Table 4.
Univariate and multivariable analyses of risk factors on overall survival post relapse.
| Variables | B-ALL | T-ALL | Infant ALL | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| univariate | multivariable | univariate | multivariable | univariate | multivariable | |||||||
| HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | |
| Time to relapse | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | ||||||
| Early (<18mo) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| Intermediate (18–36mo) | 0.46 (0.39–0.55) | 0.47 (0.40–0.57) | 0.74 (0.48–1.13) | 0.53 (0.34–0.85) | 0.27 (0.15–0.48) | 0.16 (0.08–0.31) | ||||||
| Late (≥36mo) | 0.26 (0.22–0.31) | 0.21 (0.17–0.26) | 0.33 (0.18–0.59) | 0.23 (0.12–0.43) | 0.23 (0.06–0.94) | 0.16 (0.03–0.71) | ||||||
| Relapse site | <0.001 | <0.001 | <0.001 | <0.001 | 0.016 | 0.002 | ||||||
| Isolated BM | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| Combined BM ( ± CNS) | 0.65 (0.52–0.81) | 0.74 (0.60–0.93) | 1.14 (0.73–1.80) | 0.98 (0.59–1.61) | 0.88 (0.45–1.71) | 0.71 (0.34–1.49) | ||||||
| Isolated CNS | 0.53 (0.44–0.64) | 0.32 (0.26–0.39) | 0.41 (0.27–0.62) | 0.27 (0.17–0.43) | 0.35 (0.17–0.74) | 0.23 (0.10–0.55) | ||||||
| Other | 0.51 (0.36–0.72) | 0.49 (0.35–0.70) | 0.50 (0.29–0.87) | 0.49 (0.27–0.89) | 0.66 (0.33–1.33) | 1.46 (0.67–3.16) | ||||||
| Sex | 0.84 | 0.36 | 0.67 | 0.98 | 0.052 | 0.023 | ||||||
| Male | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| Female | 0.99 (0.86–1.13) | 0.93 (0.81–1.08) | 0.92 (0.62–1.36) | 0.99 (0.65–1.53) | 1.52 (1.00–2.32) | 1.81 (1.08–3.02) | ||||||
| WBC at initial diagnosis (per µL) | <0.001 | 0.096 | 0.22 | 0.058 | 0.81 | 0.72 | ||||||
| <50,000 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| 50,000–100,000 | 0.89 (0.69–1.14) | 0.86 (0.66–1.11) | 1.00 (0.56–1.79) | 1.40 (0.73–2.71) | 0.90 (0.44–1.83) | 1.25 (0.55–2.80) | ||||||
| ≥100,000 | 1.60 (1.33–1.93) | 1.18 (0.96–1.45) | 1.34 (0.93–1.95) | 1.69 (1.09–2.61) | 1.08 (0.63–1.86) | 0.94 (0.48–1.85) | ||||||
| Age at initial diagnosis (non-infant) | <0.001 | <0.001 | 0.002 | 0.002 | Not applicable | Not applicable | ||||||
| 1–9 years | 1 | 1 | 1 | 1 | ||||||||
| 10–15 years | 1.92 (1.63–2.26) | 1.59 (1.33–1.89) | 1.98 (1.37–2.86) | 2.00 (1.34–2.99) | ||||||||
| ≥16 years | 2.30 (1.88–2.83) | 1.75 (1.40–2.18) | 1.43 (0.85–2.43) | 1.89 (1.07–3.35) | ||||||||
| Age at relapsea | <0.001 | Excluded due to correlation with age at diagnosis | 0.057 | Excluded due to correlation with age at diagnosis | 0.002 | Excluded due to correlation with age at diagnosis | ||||||
| <1 year | - | 1 | ||||||||||
| 1–9 years | 1 | 1 | 0.37 (0.21-0.65) | |||||||||
| 10–15 years | 1.23 (1.04–1.45) | 1.08 (0.74–1.59) | ||||||||||
| ≥16 years | 1.61 (1.36–1.91) | 1.70 (1.11–2.60) | ||||||||||
| CNS status at initial dx | 0.12 | 0.85 | 0.19 | 0.49 | 0.49 | 0.29 | ||||||
| CNS 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| CNS 2 | 1.14 (0.93–1.39) | 0.98 (0.80–1.21) | 0.94 (0.61–1.44) | 0.96 (0.59–1.57) | 0.83 (0.52–1.32) | 1.04 (0.60–1.80) | ||||||
| CNS 3 | 1.48 (0.96–2.29) | 0.88 (0.56–1.38) | 0.61 (0.35–1.07) | 0.72 (0.39–1.32) | 1.18 (0.65–2.14) | 1.77 (0.85–3.65) | ||||||
| Race/Ethnicity | 0.003 | 0.13 | 0.74 | 0.46 | 0.68 | 0.025 | ||||||
| Non-Hispanic White | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
| Hispanic of all races | 1.39 (1.19–1.63) | 1.26 (1.07–1.49) | 0.87 (0.48–1.57) | 0.91 (0.48–1.71) | 0.72 (0.39–1.35) | 0.52 (0.25–1.09) | ||||||
