J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://jh.elmerpub.com

Original Article

Volume 000, Number 000, March 2025, pages 000-000

Post-Induction Minimal Residual Disease in Pediatric Pre-B-Cell Acute Lymphoblastic Leukemia: A Step Towards Precision Medicine?

**Table 1.** Clinical Characteristics of the Patients
Parameters of interest	At induction (n = 108)	Post-consolidation (n = 27)
CNS: central nervous system; WBC: white blood cell.
Gender
Male	52 (48.1%)	13 (48.1%)
Female	56 (51.9%)	14 (51.9%)
Age at diagnosis (years), median (range)	4.3 (1.1 - 13.9)	4.0 (1.5 - 13.9)
≤ 10 years	91 (84.3%)	22 (81.5%)
> 10 years	17 (15.7%)	5 (18.5%)
WBC at presentation (× 10⁹/L)	11.6 (1.0 - 395.8)	16 (1.1 - 395.8)
< 50 × 10⁹/L	88 (81.5%)	20 (74.1%)
50 - 100 × 10⁹/L	10 (9.3%)	3 (11.1%)
> 100 × 10⁹/L	10 (9.3%)	4 (14.8%)
CNS status
CNS-1	91 (84.3%)	24 (88.9%)
CNS-2	13 (12.0%)	2 (7.4%)
CNS-3	4 (3.7%)	1 (3.7%)
Risk stratification
Standard risk	66 (61.1%)	14 (51.9%)
High risk	42 (38.9%)	13 (48.1%)
Treatment protocols
AALL0232	44 (40.7%)	14 (51.9%)
AALL0331	64 (59.3%)	13 (48.1%)
Testicular disease (+)	1 (1.9%)	None
Molecular/cytogenetic
Favorable	92/100 (92.0%)	23 (85.2%)
Unfavorable	8/100 (8.0%)	4 (14.8%)

Table 1. Clinical Characteristics of the Patients

Parameters of interest

At induction (n = 108)

Post-consolidation (n = 27)

CNS: central nervous system; WBC: white blood cell.

Gender

Male

52 (48.1%)

13 (48.1%)

Female

56 (51.9%)

14 (51.9%)

Age at diagnosis (years), median (range)

4.3 (1.1 - 13.9)

4.0 (1.5 - 13.9)

≤ 10 years

91 (84.3%)

22 (81.5%)

> 10 years

17 (15.7%)

5 (18.5%)

WBC at presentation (× 10⁹/L)

11.6 (1.0 - 395.8)

16 (1.1 - 395.8)

< 50 × 10⁹/L

88 (81.5%)

20 (74.1%)

50 - 100 × 10⁹/L

10 (9.3%)

3 (11.1%)

> 100 × 10⁹/L

10 (9.3%)

4 (14.8%)

CNS status

CNS-1

91 (84.3%)

24 (88.9%)

CNS-2

13 (12.0%)

2 (7.4%)

CNS-3

4 (3.7%)

1 (3.7%)

Risk stratification

Standard risk

66 (61.1%)

14 (51.9%)

High risk

42 (38.9%)

13 (48.1%)

Treatment protocols

AALL0232

44 (40.7%)

14 (51.9%)

AALL0331

64 (59.3%)

13 (48.1%)

Testicular disease (+)

1 (1.9%)

None

Molecular/cytogenetic

Favorable

92/100 (92.0%)

23 (85.2%)

Unfavorable

8/100 (8.0%)

4 (14.8%)

