Novel association between graft rejection and post-transplant malignancy in solid organ transplantation

doi:10.5500/wjt.v15.i2.102384

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World Journal of Transplantation

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2220-3230

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Transplant. Jun 18, 2025; 15(2): 102384
Published online Jun 18, 2025. doi: 10.5500/wjt.v15.i2.102384

Table 1 Peri-transplant clinical and immunological characteristics, n (%)/mean ± SD

Variable	Transplant organ type						P value
Variable	Total	Kidney	Liver	Heart	Lung	Pancreas	P value
Number of patients	579905	386878	108390	45046	37643	1948
Age (years)	50.6 ± 13.2	49.4 ± 13.8	52.8 ± 10.9	52.6 ± 12.4	55.0 ± 12.9	41.2 ± 9.9	< 0.001
Female	220273 (38.0)	153116 (39.6)	39064 (36.0)	10967 (24.3)	15971 (42.4)	1155 (59.3)	< 0.001
Race							< 0.001
White	337778 (58.3)	194112 (50.2)	80251 (74.0)	31015 (68.9)	30576 (81.2)	1824 (93.7)
Black	121654 (21.0)	101431 (26.2)	8244 (7.6)	8626 (19.2)	3292 (8.7)	61 (3.1)
Hispanic	82617 (14.2)	61585 (15.9)	14579 (13.5)	3612 (8.0)	2791 (7.4)	50 (2.6)
Asian	29030 (5.0)	22979 (5.9)	3979 (3.7)	1346 (3.0)	721 (1.9)	5 (0.3)
Other	8786 (1.5)	6755 (1.7)	1323 (1.2)	441 (1.0)	260 (0.7)	7 (0.4)
Body mass index							< 0.001
< 25 kg/m²	203355 (35.1)	135071 (34.9)	33191 (30.6)	15905 (35.3)	18249 (48.5)	939 (48.2)
25-30 kg/m²	193173 (33.3)	125232 (32.4)	37188 (34.3)	16617 (36.9)	13423 (35.7)	713 (36.6)
	174940 (30.2)	118752 (30.7)	37658 (34.7)	12374 (27.5)	5885 (15.6)	271 (13.9)
Performance status							< 0.001
ECOG ≥ 2	164472 (28.4)	47819 (12.4)	59733 (55.1)	29247 (64.9)	27429 (72.9)	244 (12.5)
ABO blood group							< 0.001
O	257752 (44.4)	175278 (45.3)	47570 (43.9)	17122 (38.0)	16954 (45.0)	828 (42.5)
A	217263 (37.5)	141574 (36.6)	41074 (37.9)	18848 (41.8)	14941 (39.7)	826 (42.4)
B	77272 (13.3)	51850 (13.4)	14320 (13.2)	6621 (14.7)	4262 (11.3)	219 (11.2)
AB	27608 (4.8)	18166 (4.7)	5426 (5.0)	2455 (5.4)	1486 (3.9)	75 (3.9)
ABO mismatch	4844 (0.8)	3810 (1.0)	1020 (0.9)	5 (0.0)	6 (0.0)	3 (0.2)	< 0.001
HLA mismatch¹	477075 (82.3)	355193 (91.8)	46501 (42.9)	39707 (88.1)	33761 (89.7)	1913 (98.2)	< 0.001
CMV seropositive	297861 (51.4)	198117 (51.2)	58330 (53.8)	21827 (48.5)	18847 (50.1)	740 (38.0)	< 0.001
EBV seropositive	354259 (61.1)	229647 (59.4)	65178 (60.1)	29899 (66.4)	28268 (75.1)	1267 (65.0)	< 0.001
HBV seropositive	11417 (2.0)	5819 (1.5)	4492 (4.1)	614 (1.4)	478 (1.3)	14 (0.7)	< 0.001
HCV seropositive	46978 (8.1)	14395 (3.7)	30915 (28.5)	901 (2.0)	732 (1.9)	35 (1.8)	< 0.001
HIV seropositive	3171 (0.5)	2522 (0.7)	474 (0.4)	118 (0.3)	54 (0.1)	3 (0.2)	< 0.001
Donor type							< 0.001
Deceased	442198 (76.3)	254296 (65.7)	103331 (95.3)	45027 (100.0)	37607 (99.9)	1937 (99.4)
Living	137671 (23.7)	132547 (34.3)	5059 (4.7)	19 (0.0)	36 (0.1)	10 (0.5)
Induction therapy	444018 (76.6)	311970 (80.6)	68458 (63.2)	32960 (73.2)	28975 (77.0)	1655 (85.0)	< 0.001
