J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 16, Number 12, December 2024, pages 625-634

Higher Processed Blood Volume of Granulocyte and Monocyte Adsorption Apheresis Ameliorates Long-Term Disease Activity in Ulcerative Colitis Patients

Figure 1. Flow diagram of the present study. GMA: granulocyte and monocyte adsorption apheresis; UC: ulcerative colitis.

Figure 2. Kaplan-Meier analysis for UC exacerbation within 1 year after GMA. GMA: granulocyte and monocyte adsorption apheresis; UC: ulcerative colitis.

Figure 3. Comparison of groups divided by scheduled treatment time (a) and GMA dose (b). GMA: granulocyte and monocyte adsorption apheresis.

**Table 1.** Patient Characteristics and Comparisons Between Groups Divided by GMA Dose
Variable	All (N = 72)	Lower GMA dose (N = 36)	Higher GMA dose (N = 36)	P
Continuous data are presented as median (IQR). *Analysis of administered cases only. Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte apheresis; Hb: hemoglobin; IQR: interquartile range; 6-MP: 6-mercaptopurine; PSL: prednisolone; UC: ulcerative colitis; WBC: white blood cell count.
Age, years	44.4 (28.7 - 54.3)	43.4 (34.1 - 56.5)	44.4 (28.0 - 53.2)	0.68
Male gender, n (%)	47 (65%)	29 (81%)	18 (50%)	0.01
Body weight, kg	56.9 (51.1 - 63.9)	63.0 (57.8 - 68.7)	51.0 (47.8 - 54.0)	< 0.01
Duration of UC, years	5.3 (2.2 - 12.2)	3.6 (1.6 - 17.4)	6.5 (3.3 - 10.5)	0.60
Extend of UC lesion (total/hemi-sided)	49/23	26/10	23/13	0.61
Clinical severity (mild/moderate/severe), n	6/57/9	3/28/5	3/29/4	0.94
Seo index (mild/moderate/severe), n	20/41/11	12/19/5	8/22/6	0.57
Seo index score	178 (147 - 205)	168 (140 - 212)	183 (154 - 202)	0.38
Comorbidities
Diabetes, n (%)	6 (8%)	4 (11%)	2 (6%)	0.67
Hypertension, n (%)	12 (17%)	6 (17%)	6 (17%)	1.0
Dyslipidemia, n (%)	4 (6%)	3 (8%)	1 (3%)	0.61
Chronic kidney disease, n (%)	6 (8%)	3 (8%)	3 (8%)	1.0
Current smoking, n (%)	14 (19%)	6 (17%)	8 (22%)	0.77
Alcohol drinking, n (%)	11 (15%)	8 (22%)	3 (8%)	0.19
WBC, × 10³/µL	9.8 (7.5 - 13.0)	9.7 (7.8 - 12.7)	10.0 (7.3 - 13.5)	0.91
Hb, g/dL	11.9 (10.9 - 12.8)	12.7 (11.8 - 13.5)	11.2 (10.6 - 12.1)	< 0.01
Alb, g/dL	3.3 (2.9 - 3.7)	3.3 (2.9 - 3.7)	3.4 (2.7 - 3.7)	0.68
CRP, mg/dL	1.17 (0.29 - 3.26)	1.46 (0.38 - 3.30)	0.89 (0.27 - 3.24)	0.50
ESR, mm/h	35 (19 - 48)	32 (17 - 43)	38 (22 - 49)	0.28
Medications at GMA initiation, n (%)
5-ASA	65 (90%)	32 (89%)	33 (92%)	1.0
AZA or 6-MP	8 (11%)	4 (11%)	4 (11%)	1.0
PSL	57 (79%)	30 (83%)	27 (75%)	0.56
5-ASA dose, mg/day*	4,000 (3,600 - 4,800)	3,800 (3,600 - 4,000)	4,000 (3,600 - 4,800)	0.07
AZA or 6-MP dose, mg/kg/day*	0.95 (0.66, 1.18)	0.66 (0.60, 0.93)	0.98 (0.96 - 1.23)	0.15
Biologics within 1-year after GMA, n (%)	34 (47%)	15 (42%)	19 (53%)	0.48
GMA dose, mL/kg/session	34.2 (28.6 - 39.2)	28.6 (26.6 - 31.6)	39.3 (36.4 - 47.5)	< 0.01
GMA session treatment time (60 min/> 60 min), n	54/18	35/1	19/17	< 0.01
UC exacerbation within 1-year after GMA, n (%)	34 (47%)	23 (64%)	11 (31%)	< 0.01

