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Acute Leukemia

YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

Bone Marrow Transplantation volume 51, pages 1556–1560 (2016)Cite this article

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Abstract

YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were no significant associations between plasma YKL-40 concentrations in recipients and any outcome measures. In donors with YKL-40 plasma concentrations above the age-adjusted 95th percentile, a trend toward increased grade II–IV acute GvHD in recipients was observed (adjusted hazard ratio 1.39 (95% confidence interval 1.00–1.94), P=0.050), with no significant associations with overall survival, treatment-related mortality or relapse. In conclusion, our study shows that YKL-40 does not aid risk stratification of patients undergoing allogeneic HCT, but suggests that YKL-40 may aid donor selection when multiple, otherwise equal, donors are available.

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Acknowledgements

The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-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 N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc.; GentiumSpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children’s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St Baldrick’s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; TarixPharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; 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 US Government. The study was also supported by grants from the Danish Biotechnology Program, the Danish Child Cancer Foundation and the Dagmar Marshall Foundation.

Author contributions

BK designed the study, analyzed and interpreted data, and drafted and revised the manuscript. TW, XZ, SRS, MF, CM, MRV and SJL provided patient and donor material, performed statistical analyses, interpreted data and revised the manuscript. JSJ performed plasma YKL-40 measurements, interpreted data and revised the manuscript. KM, LV and PG planned and designed the study, interpreted data and revised the manuscript.

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Authors and Affiliations

  1. Department of Hematology, The Allogeneic Hematopoietic Cell Transplantation Laboratory, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    B Kornblit & L Vindelov

  2. Division of Biostatistics, Institute for Health & Society, Medical College of Wisconsin, Milwaukee, WI, USA

    T Wang

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

    T Wang & X Zhu

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

    S J Lee

  5. Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA

    S J Lee & S R Spellman

  6. Institute for Experimental Cellular Therapy, Universitatsklinikum Essen KMT, Essen, Germany

    K Fleischhauer

  7. Zentrales Knochenmarkspender-Register Deutschland, Ulm, Germany

    C Müller

  8. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    M R Verneris

  9. Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    K Müller

  10. Department of Oncology and Medicine, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    J S Johansen

  11. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    J S Johansen & P Garred

  12. Department of Clinical Immunology - Section 7631, Laboratory of Molecular Medicine,

    P Garred

  13. Rigshospitalet, Copenhagen, Denmark

    P Garred

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  1. B Kornblit
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Corresponding author

Correspondence to B Kornblit.

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Kornblit, B., Wang, T., Lee, S. et al. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome. Bone Marrow Transplant 51, 1556–1560 (2016). https://doi.org/10.1038/bmt.2016.192

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  • DOI: https://doi.org/10.1038/bmt.2016.192

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