rATG	163501 (28.2)	147287 (38.1)	7401 (6.8)	6495 (14.4)	1228 (3.3)	1090 (56.0)	< 0.001
Basiliximab	107968 (18.6)	66528 (17.2)	15357 (14.2)	8835 (19.6)	17144 (45.5)	104 (5.3)	< 0.001
Alemtuzumab	39680 (6.8)	36968 (9.6)	425 (0.4)	380 (0.8)	1645 (4.4)	262 (13.4)	< 0.001
Tacrolimus	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Cyclosporine	26218 (4.5)	18297 (4.7)	1874 (1.7)	3805 (8.4)	2173 (5.8)	69 (3.5)	< 0.001
Mycophenolate mofetil	20502 (3.5)	17529 (4.5)	1638 (1.5)	945 (2.1)	337 (0.9)	53 (2.7)	< 0.001
Azathioprine	19417 (3.3)	12275 (3.2)	1530 (1.4)	3368 (7.5)	2167 (5.8)	77 (4.0)	< 0.001
Glucocorticoid	363820 (62.7)	249121 (64.4)	60017 (55.4)	29076 (64.5)	24400 (64.8)	1206 (61.9)	< 0.001
Sirolimus	4634 (0.8)	4243 (1.1)	314 (0.3)	45 (0.1)	4 (0.0)	28 (1.4)	< 0.001
Everolimus	157 (0.0)	127 (0.0)	12 (0.0)	17 (0.0)	1 (0.0)	0 (0.0)	< 0.001
Rituximab	3731 (0.6)	1853 (0.5)	1456 (1.3)	106 (0.2)	305 (0.8)	11 (0.6)	< 0.001
Maintenance therapy	564847 (97.4)	378428 (97.8)	104051 (96.0)	43318 (96.2)	37229 (98.9)	1821 (93.5)	< 0.001
rATG	321 (0.1)	290 (0.1)	17 (0.0)	9 (0.0)	3 (0.0)	2 (0.1)	< 0.001
Basiliximab	329 (0.1)	215 (0.1)	57 (0.1)	27 (0.1)	28 (0.1)	2 (0.1)	0.510
Alemtuzumab	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Tacrolimus	144998 (25.0)	93180 (24.1)	26497 (24.4)	13778 (30.6)	11312 (30.1)	231 (11.9)	< 0.001
Cyclosporine	121422 (20.9)	91543 (23.7)	13157 (12.1)	10375 (23.0)	6225 (16.5)	122 (6.3)	< 0.001
Mycophenolate mofetil	451378 (77.8)	309403 (80.0)	77099 (71.1)	37025 (82.2)	26278 (69.8)	1573 (80.7)	< 0.001
Azathioprine	62294 (10.7)	41029 (10.6)	6788 (6.3)	4820 (10.7)	9555 (25.4)	102 (5.2)	< 0.001
Glucocorticoid	457017 (78.8)	292533 (75.6)	86605 (79.9)	40619 (90.2)	36116 (95.9)	1144 (58.7)	< 0.001
Sirolimus	17850 (3.1)	14636 (3.8)	2371 (2.2)	461 (1.0)	148 (0.4)	234 (12.0)	< 0.001
Everolimus	2307 (0.4)	1606 (0.4)	483 (0.4)	204 (0.5)	7 (0.0)	7 (0.4)	< 0.001
Rituximab	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Antirejection therapy	33922 (5.8)	16972 (4.4)	8325 (7.7)	5049 (11.2)	3530 (9.4)	46 (2.4)	< 0.001
rATG	5334 (0.9)	4102 (1.1)	438 (0.4)	596 (1.3)	180 (0.5)	18 (0.9)	< 0.001
Basiliximab	1626 (0.3)	1335 (0.3)	181 (0.2)	50 (0.1)	57 (0.2)	3 (0.2)	< 0.001
Alemtuzumab	99 (0.0)	75 (0.0)	14 (0.0)	1 (0.0)	9 (0.0)	0 (0.0)	0.050
Tacrolimus	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Cyclosporine	2974 (0.5)	1677 (0.4)	1087 (1.0)	159 (0.4)	50 (0.1)	1 (0.1)	< 0.001
Mycophenolate mofetil	1040 (0.2)	620 (0.2)	280 (0.3)	96 (0.2)	43 (0.1)	1 (0.1)	< 0.001
Azathioprine	1792 (0.3)	1094 (0.3)	564 (0.5)	85 (0.2)	49 (0.1)	0 (0.0)	< 0.001
Glucocorticoid	30156 (5.2)	14174 (3.7)	7937 (7.3)	4690 (10.4)	3319 (8.8)	36 (1.8)	< 0.001
Sirolimus	128 (0.0)	100 (0.0)	16 (0.0)	7 (0.0)	5 (0.0)	0 (0.0)	0.101
Everolimus	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Rituximab	456 (0.1)	164 (0.0)	24 (0.0)	148 (0.3)	119 (0.3)	1 (0.1)	< 0.001

