Table 3. Multivariable Analysis of Genetic Ancestries for Association With Survival and Relapse Outcomes for the Entire Cohort.
| Prognostic factor | Event-free survival | Overall survival | Cumulative incidence of relapse | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | P valuea | HR (95% CI) | P valuea | HR (95% CI) | P valuea | |
| Age at diagnosis, y | ||||||
| <1 | 2.4 (1.1-5.0) | .06 | 4.3 (1.6-11.6) | .001 | 1.0 (0.4-2.6) | .93 |
| ≥1 to <10 | 1 [Reference] | 1 [Reference] | 1 [Reference] | |||
| ≥10 | 1.2 (0.9-1.6) | 1.7 (1.2-2.6) | 1.0 (0.7-1.4) | |||
| Leukocyte count at diagnosis, cells/µL | ||||||
| <50 000 | 1 [Reference] | .006 | 1 [Reference] | .04 | 1 [Reference] | .007 |
| ≥50 000 | 1.5 (1.1-2.1) | 1.5 (1.0-2.3) | 1.6 (1.1-2.4) | |||
| Biological subtypesb | ||||||
| ETV6-RUNX1 | 1 [Reference] | <.001 | 1 [Reference] | <.001 | 1 [Reference] | <.001 |
| DUX4 | 1.8 (0.7-4.4) | 1.5 (0.4-6.6) | 2.2 (0.8-6.2) | |||
| Hyperdiploid | 2.0 (1.0-3.8) | 1.9 (0.7-5.4) | 2.1 (1-4.6) | |||
| ZNF384 | 2.9 (0.9-8.9) | 3.4 (0.6-17.9) | 2.9 (0.8-10.9) | |||
| B other | 3.4 (1.7-6.8) | 3.8 (1.3-10.7) | 4.7 (2.1-10.7) | |||
| CRLF2 | 7.2 (3.4-15.0) | 8.8 (3.0-26.2) | 5.4 (2.2-13.5) | |||
| ETV6-RUNX1–like | 6.3 (2.7-14.9) | 9.4 (2.8-31.1) | 5.2 (1.9-14.4) | |||
| KMT2A | 6.5 (2.9-14.7) | 6.7 (2.0-22.5) | 9.9 (3.9-24.8) | |||
| Low hypodiploid | 10.0 (3.7-27.5) | 17.4 (5.0-60.4) | 20.0 (6.9-58.0) | |||
| MEF2D | 4.5 (1.3-15.8) | 6.8 (1.3-35.7) | 3.4 (0.7-16.9) | |||
| Near haploid | 12.2 (3.9-38.1) | 35.0 (9.0-136.0) | 8.7 (1.9-39.9) | |||
| PAX5alt | 3.5 (1.6-7.5) | 2.0 (0.5-7.7) | 5.1 (2.2-12.2) | |||
| BCR-ABL1 | 7.4 (3.3-16.5) | 7.4 (2.3-24.1) | 7.5 (2.8-20.1) | |||
| BCR-ABL1–like | 6.9 (3.1-15.4) | 7.3 (2.3-23.5) | 6.7 (2.6-17.2) | |||
| T-ALL | 4.8 (2.5-9.0) | 6.3 (2.4-16.9) | 4.0 (1.8-9) | |||
| TCF3-PBX1 | 2.3 (1.0-5.3) | 3.5 (1.0-11.5) | 2.4 (0.9-6.4) | |||
| Percentage genetic ancestryc | ||||||
| European | 1 [Reference] | 1 [Reference] | 1 [Reference] | |||
| African (every 25% increase) | 1.2 (1.1-1.4) | .005 | 1.2 (1.01-1.4) | .04 | 1.3 (1.1-1.5) | .006 |
| Native American (every 25% increase) | 1.3 (1.01-1.6) | .04 | 1.4 (1.01-1.9) | .04 | 1.2 (0.9-1.6) | .16 |
| East Asian (every 25% increase) | 1.0 (0.7-1.4) | .87 | 1.0 (0.7-1.6) | .88 | 1.0 (0.7-1.5) | .96 |
| South Asian (every 25% increase) | 0.9 (0.7-1.3) | .70 | 1.0 (0.7-1.6) | .98 | 0.8 (0.5-1.3) | .42 |
Abbreviations: ALL, acute lymphoblastic leukemia; HR, hazard ratio; T-ALL, T-cell ALL.
SI conversion factor: To convert leukocytes to cells × 109/L, multiply by 0.001.
P value for event-free survival and overall survival determined by Cox proportional hazards regression test and P value for cumulative incidence of any relapse determined by Fine-Gray competing risks regression. Treatment protocol was included as a covariate for all analyses. Because each cohort and site had their own ALL protocol, this adjusted for potential confounding effects arising from differences in treatment and other factors across sites.
Subtypes with fewer than 10 patients (ie, NUTM1 and PAX5 P80R) in the whole outcomes cohort were combined into B other.
Percentage genetic ancestry assessed as a continuous variable with each ancestry varying from 0% to 100%. The 4 non-European ancestries were included in the model, leaving European ancestry out as a reference. Hazard ratios are represented for every 25% increase in ancestry; for example, for every 25% increase in African ancestry with corresponding 25% decrease in European ancestry (and remaining ancestries fixed), there is a 1.2-fold increase in risk of event and 1.3-fold increase in risk of relapse.