Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm

Table 1 Representative epidemiologic studies of malignancy risk after pediatric transplantation (solid organ transplantation and hematopoietic stem cell transplantation)

Ref.	Cohort	Country/registry	Transplant type	Age group	Sample size	Follow-up	Main reported risk estimates	Key notes (heterogeneity/era)
Yanik et al[7]	Transplant cancer match	United States; SRTR linked to 16 cancer registries	Pediatric SOT (kidney, liver, heart/Lung, intestine, multiorgan)	< 18 at transplant	17958 transplants	Median 4 years (max 22)	All cancers SIR 19.1; NHL/PTLD SIR 212; organ-specific NHL/PTLD SIRs: Kidney 159, liver 197, heart/Lung 318, intestine 1280; highest in first year post-transplant; EBV-higher risk	Demonstrates strong organ heterogeneity and early post-transplant peak; EBV mismatch/seronegativity is a major driver
Kitchlu et al[8]	Hospital for sick children, Ontario population cohort	Canada (Ontario)	Pediatric SOT (kidney/Liver/heart/Lung/multiorgan)	Pediatric	951 recipients	Mean 10.8 ± 7.1 years	Cumulative cancer incidence 20% vs 1.2% general population; incidence rate ratio 32.9; highest risk in first year (aHR 176); remains elevated > 10 years (aHR 10.8); lymphoproliferative disorders 77%	Highlights longer follow-up than many registry linkages and persistent excess risk beyond 10 years
Nordin et al[9]	Nordic liver transplant cohort	Nordic countries	Liver transplant (patients < 30 at liver transplantation; includes pediatric/young adult)	< 30 at transplant	923	7846 person-years; cumulative incidence reported to 25 years	All cancers SIR 9.8; cumulative incidence 2% (10 years), 6% (20 years), 22% (25 years)	Illustrates lower overall SIR vs United States pediatric SOT cohorts but rising absolute risk with long-term follow-up into young adulthood
Endén et al[10]	Finland nationwide pediatric SOT survivors	Finland	Kidney/Liver/heart SOT	< 16 at transplant	233	Median follow-up 18 years	Cancer HR 14.7 vs controls; PTLD approximately 78% of cancers; many cancers after age 18	Emphasizes late-occurring malignancy burden into adulthood and the need for lifelong surveillance
Ploos van Amstel et al[11]	Dutch pediatric ESRD transplant survivors	Netherlands	Mainly pediatric kidney transplant survivors (pediatric ESRD)	< 15 at transplant	249	Median 25.3 years; up to approximately 38 years	Overall malignancy risk IRR 21.7 vs general population; 41% cumulative incidence at 30 years (among survivors)	Demonstrates very long-term accumulation of malignancy risk decades after childhood transplant
Kahn et al[12]	CIBMTR; pediatric allogeneic HSCT for non-malignant diseases	International (CIBMTR)	HSCT (allogeneic; nonmalignant indications)	< 21	6028	Median follow-up 7.8 years	Subsequent neoplasms 1.2% (71 cases); SIR 11 (vs general population)	PTLD excluded as “subsequent neoplasm” in this analysis; shows elevated cancer risk even in nonmalignant HSCT settings
Bomken and Skinner[13]	Pediatric HSCT late effects	Review	HSCT (pediatric)	Pediatric			SMNs up to approximately 7% by 20 years post-HSCT; PTLD often early (≤ 2 years)	Useful for framing latency differences (PTLD early vs solid SMNs later) and treatment-era drivers (radiation, GVHD, immune suppression)

SOT: Solid organ transplantation; HSCT: Hematopoietic stem cell transplantation; ESRD: End-stage renal disease; SIR: Standardized incidence ratio; NHL: Non-Hodgkin lymphoma; PTLD: Post-transplant lymphoproliferative disease; EBV: Epstein-Barr virus; aHR: Adjusted hazard ratio; HR: Hazard ratio; IRR: Incidence rate ratio; SMNs: Solid malignant neoplasms; GVHD: Graft-vs-host disease.