¹HLA mismatch referred to a mismatch at one or more loci (HLA-A, -B, -DR) between the recipients and their donors.

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; ECOG: Eastern Cooperative Oncology Group; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HLA: Human leukocyte antigen; NA: Not available; rATG: Rabbit anti-thymocyte globulin; SD: Standard deviation.

Table 2 Post-transplant clinical outcomes, n (%)

Variable	Transplant organ type						P value
Variable	Total	Kidney	Liver	Heart	Lung	Pancreas	P value
Number of patients	579905	386878	108390	45046	37643	1948
Rejection-induced graft failure	55240 (9.5)	46815 (12.1)	1951 (1.8)	1770 (3.9)	4505 (12.0)	199 (10.2)	< 0.001
Acute rejection graft failure	12282 (2.1)	10424 (2.7)	746 (0.7)	646 (1.4)	302 (0.8)	164 (8.4)	< 0.001
Chronic rejection graft failure	43175 (7.4)	36391 (9.4)	1422 (1.3)	1124 (2.5)	4203 (11.2)	35 (1.8)	< 0.001
Retransplantation	36636 (6.3)	30367 (7.8)	4069 (3.8)	781 (1.7)	1214 (3.2)	205 (10.5)	< 0.001
Post-transplant malignancy	69838 (12.0)	38302 (9.9)	13414 (12.4)	9397 (20.9)	8505 (22.6)	220 (11.3)	< 0.001
Breast cancer	2706 (0.5)	1867 (0.5)	453 (0.4)	198 (0.4)	176 (0.5)	12 (0.6)	0.054
Digestive cancer	6696 (1.2)	3450 (0.9)	1771 (1.6)	722 (1.6)	745 (2.0)	8 (0.4)	< 0.001
Genitourinary cancer	9595 (1.7)	6114 (1.6)	1339 (1.2)	1490 (3.3)	639 (1.7)	13 (0.7)	< 0.001
Gynecologic cancer	708 (0.1)	492 (0.1)	121 (0.1)	35 (0.1)	55 (0.1)	5 (0.3)	0.008
Head and neck cancer	1853 (0.3)	941 (0.2)	546 (0.5)	204 (0.5)	159 (0.4)	3 (0.2)	< 0.001
Hematologic cancer	8094 (1.4)	4325 (1.1)	1808 (1.7)	918 (2.0)	995 (2.6)	48 (2.5)	< 0.001
Musculoskeletal cancer	329 (0.1)	177 (0.0)	59 (0.1)	41 (0.1)	50 (0.1)	2 (0.1)	< 0.001
Neurologic cancer	42 (0.0)	29 (0.0)	4 (0.0)	3 (0.0)	6 (0.0)	0 (0.0)	0.198
Respiratory cancer	6523 (1.1)	2980 (0.8)	1532 (1.4)	1089 (2.4)	911 (2.4)	11 (0.6)	< 0.001
Skin cancer/Kaposi sarcoma	37061 (6.4)	19411 (5.0)	6230 (5.7)	5763 (12.8)	5529 (14.7)	128 (6.6)	< 0.001
Unknown primary cancer	572 (0.1)	330 (0.1)	101 (0.1)	74 (0.2)	66 (0.2)	1 (0.1)	< 0.001
Other cancer	6093 (1.1)	3322 (0.9)	1276 (1.2)	733 (1.6)	734 (1.9)	28 (1.4)	< 0.001
Death	228813 (39.5)	148606 (38.4)	39082 (36.1)	18542 (41.2)	22030 (58.5)	553 (28.4)	< 0.001

