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, July 2025, pages 000-000

Does Time Matter From Diagnosis to Induction in Acute Myeloid Leukemia?

Figure 1. Kaplan-Meier estimates of overall survival according TDT. TDT: timing from diagnosis to treatment.

Figure 2. Forest plot of adjusted hazard ratios and 95% confidence interval for each predictor.

**Table 1.** Descriptive Characteristics of Patients and Comparison of TDT
Characteristics	1 to 5 days (n = 130)	6 to 10 days (n = 30)	11+ days (n = 27)	P-values	Total
*Statistical significance (P < 0.05). AML: acute myeloid leukemia; ANC: absolute neutrophil count; ELN: European LeukemiaNet; Hb: hemoglobin; NS: not statistically significant; SD: standard deviation; TDT: timing from diagnosis to treatment; WBC: white blood cell.
Age (years), mean (SD)	61.9 (16.3)	63.3 (15.0)	71.2 (11.3)
Age (years), n (%)
Under 60 years	53 (40.8%)	9 (30.0%)	2 (7.4%)	< 0.05*	64
60+ years	77 (59.2%)	21 (70.0%)	25 (92.6%)		123
Sex, n (%)
Male	63 (48.5%)	15 (50.0%)	16 (59.3%)	NS	94
Female	67 (51.5%)	15 (50.0%)	11 (40.7%)		93
Race, n (%)
White	106 (92.2%)	24 (88.9%)	24 (88.9%)	NS	154
Black	4 (3.5%)	2 (7.4%)	1 (3.7%)		7
Asian	2 (1.7%)	0 (0%)	0 (0%)		2
Other	3 (2.6%)	1 (3.7%)	2 (7.4%)		6
Lab parameters at diagnosis, median (range)
WBC (× 10³/µL)	20.2 (0.4 - 397.8)	4.4 (0.5 - 98.4)	3.3 (0.4 - 800.0)	NS
ANC (µL)	1125 (0 - 51,700)	380 (0 - 5,490)	600 (1 - 7,230)
Hb (g/dL)	8.3 (3.4 - 14.8)	8.7 (4.4 - 13.8)	8.1 (5.3 - 13.7)
Platelets (× 10³/µL)	56 (5 - 367)	52 (5 - 633)	69 (16 - 538)
Peripheral blood blast (%)	38.0% (0 - 99.0)	5.5% (0 - 92.5)	4.5% (0 - 86)
Bone marrow blasts (%)	56.4% (0 - 99.0)	31.4% (1.5 - 96.2)	30.2% (7.0 - 80.0)
WBC > 50 (× 10³/µL)	43	5	2
ELN 2022 risk stratification
Favorable	28 (22.8%)	6 (20.7%)	3 (11.5%)	0.305	37
Intermediate	50 (40.7%)	8 (27.6%)	9 (34.6%)		67
Adverse	45 (36.6%)	15 (51.7%)	14 (53.9%)		74
Secondary AML status
De novo	96 (71.6%)	22 (16.4%)	16 (11.9%)		134
Mutations at diagnosis				NS
CBF	6 (4.8%)	4 (13.3%)	1 (4.0%)		11
NPM1	49 (38.0%)	6 (20.0%)	3 (11.1%)		58
CEBPA	9 (7.0%)	3 (10.0%)	1 (3.7%)		13
FLT3-ITD	34 (26.4%)	2 (6.7%)	1 (3.7%)		37
FLT3-TKI	4 (3.1%)	1 (3.3%)	1 (3.7%)		6
KMT2A	2 (1.6%)	0 (0%)	0 (0%)		2
TP53	7 (5.4%)	4 (13.3%)	4 (15.4%)		15

Table 1. Descriptive Characteristics of Patients and Comparison of TDT

Characteristics

1 to 5 days (n = 130)

6 to 10 days (n = 30)

11+ days (n = 27)

P-values

Total

*Statistical significance (P < 0.05). AML: acute myeloid leukemia; ANC: absolute neutrophil count; ELN: European LeukemiaNet; Hb: hemoglobin; NS: not statistically significant; SD: standard deviation; TDT: timing from diagnosis to treatment; WBC: white blood cell.