**Table 2.** Post-Induction MRD With Clinical and Biological Risk Factors (n = 108)
Parameters of interest	MRD (-)	MRD (+)	Total	P-value
CNS: central nervous system; MRD: minimal residual disease; WBC: white blood cell.
Gender				0.527
Male	36 (46.2%)	16 (53.3%)	52 (48.1%)
Female	42 (53.8%)	14 (46.7%)	56 (51.9%)
Age at diagnosis (years), median (range)	4.3 (1.1 - 13.3)	4.0 (1.5 - 13.9)	4.3 (1.1 - 13.9)	0.959
≤ 10 years	66 (84.6%)	25 (83.3%)	91 (84.3%)	1.000
> 10 years	12 (15.4%)	5 (16.7%)	17 (15.7%)
WBC at presentation (× 10⁹/L)	10.6 (1.0 - 200.0)	14.4 (1.0 - 395.8)	11.6 (1.0 - 395.8)	0.387
< 50 × 10⁹/L	65 (83.3%)	23 (76.7%)	88 (81.5%)	0.607
50 - 100 × 10⁹/L	7 (9.0%)	3 (10.0%)	10 (9.3%)
> 100 × 10⁹/L	6 (7.7%)	4 (13.3%)	10 (9.3%)
CNS status				0.721
CNS-1	64 (82.1%)	27 (90.0%)	91 (84.3%)
CNS-2	11 (14.1%)	2 (6.7%)	13 (12.0%)
CNS-3	3 (3.8%)	1 (3.3%)	4 (3.7%)
Risk stratification				0.660
Standard risk	49 (62.8%)	17 (56.7%)	66 (61.1%)
High risk	29 (37.2%)	13 (43.3%)	42 (38.9%)
Treatment protocols				0.514
AALL0232	30 (38.5%)	14 (46.7%)	44 (40.7%)
AALL0331	48 (61.5%)	16 (53.3%)	64 (59.3%)
Molecular/cytogenetic studies				0.236
Favorable	66 (94.3%)	26 (86.7%)	92 (92.0%)
Unfavorable	4 (5.7%)	4 (13.3%)	8 (8.0%)

Table 2. Post-Induction MRD With Clinical and Biological Risk Factors (n = 108)

Parameters of interest

MRD (-)

MRD (+)

Total

P-value

CNS: central nervous system; MRD: minimal residual disease; WBC: white blood cell.

Gender

0.527

Male

36 (46.2%)

16 (53.3%)

52 (48.1%)

Female

42 (53.8%)

14 (46.7%)

56 (51.9%)

Age at diagnosis (years), median (range)

4.3 (1.1 - 13.3)

4.0 (1.5 - 13.9)

4.3 (1.1 - 13.9)

0.959

≤ 10 years

66 (84.6%)

25 (83.3%)

91 (84.3%)

1.000

> 10 years

12 (15.4%)

5 (16.7%)

17 (15.7%)

WBC at presentation (× 10⁹/L)

10.6 (1.0 - 200.0)

14.4 (1.0 - 395.8)

11.6 (1.0 - 395.8)

0.387

< 50 × 10⁹/L

65 (83.3%)

23 (76.7%)

88 (81.5%)

0.607

50 - 100 × 10⁹/L

7 (9.0%)

3 (10.0%)

10 (9.3%)

> 100 × 10⁹/L

6 (7.7%)

4 (13.3%)

10 (9.3%)

CNS status

0.721

CNS-1

64 (82.1%)

27 (90.0%)

91 (84.3%)

CNS-2

11 (14.1%)

2 (6.7%)

13 (12.0%)

CNS-3

3 (3.8%)

1 (3.3%)

4 (3.7%)

Risk stratification

0.660

Standard risk

49 (62.8%)

17 (56.7%)

66 (61.1%)

High risk

29 (37.2%)

13 (43.3%)

42 (38.9%)

Treatment protocols

0.514

AALL0232

30 (38.5%)

14 (46.7%)

44 (40.7%)

AALL0331

48 (61.5%)

16 (53.3%)

64 (59.3%)

Molecular/cytogenetic studies

0.236

Favorable

66 (94.3%)

26 (86.7%)

92 (92.0%)

Unfavorable

4 (5.7%)

4 (13.3%)

8 (8.0%)

