional cytology | 5911 | 76 | 1.8 (1.4-2.2) | 94 | 2.6 (2.0-3.2) | 609 | 25 | 4.8 (3.0-6.6) | 29 | 5.7 (3.6-7.8) | ||||
| Flow cytometry | 1005 | 3 | 0.5 (0-1.0) | 8 | 1.3 (0.4-2.2) | 115 | 4 | 3.9 (0.1-7.7) | 5 | 5.5 (0.6-10.4) | ||||
| Final risk group | .24 | .11 | .18 | .44 | ||||||||||
| Low | 3948 | 41 | 1.5 (1.0-2.0) | 50 | 2.1 (1.5-2.7) | – | – | – | – | – | – | – | ||
| Intermediate | 3860 | 38 | 1.9 (1.3-2.5) | 52 | 3.0 (2.1-3.9) | 683 | 29 | 4.9 (3.1-6.7) | 33 | 5.8 (3.8-7.8) | ||||
| High | 108 | 0 | 0 | 0 | 0 | 41 | 0 | 0 | 1 | 3.2 (0-9.9) | ||||
| Age at diagnosis, y | .23 | .35 | .62 | .74 | ||||||||||
| <1 | 132 | 3 | 3.2 (0.0-6.8) | 3 | 3.2 (0.0-6.8) | 2 | 0 | 0 | 0 | 0 | ||||
| 1-10 | 5989 | 65 | 1.6 (1.2-2.0) | 85 | 2.3 (1.8-2.8) | 492 | 22 | 5.0 (2.9-7.1) | 25 | 6.0 (3.7-8.3) | ||||
| >10 | 795 | 11 | 2.0 (0.8-3.2) | 14 | 2.8 (1.2-4.4) | 230 | 7 | 3.9 (1.0-6.8) | 9 | 5.2 (1.8-8.6) | ||||
| Sex | .02 | <.001 | .83 | .46 | ||||||||||
| Male | 3982 | 56 | 2.0 (1.5-2.5) | 76 | 3.1 (2.3-3.9) | 539 | 22 | 4.7 (2.7-6.7) | 27 | 6.2 (3.9-8.5) | ||||
| Female | 2934 | 23 | 1.1 (0.6-1.6) | 26 | 1.4 (0.8-2.0) | 185 | 7 | 4.3 (1.1-7.5) | 7 | 4.3 (1.1-7.5) | ||||
| Leukocyte count, ×109/L | .004 | <.001 | .002 | <.001 | ||||||||||
| <50 | 5732 | 56 | 1.4 (1.0-1.8) | 70 | 2.0 (1.5-2.5) | 294 | 4 | 1.7 (0-3.4) | 4 | 1.7 (0-3.4) | ||||
| ≥50 | 1184 | 23 | 2.9 (1.7-4.1) | 32 | 4.4 (2.8-6.0) | 430 | 25 | 6.7 (4.1-9.3) | 30 | 8.5 (5.5-11.5) | ||||
| CNS status | .93 | .50 | .87 | .09 | ||||||||||
| CNS1 | 6419 | 74 | 1.6 (1.2-2.0) | 93 | 2.2 (1.7-2.7) | 655 | 25 | 4.4 (2.7-6.1) | 28 | 5.2 (3.3-7.1) | ||||
| CNS2 | 100 | 1 | 1.5 (0-4.5) | 2 | 3.6 (0-8.6) | 16 | 1 | 6.7 (0-19.9) | 3 | 24.9 (0-52.3) | ||||
| Traumatic lumbar puncture | 342 | 3 | 1.4 (0-3.0) | 5 | 4.4 (0-9.2) | 32 | 2 | 6.5 (0-15.5) | 2 | 6.5 (0-15.5) | ||||
| CNS3 | 55 | 1 | 1.8 (0-5.4) | 2 | 3.8 (0-9.1) | 21 | 1 | 6.1 (0-18.0) | 1 | 6.1 (0-18.0) | ||||
| t(9;22)(BCR-ABL1) | <.001 | <.001 | .09 | .12 | ||||||||||
| Present | 329 | 13 | 6.8 (3.1-10.5) | 18 | 9.9 (5.2-14.6) | 6 | 1 | 16.7 (0-51.0) | 1 | 16.7 (0-51.0) | ||||
| Absent | 6587 | 66 | 1.4 (1.1-1.7) | 84 | 2.0 (1.5-2.5) | 718 | 28 | 4.5 (2.8-6.2) | 33 | 5.6 (3.7-7.5) | ||||
| t(12;21)(ETV6-RUNX1) | .11 | .02 | ||||||||||||
| Present | 1452 | 11 | 1.0 (0.4-1.6) | 12 | 1.2 (0.4-2.0) | – | – | – | – | – | – | – | ||
