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://www.thejh.org

Original Article

Volume 11, Number 2, April 2022, pages 45-54

Site-Specific Survival of Extra Nodal Diffuse Large B-Cell Lymphoma and Comparison With Gastrointestinal Diffuse Large B-Cell Lymphoma

Figure 1. Flowchart showing the patient selection and exclusion for the study. Patients diagnosed between 2000 and 2015 and listed in SEER 18 registries database were included in the study. Date cutoff for last follow-up was December 31, 2018. DLBCL: diffuse large B-cell lymphoma.

Figure 2. Kaplan-Meier curve showing effect of (a) age of onset categorized as age < 60 years and age ≥ 60 years, (b) gender, (c) ethnicity categorized as non-Hispanic white, non-Hispanic black, Hispanic, Asian, and others, (d) stage categorized as early stage which includes stage 1 and stage 2 diseases, and late stage which includes stage 3 and stage 4 diseases, and (e) past history of cancer.

Figure 3. Kaplan-Meier curve showing overall survival probability based on the site of the EN-DLBCL. (a) Overall survival probability for the site with better survival than the gastrointestinal tract. (b) Overall survival probability for the site with worse survival than the gastrointestinal tract. EN-DLBCL: extra nodal diffuse large B-cell lymphoma.

**Table 1.** Demographic and Clinical characteristic of the Study Population
Characteristics	Patients (n)	Percentage
Gender
Male	16,641	54.94
Female	13,649	45.06
Ethnicity
Non-Hispanic white	21,664	71.52
Asian American	1,969	6.50
Hispanic	3,824	12.62
Asian	2,606	8.60
Other	227	0.75
Site
Gastrointestinal tract	8,574	28.31
Bone marrow	749	2.47
Breast	754	2.49
Endocrine organs	1,108	3.66
Genitourinary	2,194	7.24
Head and neck	3,572	11.79
Heart and mediastinum	992	3.28
Musculoskeletal	1,757	5.80
Nervous system	4,174	13.78
Others	698	2.30
Pancreas and hepatobiliary	1,261	4.16
Respiratory tract	1,566	5.17
Skin and soft tissue	2,891	9.54
Stage
Early	21,001	69.33
Stage 1	14,827	48.95
Stage 2	6,174	20.38
Late	9,289	30.67
Stage 3	1,544	5.10
Stage 4	7,745	25.57
History of cancer
No	24,804	81.89
Yes	5,486	18.11
Age of onset
Early (< 60 years)	10,266	33.89
Late (≥ 60 years)	20,024	66.11

Table 1. Demographic and Clinical characteristic of the Study Population

Characteristics

Patients (n)

Percentage

Gender

Male

16,641

54.94

Female

13,649

45.06

Ethnicity

Non-Hispanic white

21,664

71.52

Asian American

1,969

6.50

Hispanic

3,824

12.62

Asian

2,606

8.60

Other

227

0.75

Site

Gastrointestinal tract

8,574

28.31

Bone marrow

749

2.47

Breast

754

2.49

Endocrine organs

1,108

3.66

Genitourinary

2,194

7.24

Head and neck

3,572

11.79

Heart and mediastinum

992

3.28

Musculoskeletal

1,757

5.80

Nervous system

4,174

13.78

Others

698

2.30

Pancreas and hepatobiliary

1,261

4.16

Respiratory tract

1,566

5.17

Skin and soft tissue

2,891

9.54

Stage

Early

21,001

69.33

Stage 1

14,827

48.95

Stage 2

6,174

20.38

Late

9,289

30.67

Stage 3

1,544

5.10

Stage 4

7,745

25.57

History of cancer

24,804

81.89

Yes

5,486

18.11

Age of onset

Early (< 60 years)

10,266

33.89

Late (≥ 60 years)

20,024

66.11

**Table 2.** Univariate and Multivariate analysis for Overall Survival with Cox-Proportional Hazard Model
Characteristics	Univariate HR	P-value	Multivariate HR	P-value
HR: hazard ratio.
Gender
Female	Reference		Reference
Male	1.04 (1.01-1.07)	0.01	1.08 (1.05 - 1.12)	< 0.001
Race
Non-Hispanic white	Reference		Reference
Non-Hispanic black	0.96 (0.90 - 1.02)	0.16	1.27 (1.19 - 1.34)	< 0.001
Hispanic	0.90 (0.86 - 0.94)	< 0.001	1.04 (0.99 - 1.09)	0.11
Asians	0.94 (0.89 - 0.99)	0.01	0.98 (0.93 - 1.03)	0.48
Others	0.62 (0.50 - 0.76)	< 0.001	0.79 (0.64 - 0.97)	0.03
Age
Early (< 60 years)	Reference		Reference
Late (≥ 60 years)	2.73 (2.64 - 2.83)	< 0.001	2.69 (2.59 - 2.79)	< 0.001
Stage
Early	Reference		Reference
Late	1.43 (1.41 - 1.46)	< 0.001	1.42 (1.37 - 1.47)	< 0.001
History of cancer
No	Reference		Reference
Yes	1.54 (1.49 - 1.60)	< 0.001	1.29 (1.24 - 1.33)	< 0.001

Table 2. Univariate and Multivariate analysis for Overall Survival with Cox-Proportional Hazard Model

Characteristics

Univariate HR

P-value

Multivariate HR

P-value

HR: hazard ratio.