Age (years), mean (SD)

61.9 (16.3)

63.3 (15.0)

71.2 (11.3)

Age (years), n (%)

Under 60 years

53 (40.8%)

9 (30.0%)

2 (7.4%)

< 0.05*

60+ years

77 (59.2%)

21 (70.0%)

25 (92.6%)

123

Sex, n (%)

Male

63 (48.5%)

15 (50.0%)

16 (59.3%)

Female

67 (51.5%)

15 (50.0%)

11 (40.7%)

Race, n (%)

White

106 (92.2%)

24 (88.9%)

154

Black

4 (3.5%)

2 (7.4%)

1 (3.7%)

Asian

2 (1.7%)

0 (0%)

Other

3 (2.6%)

1 (3.7%)

2 (7.4%)

Lab parameters at diagnosis, median (range)

WBC (× 10³/µL)

20.2 (0.4 - 397.8)

4.4 (0.5 - 98.4)

3.3 (0.4 - 800.0)

ANC (µL)

1125 (0 - 51,700)

380 (0 - 5,490)

600 (1 - 7,230)

Hb (g/dL)

8.3 (3.4 - 14.8)

8.7 (4.4 - 13.8)

8.1 (5.3 - 13.7)

Platelets (× 10³/µL)

56 (5 - 367)

52 (5 - 633)

69 (16 - 538)

Peripheral blood blast (%)

38.0% (0 - 99.0)

5.5% (0 - 92.5)

4.5% (0 - 86)

Bone marrow blasts (%)

56.4% (0 - 99.0)

31.4% (1.5 - 96.2)

30.2% (7.0 - 80.0)

WBC > 50 (× 10³/µL)

ELN 2022 risk stratification

Favorable

28 (22.8%)

6 (20.7%)

3 (11.5%)

0.305

Intermediate

50 (40.7%)

8 (27.6%)

9 (34.6%)

Adverse

45 (36.6%)

15 (51.7%)

14 (53.9%)

Secondary AML status

De novo

96 (71.6%)

22 (16.4%)

16 (11.9%)

134

Mutations at diagnosis

CBF

6 (4.8%)

4 (13.3%)

1 (4.0%)

NPM1

49 (38.0%)

6 (20.0%)

3 (11.1%)

CEBPA

9 (7.0%)

3 (10.0%)

1 (3.7%)

FLT3-ITD

34 (26.4%)

2 (6.7%)

1 (3.7%)

FLT3-TKI

4 (3.1%)

1 (3.3%)

1 (3.7%)

KMT2A

2 (1.6%)

0 (0%)

TP53

7 (5.4%)

4 (13.3%)

4 (15.4%)

**Table 2.** Overall Survival in Months by Time to Induction for All Patients
Time to induction	Mean (SD)
SD: standard deviation.
1 to 5 days (n = 130)	20.5 (26.6)
6 to 10 days (n = 30)	18.0 (21.4)
11+ days (n = 27)	10.4 (11.2)

Table 2. Overall Survival in Months by Time to Induction for All Patients

Time to induction

Mean (SD)

SD: standard deviation.

1 to 5 days (n = 130)

20.5 (26.6)

6 to 10 days (n = 30)

18.0 (21.4)

11+ days (n = 27)

10.4 (11.2)

**Table 3.** HR for Overall Survival vs. Time to Induction
Time to induction	HR	95% CI
CI: confidence interval; HR: hazard ratio.
1 to 5 days vs. 11+ days	0.567	0.325 - 0.989
1 to 5 days vs. 6 to 10 days	1.072	0.577 - 1.992
11+ days vs. 6 to 10 days	1.780	0.839 - 3.773

Table 3. HR for Overall Survival vs. Time to Induction

Time to induction

95% CI

CI: confidence interval; HR: hazard ratio.

