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Pediatric Transplants

Second malignancies after autologous hematopoietic cell transplantation in children

Bone Marrow Transplantation volume 48, pages 363–368 (2013)Cite this article

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Abstract

Childhood autologous hematopoietic cell transplant (auto-HCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1487 pediatric auto-HCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), central nervous system tumors (14%) and Wilms tumor (2%). Median follow-up was 8 years (range, <1–21 years). SMNs were reported in 35 patients (AML/myelodysplastic syndrome (MDS)=13, solid cancers=20, subtype missing=2). The overall cumulative incidence of SMNs at 10 years from auto-HCT was 2.60% (AML/MDS=1.06%, solid tumors=1.30%). We found no association between SMNs risk and age, gender, diagnosis, disease status, time since diagnosis or use of TBI or etoposide as part of conditioning. OS at 5-years from diagnosis of SMNs was 33% (95% confidence interval (CI), 16–52%). When compared with age- and gender-matched general population, auto-HCT recipients had 24 times higher risks of developing SMNs (95% CI, 16.0–33.0). Notable SMN sites included bone (N=5 SMNs, observed (O)/expected (E)=81), thyroid (N=5, O/E=53), breast (N=2, O/E=93), soft tissue (N=2, O/E=34), AML (N=6, O/E=266) and MDS (N=7, O/E=6603). Risks of SMNs increased with longer follow-up from auto-HCT. Pediatric auto-HCT recipients are at considerably increased risk for SMNs and need life-long surveillance for SMNs.

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Acknowledgements

The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children’s Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; the Leukemia and Lymphoma Society; the Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the US Government.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    K E Danner-Koptik, K J Dilley & N Hijiya

  2. Donor Medical Services, National Marrow Donor Program, Minneapolis, MN, USA

    N S Majhail

  3. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    R Brazauskas & Z Wang

  4. Department of Hematology and Bone Marrow Transplant, Children’s Hospital of Orange County, Orange, CA, USA

    D Buchbinder

  5. Department of Hematologie, Hospital A Michallon, CHU de Grenoble, Grenoble, France

    J-Y Cahn

  6. Department of Pediatric Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    H A Frangoul & B N Savani

  7. Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA

    T G Gross

  8. Department of Pediatric Hematology and Oncology, All Children’s Hospital, St Petersburg, FL, USA

    G A Hale

  9. Department of Pediatrics, St Louis Children’s Hospital, Washington University, St Louis, MO, USA

    R J Hayashi

  10. Department of Hematology and Oncology, Baylor College of Medicine Center for Cell and Gene Therapy, Houston, TX, USA

    R T Kamble

  11. Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA

    H M Lazarus

  12. Adult Bone Marrow Transplant Unit, Bristol Children’s Hospital, Bristol, UK

    D I Marks

  13. Department of Medicine, Florida Center for Cellular Therapy, Florida Center for Cellular Therapy, Orlando, FL, USA

    V Reddy

  14. Department of Pediatrics, Uniformed Services University, Bethesda, MD, USA

    A B Warwick

  15. Department of Bone Marrow Transplant, Shands HealthCare and University of Florida, Gainesville, FL, USA

    J R Wingard

  16. Department of Hematology and Oncology, University of North Carolina Hospitals, Chapel Hill, NC, USA

    W A Wood

  17. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M L Sorror

  18. Division of Blood and Marrow Transplantation, Children’s National Medical Center, Washington, DC, USA

    D A Jacobsohn

Authors
  1. K E Danner-Koptik
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  2. N S Majhail
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  3. R Brazauskas
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  4. Z Wang
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  5. D Buchbinder
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  6. J-Y Cahn
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  7. K J Dilley
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  8. H A Frangoul
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  9. T G Gross
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  10. G A Hale
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  11. R J Hayashi
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  12. N Hijiya
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  13. R T Kamble
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  14. H M Lazarus
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  15. D I Marks
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  16. V Reddy
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  17. B N Savani
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  18. A B Warwick
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  19. J R Wingard
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  20. W A Wood
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  21. M L Sorror
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  22. D A Jacobsohn
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Corresponding author

Correspondence to N S Majhail.

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Danner-Koptik, K., Majhail, N., Brazauskas, R. et al. Second malignancies after autologous hematopoietic cell transplantation in children. Bone Marrow Transplant 48, 363–368 (2013). https://doi.org/10.1038/bmt.2012.166

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  • DOI: https://doi.org/10.1038/bmt.2012.166

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