Table 3 Landmark analysis of post-transplant malignancy risk in rejection-induced graft failure, n (%)

Variable	Post-transplant malignancy	Post-transplant malignancy risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Rejection-induced graft failure
No landmark (n = 55240)	3973 (7.19)	0.44 (0.43-0.46)	< 0.001	0.70 (0.68-0.73)	< 0.001
1-year landmark (n = 7622)	58 (0.76)	0.11 (0.09-0.14)	< 0.001	0.20 (0.16-0.26)	< 0.001
2-year landmark (n = 9830)	63 (0.64)	0.09 (0.07-0.11)	< 0.001	0.16 (0.13-0.21)	< 0.001
3-year landmark (n = 11942)	69 (0.58)	0.08 (0.06-0.10)	< 0.001	0.14 (0.11-0.18)	< 0.001
5-year landmark (n = 14094)	62 (0.44)	0.06 (0.05-0.07)	< 0.001	0.11 (0.08-0.14)	< 0.001
10-year landmark (n = 11716)	44 (0.38)	0.05 (0.04-0.07)	< 0.001	0.09 (0.07-0.12)	< 0.001
15-year landmark (n = 5545)	25 (0.45)	0.07 (0.05-0.11)	< 0.001	0.11 (0.07-0.16)	< 0.001
20-year landmark (n = 1882)	5 (0.27)	0.05 (0.02-0.11)	< 0.001	0.07 (0.03-0.16)	< 0.001
Excluding rejection-related retransplantation
No landmark (n = 39334)	3222 (8.19)	0.53 (0.51-0.55)	< 0.001	0.74 (0.72-0.77)	< 0.001
1-year landmark (n = 5690)	51 (0.90)	0.14 (0.11-0.18)	< 0.001	0.22 (0.17-0.30)	< 0.001
2-year landmark (n = 7022)	54 (0.77)	0.11 (0.08-0.14)	< 0.001	0.18 (0.14-0.24)	< 0.001
3-year landmark (n = 8240)	56 (0.68)	0.09 (0.07-0.12)	< 0.001	0.15 (0.12-0.20)	< 0.001
5-year landmark (n = 9373)	54 (0.58)	0.07 (0.06-0.10)	< 0.001	0.12 (0.10-0.16)	< 0.001
10-year landmark (n = 7655)	33 (0.43)	0.06 (0.04-0.08)	< 0.001	0.09 (0.07-0.13)	< 0.001
15-year landmark (n = 3694)	16 (0.43)	0.07 (0.04-0.11)	< 0.001	0.09 (0.05-0.15)	< 0.001
20-year landmark (n = 1283)	5 (0.39)	0.06 (0.03-0.15)	< 0.001	0.20 (0.11-0.36)	< 0.001
Excluding rejection-related mortality
No landmark (n = 25856)	1332 (5.15)	0.32 (0.30-0.33)	< 0.001	0.69 (0.65-0.73)	< 0.001
1-year landmark (n = 3077)	14 (0.45)	0.08 (0.05-0.14)	< 0.001	0.21 (0.13-0.36)	< 0.001
2-year landmark (n = 4099)	17 (0.41)	0.07 (0.04-0.11)	< 0.001	0.18 (0.11-0.28)	< 0.001
3-year landmark (n = 5075)	21 (0.41)	0.07 (0.04-0.10)	< 0.001	0.17 (0.11-0.26)	< 0.001
5-year landmark (n = 5910)	13 (0.22)	0.04 (0.02-0.06)	< 0.001	0.09 (0.05-0.15)	< 0.001
10-year landmark (n = 4662)	17 (0.36)	0.07 (0.04-0.10)	< 0.001	0.13 (0.08-0.21)	< 0.001
15-year landmark (n = 2068)	12 (0.58)	0.12 (0.07-0.20)	< 0.001	0.20 (0.12-0.36)	< 0.001
20-year landmark (n = 662)	2 (0.30)	0.07 (0.02-0.26)	< 0.001	0.24 (0.09-0.60)	0.003