| Absent | 5464 | 68 | 1.8 (1.4-2.2) | 90 | 2.7 (2.1-3.3) | – | – | – | – | – | – | – | ||
| MRD on day 19 of induction, % | .90 | .90 | .11 | .09 | ||||||||||
| <0.01 | 3214 | 35 | 1.4 (0.9-1.9) | 44 | 2.1 (1.4-2.8) | 283 | 17 | 6.8 (3.6-10) | 20 | 8.5 (4.8-12.2) | ||||
| 0.01-0.09 | 1054 | 11 | 1.6 (0.7-2.5) | 14 | 2.0 (0.9-3.1) | 30 | 2 | 10.8 (0-26.1) | 2 | 10.8 (0-26.1) | ||||
| 0.1-0.99 | 1353 | 18 | 2.1 (1.1-3.1) | 21 | 2.5 (1.4-3.6) | 80 | 2 | 3.6 (0-8.7) | 3 | 5.3 (0-11.4) | ||||
| ≥1 | 1083 | 12 | 1.7 (0.7-2.7) | 18 | 3.3 (1.6-5.0) | 287 | 7 | 2.7 (0.7-4.7) | 8 | 3.3 (1.0-5.6) | ||||
| MRD on day 46 of induction, % | .40 | .15 | .37 | .51 | ||||||||||
| <0.01 | 5597 | 66 | 1.7 (0.7-2.7) | 82 | 2.4 (1.8-3.0) | 519 | 26 | 5.8 (3.6-8.0) | 30 | 6.9 (4.5-9.4) | ||||
| 0.01-0.09 | 483 | 3 | 0.9 (0-2.0) | 4 | 1.2 (0-2.4) | 42 | 1 | 2.7 (0-8.0) | 1 | 2.7 (0-8.0) | ||||
| 0.1-0.99 | 254 | 4 | 2.1 (0-4.2) | 7 | 4.4 (1.1-7.7) | 42 | 1 | 2.4 (0-7.1) | 1 | 2.4 (0-7.1) | ||||
| ≥1 | 103 | 0 | 0 | 0 | 0 | 41 | 0 | 0 | 1 | 3.2 (0-9.9) | ||||
| . | Multivariate analysis . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable . | Patients with B-ALL . | Patients with T-ALL . | ||||||||||||
| No. total . | No. isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, HR (95% CI) . | P . | No. any CNS relapse . | 5-y cumulative risk of any CNS relapse, HR (95% CI) . | P . | No. total . | No. isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, HR (95% CI) . | P . | No. any CNS relapse . | 5-y cumulative risk of any CNS relapse, HR (95% CI) . | P . | |
| Intrathecal therapy with total intravenous anesthesia | ||||||||||||||
| No | 5660 | 71 | 1 | 89 | 1 | – | – | – | – | – | – | – | ||
| Yes | 777 | 2 | 0.2 (0.04-0.7) | .02 | 4 | 0.3 (0.1-0.8) | .02 | – | – | – | – | – | – | – |
| First CSF examination | ||||||||||||||
| Conventional cytology | 5457 | 70 | 1 | 85 | 1 | – | – | – | – | – | – | – | ||
| Flow cytometry | 980 | 3 | 0.2 (0.06-0.6) | .006 | 8 | 0.5 (0.2-0.9) | .03 | – | – | – | – | – | – | – |
| Sex | ||||||||||||||
| Female | 2737 | 20 | 1 | 23 | 1 | – | – | – | – | – | – | – | ||
| Male | 3700 | 53 | 1.8 (1.1-3.0) | .03 | 70 | 2.1 (1.3-3.3) | .003 | – | – | – | – | – | – | – |
| Leukocyte count, ×109/L | ||||||||||||||
| <50 | 5378 | 54 | 1 | 67 | 1 | 261 | 4 | 1 | 4 | 1 | ||||