1 to 5 days vs. 11+ days

0.567

0.325 - 0.989

1 to 5 days vs. 6 to 10 days

1.072

0.577 - 1.992

11+ days vs. 6 to 10 days

1.780

0.839 - 3.773

**Table 4.** Reasons for Delay in Initiating Chemotherapy 11+ Days After Diagnosis
Reasons for delay	n = 27 (%)
NGS: next-generation sequencing.
Waiting for NGS/molecular results	11 (41%)
Active infection or hemodynamic instability	7 (26%)
Waiting for patient’s decision regarding treatment	7 (26%)
No clear reason identified	2 (7%)

Table 4. Reasons for Delay in Initiating Chemotherapy 11+ Days After Diagnosis

Reasons for delay

n = 27 (%)

NGS: next-generation sequencing.

Waiting for NGS/molecular results

11 (41%)

Active infection or hemodynamic instability

7 (26%)

Waiting for patient’s decision regarding treatment

7 (26%)

No clear reason identified

2 (7%)

**Table 5.** aORs for Overall Survival vs. Predictors
Predictors	aHR	95% CI
aHR: adjusted hazard ratio; CI: confidence interval; ELN: European LeukemiaNet.
Time to induction
11+ days vs. 6 - 10 days	1.398	0.624 - 3.223
1 - 5 days vs. 6 - 10 days	1.390	0.740 - 2.853
1 - 5 days vs. 11+ days	0.994	0.546 - 1.904
Chemotherapy intensity
Intensive vs. non-intensive	0.627	0.370 - 1.056
Age
< 60 years vs. ≥ 60 years	0.634	0.347 - 1.124
Year of diagnosis
2020 forward vs. before 2015	0.395	0.203 - 0.802
2015 to 2020 vs. before 2015	0.852	0.455 - 1.674
2015 to 2020 vs. 2020 forward	2.157	1.311 - 3.575
ELN status
Intermediate vs. adverse	0.514	0.314 - 0.829
Favorable vs. adverse	0.144	0.054 - 0.319
Favorable vs. intermediate	0.279	0.103 - 0.642

Table 5. aORs for Overall Survival vs. Predictors

Predictors

aHR

95% CI

aHR: adjusted hazard ratio; CI: confidence interval; ELN: European LeukemiaNet.

Time to induction

11+ days vs. 6 - 10 days

1.398

0.624 - 3.223

1 - 5 days vs. 6 - 10 days

1.390

0.740 - 2.853

1 - 5 days vs. 11+ days

0.994

0.546 - 1.904

Chemotherapy intensity

Intensive vs. non-intensive

0.627

0.370 - 1.056

Age

< 60 years vs. ≥ 60 years

0.634

0.347 - 1.124

Year of diagnosis

2020 forward vs. before 2015

0.395

0.203 - 0.802

2015 to 2020 vs. before 2015

0.852

0.455 - 1.674

2015 to 2020 vs. 2020 forward

2.157

1.311 - 3.575

ELN status

Intermediate vs. adverse

0.514

0.314 - 0.829

Favorable vs. adverse

0.144

0.054 - 0.319

Favorable vs. intermediate

0.279

0.103 - 0.642

**Table 6.** Early Death by Time to Induction for AML
Early death	1 to 5 days	6 to 10 days	11+ days	Total
AML: acute myeloid leukemia.
Death after 90 days	43 (66.2%)	9 (13.9%)	13 (20.0%)	65
Death within 30 days	13 (100%)	0 (0%)	0 (0%)	13
Death within 90 days	6 (50.0%)	3 (25.0%)	3 (25.0%)	12

Table 6. Early Death by Time to Induction for AML

Early death

1 to 5 days

6 to 10 days

11+ days

Total

AML: acute myeloid leukemia.