Gender

Female

Reference

Male

1.04 (1.01-1.07)

0.01

1.08 (1.05 - 1.12)

< 0.001

Race

Non-Hispanic white

Reference

Non-Hispanic black

0.96 (0.90 - 1.02)

0.16

1.27 (1.19 - 1.34)

< 0.001

Hispanic

0.90 (0.86 - 0.94)

< 0.001

1.04 (0.99 - 1.09)

0.11

Asians

0.94 (0.89 - 0.99)

0.01

0.98 (0.93 - 1.03)

0.48

Others

0.62 (0.50 - 0.76)

< 0.001

0.79 (0.64 - 0.97)

0.03

Age

Early (< 60 years)

Reference

Late (≥ 60 years)

2.73 (2.64 - 2.83)

< 0.001

2.69 (2.59 - 2.79)

< 0.001

Stage

Early

Reference

Late

1.43 (1.41 - 1.46)

< 0.001

1.42 (1.37 - 1.47)

< 0.001

History of cancer

Reference

Yes

1.54 (1.49 - 1.60)

< 0.001

1.29 (1.24 - 1.33)

< 0.001

**Table 3.** Site-Specific Univariate and Multivariate analysis for Overall Survival With Cox-Proportional Hazard Model
	Median survival in months (95% CI)	Univariate HR (95% CI)	P-value	Multivariate HR (95% CI)	P-value
HR: hazard ratio; CI: confidence interval.
Gastrointestinal tract	58 (53 - 63)	Reference		Reference
Heart and mediastinum	NA	0.59 (0.50 - 0.69)	< 0.001	0.58 (0.51 - 0.66)	< 0.001
Musculoskeletal	174 (148 - 197)	0.61 (0.55 - 0.68)	< 0.001	0.59 (0.54 - 0.63)	< 0.001
Endocrine organs	120 (104 - 133)	0.74 (0.67 - 0.82)	< 0.001	0.73 (0.67 - 0.80)	< 0.001
Head and neck	92 (86 - 99)	0.78 (0.74 - 0.83)	< 0.001	0.77 (0.73 - 0.81)	< 0.001
Breast	93 (82 - 112)	0.75 (0.67 - 0.85)	< 0.001	0.79 (0.71 - 0.87)	< 0.001
Skin and soft tissue	77 (68 - 83)	0.85 (0.80 - 0.92)	< 0.001	0.83 (0.78 - 0.88)	< 0.001
Genitourinary	76 (70 - 87)	0.83 (0.77 - 0.90)	< 0.001	0.84 (0.79 - 0.89)	< 0.001
Bone marrow	22 (17 - 31)	0.87 (0.56 - 1.37)	0.55	1.03 (0.93 - 1.13)	0.54
Others	25 (15 - 41)	1.11 (0.84 - 1.29)	0.20	1.05 (0.96 - 1.16)	0.27
Respiratory tract	28 (22 - 39)	1.26 (1.14 - 1.38)	< 0.001	1.18 (1.10 - 1.26)	< 0.001
Pancreas and hepatobiliary	24 (17 - 38)	1.29 (1.17 - 1.42)	< 0.001	1.22 (1.13 - 1.31)	< 0.001
Nervous system	13 (11 - 14)	2.15 (2.04 - 2.26)	< 0.001	1.85 (1.77 - 1.93)	< 0.001

Table 3. Site-Specific Univariate and Multivariate analysis for Overall Survival With Cox-Proportional Hazard Model

Median survival in months (95% CI)

Univariate HR (95% CI)

P-value

Multivariate HR (95% CI)

P-value

HR: hazard ratio; CI: confidence interval.

Gastrointestinal tract

58 (53 - 63)

Reference

Heart and mediastinum

0.59 (0.50 - 0.69)

< 0.001

0.58 (0.51 - 0.66)

< 0.001

Musculoskeletal

174 (148 - 197)

0.61 (0.55 - 0.68)

< 0.001

0.59 (0.54 - 0.63)

< 0.001

Endocrine organs

120 (104 - 133)

0.74 (0.67 - 0.82)

< 0.001

0.73 (0.67 - 0.80)

< 0.001

Head and neck

92 (86 - 99)

0.78 (0.74 - 0.83)

< 0.001

0.77 (0.73 - 0.81)

< 0.001

Breast

93 (82 - 112)

0.75 (0.67 - 0.85)

< 0.001

0.79 (0.71 - 0.87)

< 0.001

Skin and soft tissue

77 (68 - 83)

0.85 (0.80 - 0.92)

< 0.001

0.83 (0.78 - 0.88)

< 0.001

Genitourinary

76 (70 - 87)

0.83 (0.77 - 0.90)

< 0.001

0.84 (0.79 - 0.89)

< 0.001

Bone marrow

22 (17 - 31)

0.87 (0.56 - 1.37)

0.55

1.03 (0.93 - 1.13)

0.54

Others

25 (15 - 41)

1.11 (0.84 - 1.29)

0.20

1.05 (0.96 - 1.16)

0.27

Respiratory tract

28 (22 - 39)

1.26 (1.14 - 1.38)

< 0.001

1.18 (1.10 - 1.26)

< 0.001

Pancreas and hepatobiliary

24 (17 - 38)

1.29 (1.17 - 1.42)

< 0.001

1.22 (1.13 - 1.31)

< 0.001

Nervous system

13 (11 - 14)

2.15 (2.04 - 2.26)

< 0.001

1.85 (1.77 - 1.93)

< 0.001