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Late cardiovascular morbidity and mortality following pediatric allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 53, pages 1278–1287 (2018)Cite this article

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Abstract

We analyzed late cardiovascular outcomes of 661 patients who survived at least 2 years from hematopoietic cell transplantation for childhood hematologic malignancy between 1995 and 2008. Center for International Blood and Marrow Transplant Research data was supplemented with surveys focused on cardiotoxicity and potential risk factors. The median duration of follow-up was 97 months (range 24–230). 4.2% of survivors experienced at least one of the primary outcomes including coronary artery disease (0.2%), cerebrovascular accident (0.6%), cardiomyopathy (3%), and cardiac-related death (0.5%). Patients who received anthracycline chemotherapy (HR 4.67, p = 0.036) or cranial or chest radiation (HR 5.58, p < 0.0001; HR 2.18, p = 0.0087) were at increased risk for developing one of the primary outcomes. Dyslipidemia was diagnosed in 18% of survivors. Pre-transplant anthracycline (HR 1.74, p < 0.0001) and chest radiation (HR 1.34, p = 0.0371) were risk factors for dyslipidemia. Overweight/obese body mass status was present in 63% of patients at baseline, 65% at 2 years, and 52% at most recent evaluation. Diabetes was diagnosed in 7% of subjects. In conclusion, severe cardiovascular complications were infrequently reported. The incidence of risk factors including obesity and dyslipidemia were significant and will likely increase the risk of cardiovascular disease over time in transplant survivors.

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Acknowledgements

This study was sponsored by the Jeff Gordon Children’s Foundation and the Pediatric Blood and Marrow Transplant Consortium.

CIBMTR Support List

The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 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 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; Be the Match Foundation; *Bluebird Bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cellular Dynamics International, Inc.; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; Gilead Sciences, Inc.; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children’s Foundation; The Leukemia & Lymphoma Society; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd.—Japan; PCORI; Perkin Elmer, Inc.; Pfizer, Inc.; *Sanofi US; *Seattle Genetics; *Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; University of Minnesota; 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, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.

*Corporate members. Subsequent to this work Dr. Dietz became employed by bluebird bio, Inc, which has provided no support or oversight for the project.

Author contributions

The study was designed by CND, RB, MAP, KSB, BS, NM. Data analysis was performed by JH and RB, and data interpretation by CND, RB, JH, BES, MAP, KSB. The manuscript was written by CND, RB, JH, BES, MAP, KSB. CND, KB, AD, CCD, RG, DAJ, MK, PLM, ERN, JT, MAP, KSB participated in data collection and review. All of the authors participated in reviewing and approving the protocol and manuscript.

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Author notes

  1. These authors contributed equally: Michael A. Pulsipher, K. Scott Baker.

Authors and Affiliations

  1. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA

    Christine N. Duncan

  2. Center of International Blood and Marrow Transplant Research, Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA

    Ruta Brazauskas

  3. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA

    Ruta Brazauskas, Jiaxing Huang & Bronwen E. Shaw

  4. Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Navneet S. Majhail

  5. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin N. Savani

  6. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Mary E. D. Flowers & K. Scott Baker

  7. National Institutes of Health Clinical Center, Bethesda, MD, USA

    Minoo Battiwalla

  8. Phoenix Children’s Center for Cancer and Blood Disorders, Phoenix, AZ, USA

    Kristen Beebe

  9. Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Andrew C. Dietz & Michael A. Pulsipher

  10. Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, USA

    Christopher C. Dvorak

  11. University of Colorado Cancer Center, Aurora, CO, USA

    Roger Giller & Brandon Nuechterlein

  12. Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children’s National Health System, Washington, DC, USA

    David A. Jacobsohn

  13. Division of Hematology, Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Morris Kletzel

  14. Pediatric Division of Blood and Marrow Transplantation, Duke School of Medicine, Durham, NC, USA

    Paul L. Martin

  15. Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA

    Eneida R. Nemecek

  16. Department of Pediatric Hematology Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Julie-An Talano

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  1. Christine N. Duncan
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  2. Ruta Brazauskas
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Correspondence to Christine N. Duncan.

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Duncan, C.N., Brazauskas, R., Huang, J. et al. Late cardiovascular morbidity and mortality following pediatric allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 53, 1278–1287 (2018). https://doi.org/10.1038/s41409-018-0155-z

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