CI: Confidence interval; HR: Hazard ratio.

Table 4 Time-dependent Cox proportional hazards regression analysis of post-transplant malignancy risk in rejection-induced graft failure

Covariate (Time-dependent)	Transplant organ	Post-transplant malignancy risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Rejection-induced graft failure	Total	0.12 (0.11-0.13)	< 0.001	0.21 (0.19-0.24)	< 0.001
	Kidney	0.14 (0.12-0.16)	< 0.001	0.21 (0.18-0.23)	< 0.001
	Liver	0.50 (0.13-2.01)	0.33	0.001 (0.00-7.31E+17)	0.79
	Heart	0.29 (0.07-1.17)	0.08	0.52 (0.13-2.06)	0.35
	Lung	0.44 (0.24-0.82)	0.01	0.44 (0.22-0.89)	0.02
	Pancreas	0.19 (0.03-1.33)	0.09	0.20 (0.03-1.44)	0.11
Excluding rejection-related retransplantation	Total	0.14 (0.12-0.16)	< 0.001	0.23 (0.20-0.26)	< 0.001
	Kidney	0.17 (0.15-0.19)	< 0.001	0.22 (0.20-0.26)	< 0.001
	Liver	0.78 (0.20-3.13)	0.73	0.96 (0.24-3.85)	0.96
	Heart	0.18 (0.03-1.30)	0.09	0.29 (0.04-2.03)	0.21
	Lung	0.44 (0.22-0.88)	0.02	0.46 (0.23-0.91)	0.03
	Pancreas	0.28 (0.04-2.03)	0.21	0.31 (0.04-2.25)	0.25
Excluding rejection-related mortality	Total	0.11 (0.09-0.13)	< 0.001	0.25 (0.21-0.31)	< 0.001
	Kidney	0.13 (0.11-0.16)	< 0.001	0.25 (0.20-0.31)	< 0.001
	Liver	0.05 (0.00-68.29)	0.42	0.004 (0.00-2.86E+11)	0.74
	Heart	0.49 (0.07-3.46)	0.47	0.82 (0.12-5.83)	0.84
	Lung	0.55 (0.18-1.72)	0.31	0.77 (0.25-2.37)	0.64
	Pancreas	0.05 (0.00-8.78)	0.25	0.00 (0.00-9.80E+190)	0.96

CI: Confidence interval; HR: Hazard ratio.

Table 5 Landmark analysis of rejection-induced graft failure risk in post-transplant malignancy, n (%)

