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Lymphoma in Pediatric-Onset Inflammatory Bowel Disease Treated with Infliximab Monotherapy: A Case Series

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Abstract

Background

Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma.

Methods

Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained.

Results

Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein–Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively.

Conclusions

This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.

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Acknowledgments

This work received no specific Grant from any funding agency in the public, commercial or not-for-profit sectors. HSW receives philanthropic support from Martin Schlaff, James Brooks, and the B. Hasso Family Foundation.

Funding

Dr. Konstantinos Papamichael received a lecture fee from Mitsubishi Tannabe Pharma. Dr. Adam S. Cheifetz serves a consultant for AbbVie, Janssen Takeda, Prometheus, Pfizer, Arena, Samsung and Alfasigma; receives research support from Miraca. Dr. Matthew J. Hamilton serves as an advisory board member for Takeda and Pfizer; receives research support from GlaxoSmithKline; and an educational grant from AbbVie and Takeda. In the past three years, Dr. Harland S. Winter has served as an advisory board member and/or consultant for Avaxia, Crestovo, Janssen, Nestle, Pediatric IBD Foundation; has received royalties for UpToDate; has received research grants to MGH from AbbVie, Autism Research Foundation, Janssen, Nestle Nutrition, Scipher, Nutricia and the Pediatric IBD Foundation.

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Authors and Affiliations

  1. Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, CRPZ 5-560, 175 Cambridge Street, Boston, MA, 02114, USA

    Alejandro Llanos-Chea, Logan Jerger, Alison M. Friedmann & Harland S. Winter

  2. Harvard Medical School, CRPZ 5-560, 175 Cambridge Street, Boston, MA, 02114, USA

    Alejandro Llanos-Chea, Logan Jerger, Alison M. Friedmann & Harland S. Winter

  3. Division of Pediatric Gastroenterology, Nutrition, and Liver Diseases, Hasbro Children’s Hospital and Rhode Island Hospital, Hasbro Lower Level, 593 Eddy St., Providence, RI, 02903, USA

    Jason M. Shapiro, Timothy Menz & Meghan Gibson

  4. Warren Alpert Medical School of Brown University, Hasbro Lower Level, 593 Eddy St., Providence, RI, 02903, USA

    Jason M. Shapiro, Timothy Menz & Meghan Gibson

  5. Division of Gastroenterology, Brigham and Women’s Hospital, Crohn’s and Colitis Center, 75 Francis Street, Boston, MA, 02115, USA

    Rachel W. Winter, Sonia Friedman & Matthew J. Hamilton

  6. Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Rachel W. Winter, Sonia Friedman & Matthew J. Hamilton

  7. Department of Pathology, Rhode Island Hospital, The Miriam Hospital, Brown University, Box G-E5, Providence, RI, 02912, USA

    Diana Treaba

  8. Warren Alpert Medical School of Brown University, Brown University, Box G-E5, Providence, RI, 02912, USA

    Diana Treaba

  9. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Beth Israel Deaconess Med Ctr., 330 Brookline Avenue, Rabb Rose 1, Boston, MA, 02215, USA

    Konstantinos Papamichael & Adam S. Cheifetz

  10. Harvard Medical School, Beth Israel Deaconess Med Ctr., 330 Brookline Avenue, Rabb Rose 1, Boston, MA, 02215, USA

    Konstantinos Papamichael & Adam S. Cheifetz

Authors
  1. Alejandro Llanos-Chea
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  2. Jason M. Shapiro
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  3. Rachel W. Winter
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  4. Logan Jerger
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  7. Alison M. Friedmann
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  8. Diana Treaba
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  9. Konstantinos Papamichael
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  10. Adam S. Cheifetz
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  11. Sonia Friedman
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  12. Matthew J. Hamilton
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  13. Harland S. Winter
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Corresponding author

Correspondence to Harland S. Winter.

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Conflict of interest

Dr. Alejandro Llanos-Chea, Dr. Jason M. Shapiro, Dr. Rachel W. Winter, Dr. Logan Jerger, Dr. Timothy Menz, Dr. Meghan Gibson, Dr. Alison M. Friedmann, Dr. Diana Treaba and Dr. Sonia Friedman have no relevant conflict of interest.

Ethical approval

Institutional Review Board approval from Partners Healthcare (Protocol ID#: 2018P000872) and Rhode Island Hospital/The Miriam Hospital (IRB Registration #s: RIH IRB 1-00,000,396, RIH IRB 2-00,004,624, TMH IRB-00,000,482) was obtained.

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Llanos-Chea, A., Shapiro, J.M., Winter, R.W. et al. Lymphoma in Pediatric-Onset Inflammatory Bowel Disease Treated with Infliximab Monotherapy: A Case Series. Dig Dis Sci 67, 252–258 (2022). https://doi.org/10.1007/s10620-021-06884-9

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  • DOI: https://doi.org/10.1007/s10620-021-06884-9

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