**Table 3.** Post-Consolidation MRD With Clinical and Biological Risk Factors (n = 27)
Parameters of interest	MRD (-)	MRD (+)	Total	P-value
CNS: central nervous system; MRD: minimal residual disease; WBC: white blood cell.
Gender				0.209
Male	8 (40.0%)	5 (71.4%)	13 (48.1%)
Female	12 (60.0%)	2 (28.6%)	14 (51.9%)
Age at diagnosis (years), median (range)	3.9 (1.5 - 13.9)	4.0 (2.1 - 11.0)	4.0 (1.5 - 13.9)	0.766
≤ 10 years	16 (80.0%)	6 (85.7%)	22 (81.5%)	1.000
> 10 years	4 (20.0%)	1 (14.3%)	5 (18.5%)
WBC at presentation (× 10⁹/L)	12.6 (1.1 - 331.3)	43.9 (3.0 - 395.8)	16.0 (1.1 - 395.8)	0.179
< 50 × 10⁹/L	16 (80.0%)	4 (57.1%)	20 (74.1%)	0.195
50 - 100 × 10⁹/L	1 (5.0%)	2 (28.6%)	3 (11.1%)
> 100 × 10⁹/L	3 (15.0%)	1 (14.3%)	4 (14.8%)
CNS status				0.156
CNS-1	19 (95.0%)	5 (71.4%)	24 (88.9%)
CNS-2	1 (5.0%)	1 (14.3%)	2 (7.4%)
CNS-3	None	1 (14.3%)	1 (3.7%)
Risk stratification				0.678
Standard risk	11 (55.0%)	3 (42.9%)	14 (51.9%)
High risk	9 (45.0%)	4 (57.1%)	13 (48.1%)
Treatment protocols				0.385
AALL0232	9 (45.0%)	5 (71.4%)	14 (51.9%)
AALL0331	11 (55.0%)	2 (28.6%)	13 (48.1%)
Post-induction treatment protocols				0.269
High risk	18 (90.0%)	5 (71.4%)	23 (85.2%)
Very high risk	1 (5.0%)	1 (14.3%)	2 (7.4%)
Salvage therapy	1 (5.0%)	1 (14.3%)	2 (7.4%)
Molecular/cytogenetic studies				1.000
Favorable	17 (85.0%)	6 (85.7%)	23 (85.2%)
Unfavorable	3 (15.0%)	1 (14.3%)	4 (14.8%)

Table 3. Post-Consolidation MRD With Clinical and Biological Risk Factors (n = 27)

Parameters of interest

MRD (-)

MRD (+)

Total

P-value

CNS: central nervous system; MRD: minimal residual disease; WBC: white blood cell.

Gender

0.209

Male

8 (40.0%)

5 (71.4%)

13 (48.1%)

Female

12 (60.0%)

2 (28.6%)

14 (51.9%)

Age at diagnosis (years), median (range)

3.9 (1.5 - 13.9)

4.0 (2.1 - 11.0)

4.0 (1.5 - 13.9)

0.766

≤ 10 years

16 (80.0%)

6 (85.7%)

22 (81.5%)

1.000

> 10 years

4 (20.0%)

1 (14.3%)

5 (18.5%)

WBC at presentation (× 10⁹/L)

12.6 (1.1 - 331.3)

43.9 (3.0 - 395.8)

16.0 (1.1 - 395.8)

0.179

< 50 × 10⁹/L

16 (80.0%)

4 (57.1%)

20 (74.1%)

0.195

50 - 100 × 10⁹/L

1 (5.0%)

2 (28.6%)

3 (11.1%)

> 100 × 10⁹/L

3 (15.0%)

1 (14.3%)

4 (14.8%)

CNS status

0.156

CNS-1

19 (95.0%)

5 (71.4%)

24 (88.9%)

CNS-2

1 (5.0%)

1 (14.3%)

2 (7.4%)

CNS-3

None

1 (14.3%)

1 (3.7%)