Variable	Rejection-induced graft failure	Rejection-induced graft failure risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Post-transplant malignancy
No landmark (n = 69838)	3973 (5.69)	0.35 (0.34-0.36)	< 0.001	0.42 (0.40-0.43)	< 0.001
1-year landmark (n = 13945)	710 (5.09)	0.60 (0.56-0.65)	< 0.001	0.85 (0.79-0.92)	< 0.001
2-year landmark (n = 18856)	983 (5.21)	0.60 (0.57-0.64)	< 0.001	0.85 (0.80-0.91)	< 0.001
3-year landmark (n = 22758)	1155 (5.08)	0.59 (0.55-0.62)	< 0.001	0.84 (0.79-0.89)	< 0.001
5-year landmark (n = 26630)	1336 (5.02)	0.59 (0.56-0.63)	< 0.001	0.84 (0.79-0.89)	< 0.001
10-year landmark (n = 24023)	1152 (4.80)	0.69 (0.65-0.73)	< 0.001	0.89 (0.84-0.95)	< 0.001
15-year landmark (n = 14884)	667 (4.48)	0.88 (0.81-0.96)	0.003	1.06 (0.97-1.16)	0.22
20-year landmark (n = 7581)	283 (3.73)	0.99 (0.87-1.14)	0.93	1.12 (0.96-1.31)	0.14
Excluding malignancy-related mortality
No landmark (n = 29830)	1332 (4.47)	0.25 (0.24-0.26)	< 0.001	0.31 (0.29-0.33)	< 0.001
1-year landmark (n = 6596)	214 (3.24)	0.34 (0.30-0.39)	< 0.001	0.51 (0.44-0.58)	< 0.001
2-year landmark (n = 9060)	277 (3.06)	0.32 (0.28-0.36)	< 0.001	0.49 (0.44-0.56)	< 0.001
3-year landmark (n = 10943)	327 (2.99)	0.31 (0.28-0.35)	< 0.001	0.49 (0.44-0.55)	< 0.001
5-year landmark (n = 12790)	422 (3.30)	0.36 (0.32-0.39)	< 0.001	0.56 (0.50-0.61)	< 0.001
10-year landmark (n = 11564)	423 (3.66)	0.48 (0.44-0.53)	< 0.001	0.67 (0.60-0.74)	< 0.001
15-year landmark (n = 7287)	270 (3.71)	0.66 (0.59-0.75)	< 0.001	0.80 (0.70-0.91)	< 0.001
20-year landmark (n = 3587)	124 (3.46)	0.77 (0.64-0.93)	0.01	0.84 (0.68-1.03)	0.10

CI: Confidence interval; HR: Hazard ratio.

Table 6 Time-dependent Cox proportional hazards regression analysis of rejection-induced graft failure risk in post-transplant malignancy

Covariate (Time-dependent)	Transplant organ	Rejection-induced graft failure risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Post-transplant malignancy	Total	0.81 (0.78-0.84)	< 0.001	1.11 (1.07-1.15)	< 0.001
	Kidney	0.81 (0.78-0.85)	< 0.001	1.14 (1.10-1.19)	< 0.001
	Liver	0.64 (0.50-0.81)	< 0.001	0.93 (0.67-1.29)	0.67
	Heart	0.58 (0.50-0.69)	< 0.001	0.83 (0.69-0.99)	0.04
	Lung	1.04 (0.96-1.13)	0.30	1.11 (1.02-1.21)	0.02
	Pancreas	1.07 (0.49-2.33)	0.87	1.16 (0.50-2.69)	0.74
Excluding malignancy-related mortality	Total	0.50 (0.47-0.52)	< 0.001	0.69 (0.65-0.73)	< 0.001
	Kidney	0.65 (0.62-0.69)	< 0.001	0.90 (0.84-0.95)	< 0.001
	Liver	0.15 (0.08-0.27)	< 0.001	0.21 (0.11-0.38)	< 0.001
	Heart	0.15 (0.10-0.22)	< 0.001	0.21 (0.14-0.31)	< 0.001
	Lung	0.17 (0.13-0.22)	< 0.001	0.18 (0.14-0.23)	< 0.001
	Pancreas	1.30 (0.57-3.01)	0.54	1.62 (0.69-3.77)	0.27

CI: Confidence interval; HR: Hazard ratio.

Table 7 Time-dependent Cox proportional hazards regression analysis of post-transplant malignancy risk in rejection-induced graft failure stratified by clinical characteristics