Table 1. Patient Characteristics and Comparisons Between Groups Divided by GMA Dose

Variable

All (N = 72)

Lower GMA dose (N = 36)

Higher GMA dose (N = 36)

Continuous data are presented as median (IQR). *Analysis of administered cases only. Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte apheresis; Hb: hemoglobin; IQR: interquartile range; 6-MP: 6-mercaptopurine; PSL: prednisolone; UC: ulcerative colitis; WBC: white blood cell count.

Age, years

44.4 (28.7 - 54.3)

43.4 (34.1 - 56.5)

44.4 (28.0 - 53.2)

0.68

Male gender, n (%)

47 (65%)

29 (81%)

18 (50%)

0.01

Body weight, kg

56.9 (51.1 - 63.9)

63.0 (57.8 - 68.7)

51.0 (47.8 - 54.0)

< 0.01

Duration of UC, years

5.3 (2.2 - 12.2)

3.6 (1.6 - 17.4)

6.5 (3.3 - 10.5)

0.60

Extend of UC lesion (total/hemi-sided)

49/23

26/10

23/13

0.61

Clinical severity (mild/moderate/severe), n

6/57/9

3/28/5

3/29/4

0.94

Seo index (mild/moderate/severe), n

20/41/11

12/19/5

8/22/6

0.57

Seo index score

178 (147 - 205)

168 (140 - 212)

183 (154 - 202)

0.38

Comorbidities

Diabetes, n (%)

6 (8%)

4 (11%)

2 (6%)

0.67

Hypertension, n (%)

12 (17%)

6 (17%)

1.0

Dyslipidemia, n (%)

4 (6%)

3 (8%)

1 (3%)

0.61

Chronic kidney disease, n (%)

6 (8%)

3 (8%)

1.0

Current smoking, n (%)

14 (19%)

6 (17%)

8 (22%)

0.77

Alcohol drinking, n (%)

11 (15%)

8 (22%)

3 (8%)

0.19

WBC, × 10³/µL

9.8 (7.5 - 13.0)

9.7 (7.8 - 12.7)

10.0 (7.3 - 13.5)

0.91

Hb, g/dL

11.9 (10.9 - 12.8)

12.7 (11.8 - 13.5)

11.2 (10.6 - 12.1)

< 0.01

Alb, g/dL

3.3 (2.9 - 3.7)

3.4 (2.7 - 3.7)

0.68

CRP, mg/dL

1.17 (0.29 - 3.26)

1.46 (0.38 - 3.30)

0.89 (0.27 - 3.24)

0.50

ESR, mm/h

35 (19 - 48)

32 (17 - 43)

38 (22 - 49)

0.28

Medications at GMA initiation, n (%)

5-ASA

65 (90%)

32 (89%)

33 (92%)

1.0

AZA or 6-MP

8 (11%)

4 (11%)

1.0

PSL

57 (79%)

30 (83%)

27 (75%)

0.56

5-ASA dose, mg/day*

4,000 (3,600 - 4,800)

3,800 (3,600 - 4,000)

4,000 (3,600 - 4,800)

0.07

AZA or 6-MP dose, mg/kg/day*

0.95 (0.66, 1.18)

0.66 (0.60, 0.93)

0.98 (0.96 - 1.23)

0.15

Biologics within 1-year after GMA, n (%)

34 (47%)

15 (42%)

19 (53%)

0.48

GMA dose, mL/kg/session

34.2 (28.6 - 39.2)

28.6 (26.6 - 31.6)

39.3 (36.4 - 47.5)

< 0.01

GMA session treatment time (60 min/> 60 min), n

54/18

35/1

19/17

< 0.01

UC exacerbation within 1-year after GMA, n (%)

