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Table 1 Characteristics of 1547 patients according to serum bilirubin levels during induction/consolidation therapy for acute lymphoblastic leukemia

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

  

Patients without hyperbilirubinemia

Patients with hyperbilirubinemia

Pa

  

(n = 540)

(%)

(n = 1007)

(%)

Sex

Male

300

(56%)

561

(56%)

 

Female

240

(44%)

446

(44%)

0.954

Age at diagnosis of ALL [y]

< 6

372

(69%)

483

(48%)

 

≥6 < 10

93

(17%)

205

(20%)

 

≥10

75

(14%)

319

(32%)

< 0.001

Immunophenotype

B cell ALL

461

(85%)

833

(83%)

 

T cell ALL

55

(10%)

146

(14%)

0.022

Other/not characterizedb

24

(4%)

28

(3%)

 

White blood cell count at diagnosis of ALL [/μL]

< 10,000

261

(48%)

488

(48%)

 

≥10,000 < 50,000

187

(35%)

323

(32%)

 

≥50,000 < 100,000

52

(10%)

95

(9%)

 

≥100,000

40

(7%)

100

(10%)

0.364

Unknown

0

(0%)

1

(0%)

 

CNS positivityc

No

508

(94%)

932

(93%)

 

Yes

13

(2%)

33

(3%)

0.326

Unknown

19

(4%)

42

(4%)

 

Hyperdiploidyd

No

303

(56%)

627

(62%)

 

Yes

105

(19%)

138

(14%)

0.002

Unknown

132

(24%)

242

(24%)

 

ETV6-RUNX1 rearrangement

Negative

380

(70%)

688

(68%)

 

Positive

120

(22%)

231

(23%)

0.636

Unknown

40

(7%)

88

(9%)

 

BCR-ABL1 rearrangement

Positive

8

(1%)

20

(2%)

 

Negative

500

(93%)

941

(93%)

0.500

Unknown

32

(6%)

46

(5%)

 

KMT2A-AFF1 rearrangement

Positive

2

(0%)

4

(0%)

 

Negative

471

(87%)

890

(88%)

0.948

Unknown

67

(12%)

113

(11%)

 

Prednisone responsee

Good

492

(91%)

898

(89%)

 

Poor

40

(7%)

96

(10%)

0.162

Unknown

8

(1%)

13

(1%)

 

MRD risk groupf

Standard

223

(41%)

428

(43%)

 

Intermediate

251

(46%)

432

(43%)

 

High

32

(6%)

72

(7%)

0.393

Unknown

34

(6%)

75

(7%)

 

Final risk groupg

Standard

167

(31%)

318

(32%)

 

Intermediate

303

(56%)

532

(53%)

 

High

69

(13%)

156

(15%)

0.282

Other/Unknown

1

(0%)

1

(0%)

 

Maximum transaminase levels during protocols IA/IBh

CTC grade 0

71

(13%)

25

(2%)

 

CTC grades 1-2

249

(46%)

429

(43%)

 

CTC grades 3-4

212

(39%)

553

(55%)

< 0.001

Unknown

8

(1%)

0

(0%)

 

Maximum bilirubin levels during protocol IAi

CTC grade 0

499

(92%)

121

(12%)

 

CTC grades 1-2

0

(0%)

707

(70%)

 

CTC grades 3-4

0

(0%)

158

(16%)

< 0.001

Unknown

41

(8%)

21

(2%)

 

Maximum bilirubin levels during protocol IBi

CTC grade 0

501

(93%)

342

(34%)

 

CTC grades 1-2

0

(0%)

575

(57%)

 

CTC grades 3-4

0

(0%)

50

(5%)

< 0.001

Unknown

39

(7%)

40

(4%)

 

Maximum bilirubin levels during protocol IA/IBi

CTC grade 0

540

(100%)

0

(0%)

 

CTC grades 1-2

0

(0%)

825

(82%)

 

CTC grades 3-4

0

(0%)

182

(18%)

< 0.001

Maximum bilirubin levels during the entire course of therapyj

CTC grade 0

412

(76%)

0

(0%)

 

CTC grades 1-2

123

(23%)

767

(76%)

 

CTC grades 3-4

5

(1%)

240

(24%)

< 0.001

  1. Abbreviations: CNS central nervous system, CTC Common Toxicity Criteria of the National Cancer Institute version 2, UNL Upper normal limit
  2. aP-values resulting from X2 or Fisher’s exact test: Patients of the study cohort with hyperbilirubinemia, i.e. bilirubin levels > 17.1 μmol/L (UNL) during induction and/or consolidation (protocols IA/IB) of the AIEOP-BFM ALL protocol (CTC grades 1-4, cases) versus patients with normal levels ≤17.1 μmol/L (CTC grade 0, controls)
  3. b One patient was diagnosed with acute undifferentiated leukemia and no immunophenotype information was available for 51 patients
  4. c CNS negative, puncture nontraumatic without leukemic blasts in the cerebrospinal fluid (CSF) after cytocentrifugation; CNS positive, puncture nontraumatic with > 5 leukocytes /μL in the CSF with identifiable blasts
  5. d Defined by cytogenetics (> 50 chromosomes) or by flow cytometric analyses of the ratio of DNA content of leukemic G0/G1 cells to normal diploid lymphocytes (≥1.16)
  6. e Good < 1000 leukemic blasts/μL peripheral blood on treatment day 8; poor ≥1000 blasts/μL
  7. f Risk stratification based on minimal residual disease (MRD) analysis for ERG: Standard risk, MRD-negative on treatment day 33 and 78; high risk, leukemic cell load ≥5 × 10−4 on treatment day 78; all other results correspond to intermediate risk
  8. g Treatment group according to risk stratification including all relevant diagnostic parameters
  9. h Toxicity grading of the alanine and aspartate transaminase serum activity levels during induction/consolidation (protocols IA/IB) was according to CTC, considering 20 U/L as the UNL
  10. i Bilirubin toxicity grading during induction/consolidation (protocols IA/IB) was according to the CTC, with grade 0 corresponding to total serum levels ≤UNL, grade 1 to levels >UNL to 1.5xUNL, grade 2 levels > 1.5x UNL to 3.0x UNL, grade 3 levels > 3.0x UNL to 10.0x UNL and grade 4 to levels > 10.0x UNL
  11. j The highest individual bilirubin toxicity level throughout the entire treatment course under investigation (compare Suppl. Fig. 4). Toxicity grading was as above (CTC)
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Journal of Experimental & Clinical Cancer Research

ISSN: 1756-9966

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