Covariate (Time-dependent)	Clinical characteristics	Post-transplant malignancy risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Rejection-induced graft failure	Age ≤ 51	0.13 (0.11-0.15)	< 0.001	0.20 (0.17-0.23)	< 0.001
	Age > 51	0.16 (0.13-0.19)	< 0.001	0.22 (0.19-0.26)	< 0.001
	BMI < 25	0.12 (0.10-0.14)	< 0.001	0.22 (0.18-0.26)	< 0.001
	BMI ≥ 25	0.11 (0.10-0.13)	< 0.001	0.21 (0.18-0.24)	< 0.001
	HLA match	0.18 (0.12-0.28)	< 0.001	0.23 (0.15-0.37)	< 0.001
	HLA mismatch²	0.12 (0.10-0.13)	< 0.001	0.21 (0.19-0.24)	< 0.001
	Living donor	0.13 (0.11-0.17)	< 0.001	0.21 (0.17-0.26)	< 0.001
	Deceased donor	0.11 (0.10-0.13)	< 0.001	0.22 (0.19-0.25)	< 0.001
	Induction therapy	0.12 (0.10-0.13)	< 0.001	0.21 (0.19-0.24)	< 0.001
	No induction therapy	0.12 (0.10-0.15)	< 0.001	0.21 (0.17-0.26)	< 0.001
	Year of transplant ≤ 2005	0.12 (0.10-0.14)	< 0.001	0.24 (0.16-0.36)	< 0.001
	Year of transplant > 2005	0.14 (0.11-0.17)	< 0.001	0.26 (0.21-0.32)	< 0.001

¹Multivariate analysis adjusted for age, sex, race/ethnicity, body mass index, performance status, ABO blood group, ABO match status, human leukocyte antigen match status, oncogenic virus seropositivity, donor type, and immunosuppressive therapy. Subgroup analyses excluded adjustment for the specific subgroup variable (e.g., age subgroups were not adjusted for age but adjusted for all other variables).

²Human leukocyte antigen mismatch referred to a mismatch at one or more loci (human leukocyte antigen -A, -B, -DR) between the recipients and their donors.

CI: Confidence interval; HR: Hazard ratio; HLA: Human leukocyte antigen.

Table 8 Time-dependent Cox proportional hazards regression analysis of rejection-induced graft failure risk in post-transplant malignancy stratified by clinical characteristics

Covariate (Time-dependent)	Clinical characteristics	Rejection-induced graft failure risk
		Univariate		Multivariate¹
		HR (95%CI)	P value	HR (95%CI)	P value
Post-transplant malignancy	Age ≤ 51	0.93 (0.89-0.97)	0.002	1.17 (1.11-1.23)	< 0.001
	Age > 51	0.98 (0.93-1.03)	0.37	1.06 (1.00-1.11)	0.04
	BMI < 25	0.84 (0.80-0.88)	< 0.001	1.11 (1.05-1.17)	< 0.001
	BMI ≥ 25	0.80 (0.76-0.84)	< 0.001	1.12 (1.07-1.18)	< 0.001
	HLA match	0.77 (0.66-0.90)	0.001	0.95 (0.81-1.12)	0.52
	HLA mismatch²	0.81 (0.79-0.84)	< 0.001	1.13 (1.09-1.18)	< 0.001
	Living donor	0.77 (0.72-0.83)	< 0.001	1.12 (1.08-1.17)	< 0.001
	Deceased donor	0.82 (0.79-0.86)	< 0.001	1.13 (1.05-1.21)	< 0.001
	Induction therapy	0.80 (0.77-0.83)	< 0.001	1.10 (1.06-1.15)	< 0.001
	No induction therapy	0.84 (0.79-0.90)	< 0.001	1.16 (1.08-1.23)	< 0.001
	Year of transplant ≤ 2005	0.86 (0.83-0.90)	< 0.001	1.12 (0.97-1.28)	0.12
	Year of transplant > 2005	0.85 (0.81-0.90)	< 0.001	1.04 (0.97-1.10)	0.27

²Human leukocyte antigen mismatch referred to a mismatch at one or more loci (human leukocyte antigen-A, -B, -DR) between the recipients and their donors.

CI: Confidence interval; HR: Hazard ratio; HLA: Human leukocyte antigen.

Citation: Kim HS, Woo W, Choi YG, Bharat A, Chae YK. Novel association between graft rejection and post-transplant malignancy in solid organ transplantation. World J Transplant 2025; 15(2): 102384
URL: https://www.wjgnet.com/2220-3230/full/v15/i2/102384.htm
DOI: https://dx.doi.org/10.5500/wjt.v15.i2.102384