Factors associated with risk and prognosis of intensive care unit admission in patients with acute leukemia: a Danish nationwide cohort study

Figures & data

Table 1. Characteristics of 1417 AML and 306 ALL patients overall and by ICU admission in the matched cohort.

	AML patients			ALL patients
	All AML patients (N = 1417)	ICU within 3 years of diagnosis (N = 397)	Matched cohort (N = 397)	All patients (N = 306)	ICU within 3 years of diagnosis (N = 80)	Matched cohort (N = 80)
Patient characteristics
Age
Median (IQR), years	61 (50–68)	59 (50–67)	59 (49–67)	43 (25–61)	45 (26–60)	44.5 (28–60)
Sex
Male no. (%)	766 (54.1)	230 (57.9)	230 (57.9)	115 (37.6)	46 (57.5)	46 (57.0)
Number of comorbidities, no. (%)
0	375 (26.5)	102 (25.7)	108 (27.2)	72 (23.5)	20 (25.0)	22 (27.5)
1	744 (52.5)	213 (56.7)	191 (48.1)	171 (55.9)	43 (53.7)	43 (53.8)
≥2	298 (21.0)	82 (20.6)	98 (24.7)	63 (20.6)	17 (21.3)	15 (18.8)
WHO performance status, no. (%)
0	614 (43.3)	158 (39.8)	170 (42.8)	136 (44.4)	35 (43.8)	40 (50.0)
1	614 (43.3)	167 (42.1)	193 (48.6)	145 (47.4)	35 (43.8)	<40 (<50)
≥2	189 (13.4)	72 (18.1)	34 (8.6)	25 (8.2)	10 (12.5)	<5 (<6)
Disease characteristics at diagnosis
Time to treatment
Median (IQR), days	3 (1–7)	3 (1–8)	3 (1–8)	3 (1–5)	2 (1–5)	2.5 (1–5)
Blast count
Blood, median % (IQR)	25 (5–60)	25 (5–64)	23.5 (5–55)	48 (14–77)	50 (12–80)	38.5 (16–76)
Bone marrow, median % (IQR)	50 (30–79)	55 (31–78)	50 (30.5–76)	84 (66–91)	82 (70–90)	85 (75–94)
White blood cells count (WBC)
Median (IQR) × 10^^9/L	9.75 (2.2–41.0)	9.40 (2.10–47.2)	6.92 (2.10–34.9)	10.8 (3.4–45.6)	18.00 (4.3–54.7)	9.50 (4.1–38.4)
WBC ≥ 100 × 10^^9/L, no. (%)	168 (11.9)	57 (14.4)	35 (8.8)	43 (14.1)	17 (21.3)	7 (8.8)
Platelet count
Median (IQR) × 10^^9/L	56 (31–102)	56.5 (31–95)	59 (32–105)	55 (28–118.5)	57 (28–119)	55 (32–108)
Lactate dehydrogenase (LDH)
Median (IQR) × 10^^9/L	359 (228–622)	382 (226–697)	343 (219–557)	575 (301–1262)	761 (346–1806)	548 (337–894)
Cytogenetic risk group, no. (%)
Good/favorable	81 (5.7)	24 (6.0)	29 (7.3)
Intermediate	916 (64.6)	248 (62.5)	264 (66.5)
Advanced/complex	266 (18.8)	83 (20.9)	61 (15.4)
Missing	154 (10.9)	42 (10.6)	43 (10.8)
Phenotype
B-ALL, no. (%)				243 (79.4)	63 (78.8)	67 (83.7)
T-ALL, no. (%)				63 (20.6)	17 (21.3)	13 (16.3)
Events during follow-up
Complete remission (CR)
No. of pts. (%)	970 (68.5)	247 (62.2)	296 (75.6)	221 (72.2)	50 (62.5)	65 (81.3)
Relapse
No. of pts. (%) total	415 (29.3)	97 (24.4)	130 (32.75)	39 (12.7)	7 (8.8)	16 (20.0)
No. of pts. relapsed before first ICU admission or index date (%)	–	32 (8.3)	18 (4.5)	–	0 (0)	0 (0)
Allogeneic HCST
No. of pts. (%) total	290 (20.5)	83 (20.9)	88 (22.2)	82 (26.8)	22 (27.5)	18 (22.5)
No. of pts. transplanted before first ICU admission or index date (%)	–	58 (14.1)	32 (8.1)	–	12 (15.0)	9 (11.3)

Figure 1. Prevalence of first time ICU admissions by treatment course for AML and ALL patients. Timing of first time ICU admission according to diagnosis and initiation of treatment cycle 1, 2, and 3 or consolidation for AML and ALL patients.

