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Table 4 Estimated hazard ratiosa from the multivariable Cox proportional model on event-free survival and hazard of relapse in patients of the discovery cohort

From: Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group

Variable

Eventb

Relapse

Hazard Ratio (95% CI)

P(X2)

Hazard Ratio (95% CI)

P(X2)

rs6744284 TTc

0.56 (0.27-1.13)

0.103

0.40 (0.09-1.84)

0.240

Bilirubin CTC grades 3-4d

2.67 (1.59-4.48)

< 0.001

4.61 (1.71-12.42)

0.003

ALT/AST CTC grade 4e

1.17 (0.60-2.27)

0.643

0.43 (0.06-3.29)

0.417

MRD standard-riskf

0.94 (0.57-1.54)

0.798

1.10 (0.37-3.24)

0.870

MRD high-riskf

4.52 (2.73-7.48)

< 0.001

6.52 (2.41-17.66)

< 0.001

Slow early responseg

2.60 (1.35-5.00)

0.004

2.21 (0.48-10.17)

0.311

Poor prednisone responseh

1.38 (0.82-2.32)

0.223

2.09 (0.77-5.64)

0.148

Initial WBC count ≥100,000/μLi

1.48 (0.92-2.39)

0.109

1.18 (0.43-3.22)

0.750

  1. a Hazard ratios (HR) are given as indicated with the corresponding 95% confidence intervals (CI), all patients of the discovery cohort with complete information were included (n = 642) in this analyses
  2. b Events were resistance to therapy (non-response), relapse, secondary neoplasm or death from any cause. Failure to achieve remission due to early death or non-response was considered as event at time zero
  3. c Compared to rs6744284 wild-type (CC) or heterozygous (TC) genotypes
  4. d Compared to bilirubin grades 0 to 2 of the Common Toxicity Criteria of the National Cancer Institute version 2 (CTC)
  5. e Compared to CTC grades 0 to 3 of alanine (ALT) or aspartate (AST) transaminase serum levels
  6. f Minimal residual disease (MRD) standard-risk patients were negative on treatment days 33 and 78; MRD high-risk patients had a leukemic cell load ≥5 × 10−4 on treatment day 78; all other results were classified MRD intermediate-risk. MRD standard- or high-risk compared with MRD intermediate-risk
  7. g HR compared with MRD intermediate-risk patients with no slow early response
  8. h Leukemic blasts ≥1000/μL in the peripheral blood on treatment day 8. HR compared to patients with < 1000/μL leukemic blasts (prednisone good responders)
  9. i White blood cell (WBC) count at diagnosis ≥100,000 /μL. HR compared to patients with WBC counts < 100,000 /μL