| ≥50 | 1059 | 19 | 1.3 (0.8-2.3) | .32 | 26 | 1.5 (0.9-2.3) | 0.12 | 383 | 24 | 4.3 (1.5-12.2) | .007 | 29 | 5.2 (1.8-14.9) | .002 |
| t(9;22)(BCR-ABL1) | ||||||||||||||
| Absent | 6135 | 13 | 1 | 76 | 1 | 638 | 27 | 1 | 32 | 1 | ||||
| Present | 302 | 60 | 3.8 (2.0-7.3) | <.001 | 17 | 3.7 (2.1-6.3) | <.001 | 6 | 1 | 4.6 (0.6-36.1) | .15 | 1 | 4.1 (0.5-32.9) | .18 |
| t(12;21)(ETV6-RUNX1) | ||||||||||||||
| Present | 1452 | 11 | 1 | 12 | 1 | – | – | – | – | – | – | – | ||
| Absent | 5464 | 62 | 1.3 (0.7-2.5) | .46 | 81 | 1.5 (0.8-2.9) | 0.17 | – | – | – | – | – | – | – |
| . | Multivariate analysis . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable . | Patients with B-ALL . | Patients with T-ALL . | ||||||||||||
| No. total . | No. isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, HR (95% CI) . | P . | No. any CNS relapse . | 5-y cumulative risk of any CNS relapse, HR (95% CI) . | P . | No. total . | No. isolated CNS relapse . | 5-y cumulative risk of isolated CNS relapse, HR (95% CI) . | P . | No. any CNS relapse . | 5-y cumulative risk of any CNS relapse, HR (95% CI) . | P . | |
| Intrathecal therapy with total intravenous anesthesia | ||||||||||||||
| No | 5660 | 71 | 1 | 89 | 1 | – | – | – | – | – | – | – | ||
| Yes | 777 | 2 | 0.2 (0.04-0.7) | .02 | 4 | 0.3 (0.1-0.8) | .02 | – | – | – | – | – | – | – |
| First CSF examination | ||||||||||||||
| Conventional cytology | 5457 | 70 | 1 | 85 | 1 | – | – | – | – | – | – | – | ||
| Flow cytometry | 980 | 3 | 0.2 (0.06-0.6) | .006 | 8 | 0.5 (0.2-0.9) | .03 | – | – | – | – | – | – | – |
| Sex | ||||||||||||||
| Female | 2737 | 20 | 1 | 23 | 1 | – | – | – | – | – | – | – | ||
| Male | 3700 | 53 | 1.8 (1.1-3.0) | .03 | 70 | 2.1 (1.3-3.3) | .003 | – | – | – | – | – | – | – |
| Leukocyte count, ×109/L | ||||||||||||||
| <50 | 5378 | 54 | 1 | 67 | 1 | 261 | 4 | 1 | 4 | 1 | ||||
| ≥50 | 1059 | 19 | 1.3 (0.8-2.3) | .32 | 26 | 1.5 (0.9-2.3) | 0.12 | 383 | 24 | 4.3 (1.5-12.2) | .007 | 29 | 5.2 (1.8-14.9) | .002 |
| t(9;22)(BCR-ABL1) | ||||||||||||||
| Absent | 6135 | 13 | 1 | 76 | 1 | 638 | 27 | 1 | 32 | 1 | ||||
| Present | 302 | 60 | 3.8 (2.0-7.3) | <.001 | 17 | 3.7 (2.1-6.3) | <.001 | 6 | 1 | 4.6 (0.6-36.1) | .15 | 1 | 4.1 (0.5-32.9) | .18 |
| t(12;21)(ETV6-RUNX1) | ||||||||||||||
| Present | 1452 | 11 | 1 | 12 | 1 | – | – | – | – | – | – | – | ||
| Absent | 5464 | 62 | 1.3 (0.7-2.5) | .46 | 81 | 1.5 (0.8-2.9) | 0.17 | – | – | – | – | – | – | – |