Death after 90 days

43 (66.2%)

9 (13.9%)

13 (20.0%)

Death within 30 days

13 (100%)

0 (0%)

Death within 90 days

6 (50.0%)

3 (25.0%)

**Table 7.** Clinical Outcomes Based on TDT Groups
Characteristics	1 to 5 days (n = 130)	6 to 10 days (n = 30)	11+ days (n = 27)	P-values^a	Total
*Statistical significance (P < 0.05). ^aFisher’s exact test was used for platelet recovery days due to low sample size. SD: standard deviation; TDT: timing from diagnosis to treatment.
Time to best response (days), mean (SD)	35.3 (10.5)	35.5 (10.2)	34.3 (11.4)
Chemotherapy intensity, n (%)
Non-intensive	38 (29.2%)	14 (46.7%)	19 (70.4%)	P < 0.05*	71
Intensive	92 (70.8%)	16 (53.3%)	8 (29.6%)		116
Remission status, n (%)
Complete remission	90 (72.6%)	21 (75.0%)	10 (45.5%)	P < 0.05*	121
No response	34 (27.4%)	7 (25.0%)	12 (54.6%)		53
Platelet recovery (days), mean (SD)	27.4 (20.9)	25.3 (10.1)	27.4 (23.3)
Platelet recovery, n (%)
1 to 28 days	84 (67.2%)	18 (64.3%)	11 (50.0%)	0.481^a	113
29+ days	24 (19.2%)	6 (21.4%)	5 (22.73%)		35
No recovery	17 (13.6%)	4 (14.3%)	6 (27.3%)		27
Neutrophil recovery (days), mean (SD)	30.8 (14.6)	29.7 (10.5)	26.7 (14.1)
Neutrophil recovery
No recovery	22 (18.2%)	4 (14.3%)	6 (33.3%)	0.242	32
Recovery	99 (81.8%)	24 (85.7%)	12 (66.7%)		135
Transplant
No transplant	59 (63.4%)	19 (20.4%)	15 (16.1%)		No transplant
Allogeneic stem cell transplant	40 (75%)	7 (13%)	6 (11%)		Allogeneic stem cell transplant

Table 7. Clinical Outcomes Based on TDT Groups

Characteristics

1 to 5 days (n = 130)

6 to 10 days (n = 30)

11+ days (n = 27)

P-values^a

Total

*Statistical significance (P < 0.05). ^aFisher’s exact test was used for platelet recovery days due to low sample size. SD: standard deviation; TDT: timing from diagnosis to treatment.

Time to best response (days), mean (SD)

35.3 (10.5)

35.5 (10.2)

34.3 (11.4)

Chemotherapy intensity, n (%)

Non-intensive

38 (29.2%)

14 (46.7%)

19 (70.4%)

P < 0.05*

Intensive

92 (70.8%)

16 (53.3%)

8 (29.6%)

116

Remission status, n (%)

Complete remission

90 (72.6%)

21 (75.0%)

10 (45.5%)

P < 0.05*

121

No response

34 (27.4%)

7 (25.0%)

12 (54.6%)

Platelet recovery (days), mean (SD)

27.4 (20.9)

25.3 (10.1)

27.4 (23.3)

Platelet recovery, n (%)

1 to 28 days

84 (67.2%)

18 (64.3%)

11 (50.0%)

0.481^a

113

29+ days

24 (19.2%)

6 (21.4%)

5 (22.73%)

No recovery

17 (13.6%)

4 (14.3%)

6 (27.3%)

Neutrophil recovery (days), mean (SD)

30.8 (14.6)

29.7 (10.5)

26.7 (14.1)

Neutrophil recovery

No recovery

22 (18.2%)

4 (14.3%)

6 (33.3%)

0.242

Recovery

99 (81.8%)

24 (85.7%)

12 (66.7%)

135

Transplant

No transplant

59 (63.4%)

19 (20.4%)

15 (16.1%)

No transplant

Allogeneic stem cell transplant

40 (75%)

7 (13%)

6 (11%)

Allogeneic stem cell transplant