| Non-Hispanic Black | 1.28 (0.98–1.67) | 1.21 (0.92–1.60) | 0.88 (0.49–1.59) | 0.71 (0.38–1.34) | 0.52 (0.21–1.31) | 0.23 (0.08–0.64) | ||||||
| Non-Hispanic Asian | 1.25 (0.84–1.85) | 1.12 (0.75–1.68) | 1.47 (0.59–3.64) | 2.04 (0.78–5.35) | 0.79 (0.31–1.96) | 1.20 (0.43–3.34) | ||||||
| Non-Hispanic Other | 1.34 (0.66–2.69) | 1.04 (0.51–2.12) | 1.03 (0.14–7.40) | 3.15 (0.35–28.61) | 0.88 (0.28–2.82) | 1.68 (0.47–6.03) | ||||||
| Other/Unknown | 1.03 (0.77–1.36) | 1.04 (0.78–1.38) | 1.26 (0.85–1.86) | 1.07 (0.70–1.63) | 0.82 (0.35–1.91) | 0.69 (0.29–1.66) | ||||||
| NCI risk groupb | <0.001 | Excluded due to correlation with age and WBC at diagnosis | Not assessed | Not assessed | ||||||||
| Standard risk | 1 | |||||||||||
| High risk | 1.67 (1.45–1.91) | |||||||||||
| Induction Day 29 MRDb | <0.001 | 0.010 | Not assessed | Not assessed | ||||||||
| <0.01%c | 1 | 1 | ||||||||||
| 0.01–0.099% | 1.02 (0.85–1.23) | 0.98 (0.81–1.19) | ||||||||||
| 0.1–0.99% | 1.54 (1.26–1.90) | 1.20 (0.97–1.49) | ||||||||||
| ≥1.0% | 2.22 (1.74–2.84) | 1.41 (1.09–1.84) | ||||||||||
| Unknown | 1.22 (0.99–1.50) | 1.34 (1.02–1.75) | ||||||||||
| Trisomy 4 + 10b | <0.001 | 0.004 | Not applicable | Not applicable | ||||||||
| Negative | 1 | 1 | ||||||||||
| Positive | 0.54 (0.41–0.72) | 0.66 (0.50–0.88) | ||||||||||
| ETV6::RUNX1b | <0.001 | 0.001 | Not applicable | Not applicable | ||||||||
| Negative | 1 | 1 | ||||||||||
| Positive | 0.42 (0.32–0.54) | 0.62 (0.46–0.82) | ||||||||||
| KMT2A-Rb | <0.001 | 0.050 | Not applicable | 0.012 | 0.62 | |||||||
| Negative | 1 | 1 | 1 | 1 | ||||||||
| Positive | 2.04 (1.38–3.02) | 1.52 (1.00–2.29) | 2.40 (1.11–5.20) | 1.24 (0.52–2.94) | ||||||||
| Hypodiploidb | <0.001 | 0.002 | Not applicable | Not applicable | ||||||||
| Negative | 1 | 1 | ||||||||||
| Positive | 4.84 (3.33–7.03) | 1.85 (1.25–2.75) | ||||||||||
| BCR::ABL1b | 0.044 | Not significant; Excludedd | Not applicable | Not applicable | ||||||||
| Negative | 1 | |||||||||||
| Positive | 1.42 (1.01–1.99) | |||||||||||
| TCF3::PBX1b | 0.029 | Not significant; Excludedd | Not applicable | Not applicable | ||||||||
| Negative | 1 | |||||||||||
| Positive | 1.46 (1.04–2.05) | |||||||||||
| iAMP21b | 0.99 | Not significant; Excludedd | Not applicable | Not applicable | ||||||||
| No | 1 | |||||||||||
| Yes | 1.00 (0.67–1.50) | |||||||||||
| B-ALL, otherb | <0.001 | Excluded due to correlation with the above cytogenetic variables | Not applicable | Not applicable | ||||||||
| No | 1 | |||||||||||
| Yes | 1.32 (1.12–1.55) | |||||||||||
ALL Acute Lymphoblastic Leukemia, BM Bone Marrow, CI Confidence Interval, CNS Central Nervous System, HR Hazard Ratio, MRD Minimal Residual Disease, NCI National Cancer Institute, WBC White Blood Cell Count.
aAge at relapse was associated with OS post relapse in univariate analysis and was excluded from multivariable analysis due to correlation with age at diagnosis. A sensitivity multivariable analysis (not reported) that included age at relapse did not render a significant p value for this variable.
bCharacteristics at original diagnosis.
cIncluded 11 patients with negative MRD with assay of sensitivity of 1/1000.
dNo significant association was found between the three cytogenetic variables and survival post relapse after adjusting for other variables. Due to small sample size in subcategories of the cytogenetic variables, the three cytogenetic variables were excluded from the multivariable model.