34 (47%)

23 (64%)

11 (31%)

< 0.01

**Table 2.** Disease Severity, Laboratory Data, and Medications After a Series of GMA Treatments
Variable	All (N = 72)	Lower GMA dose (N = 36)	Higher GMA dose (N = 36)	P
Continuous data are presented as median (IQR). Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte adsorption; Hb: hemoglobin; IQR: interquartile range; 6-MP: 6-mercaptopurine; PSL: prednisolone; WBC: white blood cell count.
Seo index (mild/moderate/severe), n	67/4/1	33/2/1	34/2/0	0.60
Seo index score	114 (105, 122)	114 (105, 121)	111 (105, 123)	0.89
clinical improvement/remission	60 (83%)	28 (78%)	32 (89%)	0.34
WBC, × 10³/µL	9.8 (7.1, 11.5)	10.5 (9.0, 11.7)	8.8 (6.6, 11.2)	0.09
Hb, g/dL	12.7 (11.0, 13.4)	12.7 (11.1, 13.7)	12.3 (10.5, 13.3)	0.27
Alb, g/dL	3.9 (3.7, 4.1)	3.8 (3.6, 4.2)	4.0 (3.7, 4.1)	0.33
CRP, mg/dL	0.05 (0.02, 0.15)	0.06 (0.03, 0.23)	0.02 (0.02, 0.10)	0.03
ESR, mm/h	13 (5, 23)	15 (6, 27)	12 (4, 19)	0.28
Medication after GMA, n (%)
5-ASA	67 (93%)	33 (92%)	34 (94%))	1.0
AZA or 6-MP	12 (17%)	6 (17%)	6 (17%)	1.0
PSL	61 (85%)	32 (89%)	29 (81%)	0.51

Table 2. Disease Severity, Laboratory Data, and Medications After a Series of GMA Treatments

Variable

All (N = 72)

Lower GMA dose (N = 36)

Higher GMA dose (N = 36)

Continuous data are presented as median (IQR). Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte adsorption; Hb: hemoglobin; IQR: interquartile range; 6-MP: 6-mercaptopurine; PSL: prednisolone; WBC: white blood cell count.

Seo index (mild/moderate/severe), n

67/4/1

33/2/1

34/2/0

0.60

Seo index score

114 (105, 122)

114 (105, 121)

111 (105, 123)

0.89

clinical improvement/remission

60 (83%)

28 (78%)

32 (89%)

0.34

WBC, × 10³/µL

9.8 (7.1, 11.5)

10.5 (9.0, 11.7)

8.8 (6.6, 11.2)

0.09

Hb, g/dL

12.7 (11.0, 13.4)

12.7 (11.1, 13.7)

12.3 (10.5, 13.3)

0.27

Alb, g/dL

3.9 (3.7, 4.1)

3.8 (3.6, 4.2)

4.0 (3.7, 4.1)

0.33

CRP, mg/dL

0.05 (0.02, 0.15)

0.06 (0.03, 0.23)

0.02 (0.02, 0.10)

0.03

ESR, mm/h

13 (5, 23)

15 (6, 27)

12 (4, 19)

0.28

Medication after GMA, n (%)

5-ASA

67 (93%)

33 (92%)

34 (94%))

1.0

AZA or 6-MP

12 (17%)

6 (17%)

1.0

PSL

61 (85%)

32 (89%)

29 (81%)