Figure 2. Kaplan Meier curves of ICU admission risk and survival. Proportion of patients with ICU admission by time according to WHO PS for AML (A) and ALL (B) and according to number of comorbidities for AML (C) and ALL (D). Crude survival from index date by ICU status for AML (E) and ALL patients (F).

Table 2. Potential risk factors for ICU admission in 1417 AML and 306 ALL patients.

Potential risk factors of ICU admission in AL patients
	Within 3 years of AML diagnosis			Within 3 years of ALL diagnosis
	Proportion (%) of ICU-admitted patients (95% CI)	Crude RR (95% CI)	Adjusted RR* (95% CI)	Proportion (%) of ICU-admitted patients (95% CI)	Crude RR (95% CI)	Adjusted RR** (95% CI)
Age
15–40	28.2 (21.5–34.8)	1.00	1.00	22.1 (15.3–28.8)	1.00	1.00
41–50	27.6 (21.3–33.9)	0.97 (0.70–1.36)	0.98 (0.70–1.37)	42.1 (26.3–57.9)	1.90 (1.18–3.08)	1.86 (1.08–3.19)
51–60	33.8 (28.8–38.9)	1.20 (0.90–1.59)	1.16 (0.86–1.55)	28.3 (15.2–41.3)	1.26 (0.73–2.20)	1.04 (0.51–2.11)
>60	25.4 (22.2–28.6)	0.90 (0.69–1.17)	0.84 (0.63–1.11)	24.7 (15.0–34.3)	1.11 (0.68–1.81)	1.05 (0.63–1.74)
Sex
Male	30.0 (26.8–33.3)	1.17 (0.99–1.39)	1.18 (0.99–1.40)	24.1 (18.0–30.2)	0.82 (0.56–1.19)	0.90 (0.56–1.48)
Number of comorbidities
0	27.2 (22.7–31.7)	1.00	1.00	27.8 (17.3–38.2)	1.00	1.00
1	28.6 (25.4–31.9)	1.05 (0.86–1.28)	1.09 (0.88–1.34)	25.1 (18.6–31.7)	0.92 (0.58–1.44)	0.90 (0.55–1.45)
>1	27.5 (22.4–21.6)	1.01 (0.79–1.29)	1.07 (0.81–1.40)	27.0 (15.9–38.1)	0.97 (0.56–1.67)	0.94 (0.51–1.75)
PS at diagnosis
0	25.7 (22.3–29.2)	1.00	1.00	25.7 (18.4–33.1)	1.00	1.00
1	27.1 (23.7–30.7)	1.06 (0.86–1.27)	1.05 (0.87–1.27)	24.1 (17.1–31.1)	0.94 (0.63–1.41)	0.90 (0.55–1.48)
>1	38.1 (31.2–45.0)	1.48 (1.18–1.85)	1.50 (1.19–1.90)	40.0 (20.7–59.3)	1.52 (0.88–2.70)	1.62 (0.88–2.99)
Cytogenetik risk group
Favourable	27.2 (24.5–30.0)	0.97 (0.68–1.38)	0.92 (0.0.63–1.33)
Intermediate	26.5 (17.7–35.4)	1.00	1.00
Complex/advanced	31.1 (25.8–36.6)	1.14 (0.93–1.40)	1.15 (0.93–1.42)
Type of AML
De novo	27.9 (25.2–30.5)	1.00	1.00
s-AML	30.2 (24.0–36.5)	1.08 (0.86–1.36)	1.03 (0.80–1.32)
t-AML	25.2 (17.1–33.3)	0.91 (0.65–1.27)	0.87 (0.61–1.23)
Philadelphia chromosome
Negative				25.4 (20.0–30.8)	1.00	1.00
Positive				30.0 (17.1–42.9)	1.17 (0.73–1.88)	1.07 (0.61–1.87)

Crude and adjusted relative risk (RR).

