Longer distance to specialized treatment centers does not adversely affect treatment intensity or outcomes in adult acute myeloid leukemia patients. A Danish national population-based cohort study

Figures & data

Figure 1 (A) Registries used to combine administrative, clinical, and outcome data. (B) Flowchart showing the selection of the study population.

Abbreviation: AML, acute myeloid leukemia.

Table 1 Patient characteristics according to distance to nearest specialized treatment center in 2,992 adult AML patients

	Distance to nearest specialized treatment center
	<10 km	10–25 km	25–50 km	50–100 km	>100 km
	n=726 (24.6%)	n=435 (14.5%)	n=612 (20.5%)	n=700 (23.4%)	n=519 (17.3%)
Patient characteristics, n
Sex, men (%)	380 (52,34)	247 (56.78)	343 (56.05)	399 (57.00)	283 (54.53)
Age, years, median (IQR)	69 (56–77)	68 (58–76)	69 (58–77)	68 (59–76)	68 (59–76)
Non-Western origin, n (%)	≤5 (≤1.0))	11 (1.6)	8 (1.3)	12 (2.8)	26 (3.6)
Socioeconomic indicators, n (%)
Income
Low (1st third)	205 (28.24)	120 (27.59)	210 (34.31)	254 (36.29)	209 (40.27)
Medium–low (2nd third)	233 (32.09)	145 (33.33)	212 (34.64)	236 (33.71)	171 (32.95)
High (3rd third)	288 (39.67)	170 (39.08)	190 (31.05)	210 (30.00)	139 (26.78)
Employment
Employed/self-employed	240 (33.06)	156 (35.86)	174 (28.43)	216 (30.86)	176 (33.91)
Unemployed/ leave	20 (2.75)	11 (2.53)	20 (3.27)	17 (2.43)	12 (2,31)
Anticipatory pension	90 (12,40)	53 (12.18)	86 (14.05)	96 (13.71)	69 (13.29)
Retirement pension	376 (51.79)	215 (49.43)	332 (54.25)	371 (53.00)	262 (50.48)
Education
Short	264 (36,36)	168 (38.62)	282 (46.08)	357 (51.00)	265 (51.06)
Medium	280 (38.57)	190 (43.68)	237 (38.73)	252 (36.00)	179 (34.49)
Longer	182 (25.07)	77 (17.70)	93 (15.20)	91 (13.00)	75 (14.45)
Cohabitation status
Living with someone	398 (54.82)	292 (67.13)	419 (68.46)	486 (69.43)	363 (69.94)
Living alone	328 (45.18)	143 (32.87)	193 (31.54)	214 (30.57)	156 (30.06)
Disease and treatment characteristics
Admission time (day 0–100), median (IQR)	41 (31–53)	36 (24–51)	42 (29–55)	45 (30–58)	47 (34–61)
Time to therapy, days, median (IQR)	3 (1–7)	4 (1–8)	3 (1–7)	4 (1–9)	4 (1–7)
Intent of treatment
Intensive treatment	374 (51.52)	234 (53.79)	319 (52.12)	379 (54.14)	282 (54.34)
Protocol participation, intensive therapy patients.
Yes	122 (32.62)	73 (31.20)	88 (27.59)	127 (33.51)	80 (28.37)
Comorbidities, score^a (%)
0	394 (59.07)	230 (57.64)	309 (57.12)	366 (56.74)	284 (59.17)
1	165 (24.74)	103 (25.81)	152 (28.10)	197 (30.54)	114 (23.75)
≥2^a	108 (16.20)	66 (16.54)	80 (14.79)	82 (12.71)	82 (17.08)
WHO PS, n (%)
0	205 (28.55)	130 (30.30)	182 (29.89)	171 (24.50)	114 (21.97)
1	297 (41.36)	172 (40.09)	245 (40.23)	312 (40.70)	241 (46.44)
≥2	216 (30.08)	127 (29.60)	182 (29.89)	215 (30.80)	164 (31.60)
tAML, n (%)	43 (5.92)	38 (8.74)	49 (8.01)	53 (7.57)	30 (5.78)
sAML, n (%)	145 (19.97)	95 (21.84)	122 (19.93)	152 (21.71)	94 (18.11)
Blast count marrow, %, median (IQR)	50 (30–75)	50 (30–78)	50 (30–74)	53 (35–72)	50 (30–74)
Blast count blood, %, median (IQR)	24 (4–60)	25 (5–61)	24 (5.5–52)	22 (4–53)	20 (4–59)
WBC, x10^9/L, median (IQR)	12.1 (2.5–54.8)	11.0 (2.4–47.3)	8.6 (2.2–42.9)	9.6 (2.2–45)	8.65 (2.3–43.5)
Platelet count, x10^9/L, median (IQR)	54 (27–104)	52 (30–103)	52 (27–100)	50 (25–96)	54 (28–110)
Extra-medullary AML, n (%)	54 (7.95)	40 (9.93)	53 (9.28)	58 (9.09)	42(9.09)
Cytogenetic risk group, MRC, n (%)
Favorable risk	21 (2.89)	18 (4.14)	17 (2.78)	25 (3.75)	17 (3.28)
Intermediate risk	394 (54.27)	206 (47.36)	337 (55.07)	399 (57.00)	293 (56.45)
Adverse risk	121 (16.67)	78 (17.93)	104 (16.99)	150 (21.43)	99 (19.08)
Karyotype, n (%)
Normal karyotype	237 (47.88)	129 (45.26)	209 (50.98)	252 (47.82)	192 (51.20)
Abnormal karyotype	258 (52.12)	156 (54.74)	201 (49.02)	275 (52.18)	183 (48.80)

Note: ^aAccording to the modified Charlson’s Comorbidity Index, which includes non-leukemia-related comorbidity.