0.51

**Table 3.** Results of Univariate Cox Regression Analysis for 1-Year UC Exacerbation After GMA
Variable	HR (95% CI)	P
Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte adsorption; Hb: hemoglobin; 6-MP: 6-mercaptopurine; PSL: prednisolone; WBC: white blood cell count.
Age	0.98 (0.96 - 1.00)	0.08
Male gender	1.60 (0.75 - 3.44)	0.22
Body weight	1.03 (0.99 - 1.06)	0.07
UC duration	0.996 (0.96 - 1.03)	0.84
Total colitis (vs. hemi-sided colitis)	2.05 (0.89 - 4.71)	0.09
Clinical severity
Mild	1.88 (0.72 - 4.93)	0.20
Moderate	ref
Severe	1.08 (0.38 - 3.12)	0.88
Seo index
Mild	0.68 (0.30 - 1.55)	0.36
Moderate	ref
Severe	1.72 (0.72 - 4.10)	0.22
Seo index score	1.00 (0.99 - 1.01)	0.41
WBC	1.00 (1.00 - 1.00)	0.88
Hb	1.03 (0.84 - 1.27)	0.77
Alb	1.21 (0.70 - 2.08)	0.50
CRP	1.02 (0.94 - 1.10)	0.66
ESR	1.00 (0.98 - 1.01)	0.67
Medications at GMA initiation
5-ASA	1.04 (0.32 - 3.40)	0.95
AZA or 6-MP	0.17 (0.02 - 1.22)	0.08
PSL	2.52 (0.89 - 7.17)	0.08
Biologics within 1 year after GMA	1.13 (0.58 - 2.21)	0.72
High GMA dose (vs. low GMA dose)	0.39 (0.19 - 0.80)	0.01
> 60 min of GMA session (vs. 60 min)	0.47 (0.18 - 1.21)	0.12

Table 3. Results of Univariate Cox Regression Analysis for 1-Year UC Exacerbation After GMA

Variable

HR (95% CI)

Alb: serum albumin; 5-ASA: 5-aminosalicylic acid; AZA: azathioprine; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GMA: granulocyte and monocyte adsorption; Hb: hemoglobin; 6-MP: 6-mercaptopurine; PSL: prednisolone; WBC: white blood cell count.

Age

0.98 (0.96 - 1.00)

0.08

Male gender

1.60 (0.75 - 3.44)

0.22

Body weight

1.03 (0.99 - 1.06)

0.07

UC duration

0.996 (0.96 - 1.03)

0.84

Total colitis (vs. hemi-sided colitis)

2.05 (0.89 - 4.71)

0.09

Clinical severity

Mild

1.88 (0.72 - 4.93)

0.20

Moderate

ref

Severe

1.08 (0.38 - 3.12)

0.88

Seo index

Mild

0.68 (0.30 - 1.55)

0.36

Moderate

ref

Severe

1.72 (0.72 - 4.10)

0.22

Seo index score

1.00 (0.99 - 1.01)

0.41

WBC

1.00 (1.00 - 1.00)

0.88

1.03 (0.84 - 1.27)

0.77

Alb

1.21 (0.70 - 2.08)

0.50

CRP

1.02 (0.94 - 1.10)

0.66

ESR

1.00 (0.98 - 1.01)

0.67

Medications at GMA initiation

5-ASA

1.04 (0.32 - 3.40)

0.95

AZA or 6-MP

0.17 (0.02 - 1.22)

0.08

PSL

2.52 (0.89 - 7.17)

0.08

Biologics within 1 year after GMA

1.13 (0.58 - 2.21)

0.72

High GMA dose (vs. low GMA dose)

0.39 (0.19 - 0.80)

0.01

> 60 min of GMA session (vs. 60 min)

0.47 (0.18 - 1.21)

0.12

**Table 4.** Results From Multivariate Cox Proportional Hazards Model for UC Exacerbation Within 1 Year After GMA
Variable	HR (95% CI)	P
AZA: azathioprine; CI: confidence interval; GMA: granulocyte and monocyte apheresis; HR: hazard ratio; 6-MP: 6-mercaptopurine; PSL: prednisolone; UC: ulcerative colitis.
Model 1
Higher GMA dose (vs. lower GMA dose)	0.36 (0.17 - 0.78)	< 0.01
Age	0.98 (0.95 - 0.997)	0.03
Male gender	1.19 (0.53 - 2.68)	0.67
Model 2
Higher GMA dose (vs. lower GMA dose)	0.37 (0.17 - 0.81)	0.01
Age	0.97 (0.94 - 0.998)	0.04
Duration of UC	1.02 (0.97 - 1.07)	0.42
Total colitis (vs. hemi-sided colitis)	1.38 (0.56 - 3.38)	0.48
Model 3
Higher GMA dose (vs. lower GMA dose)	0.38 (0.18 - 0.78)	< 0.01
Age	0.98 (0.96 - 1.01)	0.16
AZA or 6-MP use	0.21 (0.03 - 1.61)	0.14
PSL use	1.61 (0.55 - 4.72)	0.39
Model 4
Higher GMA dose (vs. lower GMA dose)	0.30 (0.14 - 0.64)	< 0.01
Age	0.98 (0.96 - 1.00)	0.07
GMA prior to 2017 (vs. later)	0.58 (0.28 - 1.21)	0.15
Model 5
Higher GMA dose (vs. lower GMA dose)	0.35 (0.17 - 0.74)	< 0.01
Age	0.98 (0.96 - 0.999)	0.04
GMA before May 2019 (vs. later)	1.25 (0.58 - 2.67)	0.57