Risk stratification

0.678

Standard risk

11 (55.0%)

3 (42.9%)

14 (51.9%)

High risk

9 (45.0%)

4 (57.1%)

13 (48.1%)

Treatment protocols

0.385

AALL0232

9 (45.0%)

5 (71.4%)

14 (51.9%)

AALL0331

11 (55.0%)

2 (28.6%)

13 (48.1%)

Post-induction treatment protocols

0.269

High risk

18 (90.0%)

5 (71.4%)

23 (85.2%)

Very high risk

1 (5.0%)

1 (14.3%)

2 (7.4%)

Salvage therapy

1 (5.0%)

1 (14.3%)

2 (7.4%)

Molecular/cytogenetic studies

1.000

Favorable

17 (85.0%)

6 (85.7%)

23 (85.2%)

Unfavorable

3 (15.0%)

1 (14.3%)

4 (14.8%)

**Table 4.** Time and Site of Relapse
Chronology of relapse	n (%)	Time to relapse (months from diagnosis)
CNS: central nervous system; MRD: minimal residual disease.
Post-induction MRD (-)		16.1 (4.7 - 45.1)
Bone marrow	2/78 (2.6%)
Bone marrow + CNS	1/78 (1.3%)
CNS	1/78 (1.3%)
Post-induction MRD (+)
Post-consolidation MRD (-)		51.4 (15.3 - 76.3)
Bone marrow	3/20 (15.0%)
Bone marrow + CNS	1/20 (5.0%)
Post-consolidation MRD (+)		9.8 (7.7 - 11.9)
Bone marrow	1/7 (14.3%)
CNS	1/7 (14.3%)

Table 4. Time and Site of Relapse

Chronology of relapse

n (%)

Time to relapse (months from diagnosis)

CNS: central nervous system; MRD: minimal residual disease.

Post-induction MRD (-)

16.1 (4.7 - 45.1)

Bone marrow

2/78 (2.6%)

Bone marrow + CNS

1/78 (1.3%)

CNS

1/78 (1.3%)

Post-induction MRD (+)

Post-consolidation MRD (-)

51.4 (15.3 - 76.3)

Bone marrow

3/20 (15.0%)

Bone marrow + CNS

1/20 (5.0%)

Post-consolidation MRD (+)

9.8 (7.7 - 11.9)

Bone marrow

1/7 (14.3%)

CNS

1/7 (14.3%)

**Table 5.** Overall and Event-Free Survival
	Post-induction	Total (n = 108)	P-value	Post-consolidation	Total (n = 27)	P-value
MRD: minimal residual disease.
Mortality rate	4 (5.1%)	7 (23.3%)	11 (10.2%)	-	3 (15.0%)	4 (57.1%)	7 (25.9%)	-
Overall survival	94.7±2.6%	74.2±8.6%	89.2±3.1%	0.006	82.2±9.4%	42.9±18.7%	72.2±9.0%	0.014
Event-free survival	92.1±3.1%	61.1±10.2%	83.5±3.9%	0.001	65.5±11.9%	42.9±18.7%	58.3±10.6%	0.031

Table 5. Overall and Event-Free Survival

Post-induction

Total (n = 108)

P-value

Post-consolidation

Total (n = 27)

P-value

MRD (-) (n = 78)

MRD (+) (n = 30)

MRD (-) (n = 20)

MRD (+) (n = 7)

MRD: minimal residual disease.

Mortality rate

4 (5.1%)

7 (23.3%)

11 (10.2%)

3 (15.0%)

4 (57.1%)

7 (25.9%)

Overall survival

94.7±2.6%

74.2±8.6%

89.2±3.1%

0.006

82.2±9.4%

42.9±18.7%

72.2±9.0%

0.014

Event-free survival

92.1±3.1%

61.1±10.2%

83.5±3.9%

0.001

65.5±11.9%

42.9±18.7%

58.3±10.6%

0.031