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Stem cell transplantation

Outcomes of UCB transplantation are comparable in FLT3+ AML: results of CIBMTR, EUROCORD and EBMT collaborative analysis

Leukemia volume 31, pages 1408–1414 (2017)Cite this article

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Abstract

Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FMS-like tyrosine kinase 3+ (FLT3+) acute myeloid leukemia (AML), which has poor prognosis because of high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126) (hazard ratio (HR) 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2.32, P=0.02), but not vs URD (HR 1.72, P=0.07). All three cohorts had statistically nonsignificant 3-year LFS: 39% (95% confidence interval (CI): 30–47) after UCB, 43% (95% CI: 30–54) after sibling and 50% (95% CI: 40–60) after URD. Chronic graft-versus-host disease rates were significantly lower after UCB compared with either sibling (HR 0.59, P=0.03) or URD (HR 0.49, P=0.001). Adverse factors for LFS included high leukocyte count at diagnosis and HCT during CR2 (second CR). UCB is a suitable option for adults with FLT3+ AML in the absence of an human leukocyte antigen-matched sibling and its immediate availability may be particularly important for FLT3+ AML where early relapse is common, thus allowing HCT in CR1 (first CR) when outcomes are best.

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Acknowledgements

The CIBMTR is supported 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 Alexion; *Amgen Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Be the Match Foundation; *Bluebird Bio Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cellular Dynamics International Inc.; *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 and 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 US Government.

*Corporate Members.

Author contributions

Additional contributing coauthors: Ravi Vij, Bipin N Savani, James Foran, Ulrike Bacher, Ann Jakubowski, Betty Hamilton, Michael Grunwald, Saar Gill, Mark Hertzberg, Samer Al-Homsi, Ghada Abusin, Bruce Camitta, Mitchell Cairo, Richard Olsson, Ran Reshef, Ayman Saad, Sahara Chhabra, David Rizzieri, Miguel A Diaz, Mohammed Mir, Cesar Freytes, Rammurti Kamble, Zachariah Defilipp, Taiga Nishihori, Marlise Luskin Sachiko Seo, Mona Wirk, Patrick Stiff, Gary Schiller, Muthalagu Ramanathan, Mahmoud Aljurf, Sid Ganguly, Veronika Bachanova, Nelson Chao, Peter Wiernik, Selina Luger, Mary Laughin, Jean Khoury, Saber Wael, Robert P Gale, Mark Litzow and Hillard Lazarus.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Oncology and Transplantation, University of Minnesota Medical Center, Minneapolis, MN, USA

    C Ustun

  2. Service d’Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France

    F Giannotti & A Ruggeri

  3. Eurocord, APHP, University Paris Diderot, Hôpital Saint Louis, Paris, France

    F Giannotti, E Gluckman & A Ruggeri

  4. Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplantation), Medical College of Wisconsin, Milwaukee, WI, USA

    M-J Zhang, H-L Wang & M Eapen

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

    M-J Zhang

  6. University of Minnesota Medical Center Fairview, Minneapolis, MN, USA

    C Brunstein

  7. European Group for Blood and Marrow Transplantation, Leiden, The Netherlands

    M Labopin

  8. Sorbonne Universites, Centre de Recherche (CDR), Saint Antoine, Paris, France

    M Labopin

  9. Churchill Hospital, Oxford, UK

    V Rocha

  10. Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA

    M de Lima

  11. Centre Hospitalier Universitaire de LiFge, Domaine Universityaire du Sart Tilman, Leige, Belgium

    F Baron

  12. Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    B M Sandmaier

  13. Monacord, Centre Scientifique de Monaco, Monaco

    E Gluckman

  14. The Bone Marrow Transplantation Department, Division of Internal Medicine, The Chaim Sheba Medical Center, Ramat-Gan, Israel

    A Nagler

  15. Sheba Cord Blood Bank, Rama-Gan, Israel

    A Nagler

  16. Division of Hematology, Department of Medicine, Oncology and Transplantation, University of Minnesota Medical Center, Minneapolis, MN, USA

    D J Weisdorf

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Ustun, C., Giannotti, F., Zhang, MJ. et al. Outcomes of UCB transplantation are comparable in FLT3+ AML: results of CIBMTR, EUROCORD and EBMT collaborative analysis. Leukemia 31, 1408–1414 (2017). https://doi.org/10.1038/leu.2017.42

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