Table 4. Results From Multivariate Cox Proportional Hazards Model for UC Exacerbation Within 1 Year After GMA

Variable

HR (95% CI)

AZA: azathioprine; CI: confidence interval; GMA: granulocyte and monocyte apheresis; HR: hazard ratio; 6-MP: 6-mercaptopurine; PSL: prednisolone; UC: ulcerative colitis.

Model 1

Higher GMA dose (vs. lower GMA dose)

0.36 (0.17 - 0.78)

< 0.01

Age

0.98 (0.95 - 0.997)

0.03

Male gender

1.19 (0.53 - 2.68)

0.67

Model 2

Higher GMA dose (vs. lower GMA dose)

0.37 (0.17 - 0.81)

0.01

Age

0.97 (0.94 - 0.998)

0.04

Duration of UC

1.02 (0.97 - 1.07)

0.42

Total colitis (vs. hemi-sided colitis)

1.38 (0.56 - 3.38)

0.48

Model 3

Higher GMA dose (vs. lower GMA dose)

0.38 (0.18 - 0.78)

< 0.01

Age

0.98 (0.96 - 1.01)

0.16

AZA or 6-MP use

0.21 (0.03 - 1.61)

0.14

PSL use

1.61 (0.55 - 4.72)

0.39

Model 4

Higher GMA dose (vs. lower GMA dose)

0.30 (0.14 - 0.64)

< 0.01

Age

0.98 (0.96 - 1.00)

0.07

GMA prior to 2017 (vs. later)

0.58 (0.28 - 1.21)

0.15

Model 5

Higher GMA dose (vs. lower GMA dose)

0.35 (0.17 - 0.74)

< 0.01

Age

0.98 (0.96 - 0.999)

0.04

GMA before May 2019 (vs. later)

1.25 (0.58 - 2.67)

0.57

**Table 5.** Safety of GMA Sessions With Standard and Extended Treatment Time
	Sessions with standard treatment time (N = 540)	Sessions with extended treatment time (N = 180)	P
Less than 1,800 mL of actual processed blood volume in the session, n (%)	29 (5.4%)	5 (2.8%)	0.22
Unexpected termination of the session, n (%)	29 (5.4%)	16 (8.9%)	0.13
Cause of unexpected termination, n (%)
Circuit coagulation	19 (3.5%)	11 (5.6%)	0.32
Defecation	2 (0.4%)	5 (2.8%)	0.01
Allergy (because of anticoagulant)	3 (0.6%)	0 (0%)	0.58
Impossible draining of blood from the body	5 (0.9%)	0 (0%)	0.34

Table 5. Safety of GMA Sessions With Standard and Extended Treatment Time

Sessions with standard treatment time (N = 540)

Sessions with extended treatment time (N = 180)

Less than 1,800 mL of actual processed blood volume in the session, n (%)

29 (5.4%)

5 (2.8%)

0.22

Unexpected termination of the session, n (%)

29 (5.4%)

16 (8.9%)

0.13

Cause of unexpected termination, n (%)

Circuit coagulation

19 (3.5%)

11 (5.6%)

0.32

Defecation

2 (0.4%)

5 (2.8%)

0.01

Allergy (because of anticoagulant)

3 (0.6%)

0 (0%)

0.58

Impossible draining of blood from the body

5 (0.9%)

0 (0%)

0.34