Abbreviations: AML, acute myeloid leukemia; QR, interquartile range (25–75 centiles); HSCT, allogeneic stem cell transplantation; CR1, 1st complete remission; WHO PS, World Health Organization Performance Status; tAML, therapy-related AML; sAML, secondary AML; WBC, white blood count; MRC, Medical Research Council.

Table 2 Association between distances to nearest specialized treatment center and probability of intensive chemotherapy in 2,992 acute myeloid leukemia patients. Logistic regression analysis, crude, and adjusted estimates^a

All patients	Intensive chemotherapy, pts. (%)	Odds ratio, crude (95% CI)	Odds ratio, adjusted (95% CI)
Distance
<10 km	374 (51.5)	1.0	1.0
10–25 km	234 (53.7)	1.1 (0.9–1.4)	1.1 (0.7–1.7)
25–50 km	319 (52.1)	1.0 (0.8–1.3)	1.1 (0.7–1.7)
50–100 km	379 (54.1)	1.1 (0.9–1.4)	1.3 (0.9–2.0)
>100 km	282 (54.3)	1.1 (0.9–1.4)	1.4 (0.9–2.2)
Patients <65 years
Distance
<10 km	257 (89.2)	1.0	1.0
10–25 km	154 (89.5)	1.0 (0.6–1.9)	1.3 (0.5–3.3)
25–50 km	207 (88.5)	0.9 (0.5–1.6)	1.2 (0.5–2.8)
50–100 km	237 (89.8)	1.1 (0.6–1.8)	1.7 (0.7–4.1)
>100 km	187 (95.4)	2.5 (1.2–5.4)	7.5 (2.0–27.5)
Patients ≥65 years
Distance
<10 km	117 (26.7)	1.0	1.0
10–25 km	80 (30.4)	1.2 (0.9–1.7)	1.0 (0.6–1.8)
25–50 km	112 (29.6)	1.2 (0.9–1.6)	1.1 (0.7–1.9)
50–100 km	142 (32.6)	1.3 (1.0–1.8)	1.3 (0.8–2.1)
>100 km	95 (29.4)	1.1 (0.8–1.6)	1.0 (0.6–1.8)

Notes: ^aResults adjusted for age, sex, cohabitation, income, educational level, occupation, white blood cell count, cytogenetic risk group, WHO performance status, type of leukemia (de novo, secondary or therapy-related AML) and comorbidity.

Abbreviations: AML, acute myeloid leukemia; 95% CI, 95% confidence interval.

Figure 2 Association between distances to the nearest specialized treatment center and mortality. Results of all AML patients by age and by treatment intensity. Cox regression analysis, crude, and adjusted estimates.^a

Notes: Patients followed from time of diagnosis to death or end of follow-up. ^aResults adjusted for age, sex, cohabitation, income, educational level, occupation, white blood cell count, cytogenetic risk group, WHO performance status, type of leukemia (de novo, secondary, or therapy-related AML) and comorbidity.
Abbreviations: AML, acute myeloid leukemia; 95% CI, 95% confidence interval.

Table 3 Association between distances to nearest specialized treatment center and probability of CR in 1,463 AML patients treated with remission-induction therapy. Logistic regression analysis, crude, and adjusted estimates^a

All patients	CR, patients (%)	Odds ratio, crude (95% CI)	Odds ratio, adjusted (95% CI)
Distance
<10 km	252 (73.0)	1.0	1.0
10–25 km	147 (68.4)	0.8 (0.5–1.2)	1.1 (0.8–1.6)
25–50 km	200 (68.7)	0.8 (0.6–1.1)	1.0 (0.7–1.4)
50–100 km	251 (71.9)	0.9 (0.7–1.3)	1.1 (0.8–1.6)
>100 km	195 (74.1)	1.1 (0.7–1.5)	1.3 (0.9–1.9)
Patients <65 years
Distance
<10 km	187 (77.0)	1.0	1.0
10–25 km	104 (71.2)	0.7 (0.5–1.2)	0.8 (0.42–1.33)
25–50 km	141 (72.7)	0.8 (0.5–1.2)	0.9 (0.49–1.45)
50–100 km	168 (77.8)	1.0 (0.7–1.6)	1.1 (0.65–1.88)
>100 km	139 (79.4)	1.2 (0.7–1.9)	1.2 (0.65–2.08)
Patients ≥65 years
Distance
<10 km	65 (63.7)	1.0	1.0
10–25 km	43 (62.3)	0.9 (0.5–1.8)	1.3 (0.6–2.7)
25–50 km	59 (60.8)	0.9 (0.5–1.6)	1.0 (0.5–1.9)
50–100 km	83 (62.4)	0.9 (0.6–1.6)	1.1 (0.6–2.0)
>100 km	56 (63.6)	1.0 (0.6–1.8)	0.9 (0.5–1.9)

Notes: ^aResults adjusted for age, sex, cohabitation, income, educational level, occupation, white blood cell count, cytogenetic risk group, WHO performance status, type of leukemia (de novo, secondary or therapy-related AML) and comorbidity.

Abbreviations: AML, acute myeloid leukemia; 95% CI, 95% confidence interval; CR, complete remission.

Figure 3 Crude survival according to categorical distance to the nearest specialized treatment center. Overall survival in all patients (A), in patients <65 years (B), in all patients ≥65 years (C), in all patients receiving intensive chemotherapy (D), and in all patients receiving intensive chemotherapy surviving to achieve a CR (E).

Abbreviations: AML, acute myeloid leukemia; CR, complete remission.