PS: performance status; s-AML: secondary AML; t-AML: therapy-related AML.

*Adjusted for age, sex, number of comorbidities, WHO performance status, MRC cytogenetic risk group, secondary AML, and year of diagnosis. Death was considered a competing risk.

**Adjusted for age, sex, WHO Performance status, number of comorbidities, year of diagnosis, ALL phenotype, and Philadelphia chromosome status.

Table 3. Mortality after ICU admission in AML and ALL patients.

	AML patients cumulative mortality				ALL patients cumulative mortality
	Proportion % (95% CI)		RR (95% CI)		Proportion % (95% CI)		RR (95% CI)
Years since ICU-admission	ICU-admitted patients	Matched cohort	Crude	Adjusted*	ICU-admitted patients	Matched cohort	Crude	Adjusted**
1 year	69.7 (65.2–74.2)	35.0 (30.5–40.0)	2.77 (2.25–3.43)	2.74 (2.17–3.47)	65.0 (54.6–75.2)	20.0 (12.8–30.6)	2.77 (1.72–4.47)	3.04 (1.54–6.02)
3 years	82.5 (78.5–86.2)	56.4 (51.5–61.5)	2.11 (1.76–2.54)	2.21 (1.75–2.79)	70.3 (60.1–80.0)	37.5 (27.2–51.4)	1.96 (1.27–3.02)	2.04 (1.19–3.52)
5 years	83.5 (79.5–87.1)	64.3 (59.3–69.3)	1.74 (1.45–2.10)	1.80 (1.42–2.30)	71.7 (61.5–81.2)	41.2 (30.9–53.4)	1.97 (1.27–3.06)	2.09 (1.19–3.67)
0–30 days			15.54 (8.81–27.40)	12.66 (6.75–23.74)			9.33 (2.95 − 29.57)	13.37 (3.13–57.09)
30 days–1 year			1.31 (1.06–1.61)	1.28 (1.06–1.54)			1.63 (1.04–2.57)	1.59 (0.87–2.88)
1–3 years			1.27 (0.96–1.70)	1.31 (0.98–1.74)			0.69 (0.23–2.09)	3.49 (0.22–54.31)
1–5 years			1.00 (0.78–1.29)	0.98 (0.76–1.26)			0.81 (0.30–2.23)	N/A

Crude and adjusted relative risk (RR) of death.

*Adjusted for WHO Performance status, year of diagnosis, MRC cytogenetic risk group, number of comorbidities, and type of AML.

**Adjusted for WHO Performance status, number of comorbidities, year of diagnosis, ALL phenotype, and Philadelphia chromosome status.

Table 4. Mortality after dialysis or mechanical ventilation in the ICU for AML and ALL patients.

	AML patients				ALL patients
	Mortality after dialysis RR (95% CI)		Mortality after mechanical ventilation RR (95% CI)		Mortality after dialysis RR (95% CI)		Mortality after mechanical ventilation RR (95% CI)
Years since ICU-admission	Crude	Adjusted*	Crude	Adjusted*	Crude	Adjusted**	Crude	Adjusted**
1 year	7.13 (4.90–10.39)	5.35 (3.63–7.89)	5.32 (4.34–6.51)	5.64 (4.26–7.47)	9.79 (3.05–31.42)	5.39 (4.26–6.81)	13.43 (7.21–25.01)	11.00 (3.51–34.47)
3 years	4.03 (2.79–5.82)	3.84 (2.44–6.04)	3.13 (2.57–3.80)	3.17 (2.38–4.24)	3.21 (1.22–8.47)	3.01 (2.41–3.77)	6.86 (3.89–12.09)	7.08 (2.37–21.19)
5 years	3.36 (2.35–4.81)	3.16 (2.04–4.91)	2.52 (2.07–3.07)	2.64 (1.95–3.58)	2.87 (1.16–7.12)	2.52 (2.00–3.17)	5.15 (2.94–9.02)	5.68 (1.85–17.42)

Crude and adjusted relative risk (RR) of death.

*Adjusted for WHO Performance status, year of diagnosis, and number of comorbidities.

**Adjusted for WHO Performance status, year of diagnosis, ALL phenotype, and Philadelphia chromosome status.