Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.

Incidence of acute and chronic graft-versus-host disease and donor T-cell chimerism after small bowel or combined organ transplantation.

PURPOSE: Graft-versus-host disease (GVHD) after organ transplantation is a rare but life-threatening complication with very high mortality. METHODS: A retrospective review was performed of all patients undergoing small bowel or combined organ transplantation at a single institution during 2003 to 2009. Patients with donor T-cell chimerism were analyzed in detail for development of GVHD. RESULTS: Thirty-two patients were included in the study. Of 32 patients, 11 (34%) had donor T-cell chimerism (range, 0%-53%) studies performed; 7 (64%) of those 11 patients demonstrated clinical features of GVHD. All patients who demonstrated GVHD had detectable donor T-cell chimerism. All patients with GVHD presented with skin involvement. Graft-versus-host disease responded to increased immune suppression therapy. Mortality was 43% (3/7) among patients with GVHD and was caused by multiorgan failure and sepsis in all cases. CONCLUSION: Acute and chronic GVHD were observed frequently after combined solid organ transplantation and were associated with significant mortality and morbidity. Alloreactive donor T cells cotransplanted with the organ likely play a role in the pathophysiology because levels of donor-derived T-cell chimerism correlated with the clinical course of GVHD.