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Endogenous thrombopoietin levels are elevated following double cord blood unit transplantation

Bone Marrow Transplantation volume 55, pages 1178–1180 (2020)Cite this article

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Recovery of hematopoiesis following allogeneic hematopoietic cell transplantation (HCT) is dependent of a number of clinical factors, including graft source. Specifically, platelet engraftment is delayed after umbilical cord blood (UCB) transplantation, with a median time to platelet count > 20 × 109/L of 52 days [1]. Prolonged thrombocytopenia may increase transfusion requirements and the risk for bleeding, which may contribute to morbidity, poor quality of life, and cost after UCB transplantation. Two thrombopoietin (TPO) receptor agonists, romiplostim and eltrombopag, have demonstrated the ability to increase platelet counts in conditions with prolonged thrombocytopenia, including immune thrombocytopenia and severe aplastic anemia, and have been used after allogeneic HCT in few reports [2,3,4,5,6,7]. We conducted a correlative study to assess TPO levels prior to and after double UCB transplantation to guide further investigation of TPO receptor agonists for treating prolonged thrombocytopenia after allogeneic HCT.

We treated 31 subjects in a phase II study of reduced-intensity double UCB transplantation using fludarabine, melphalan, and low-dose total body irradiation (NCT01408563). This study was approved by the institutional review board at the Dana-Farber Harvard Cancer Center and conducted at Dana-Farber Brigham and Women’s Cancer Center, Massachusetts General Hospital Cancer Center and Beth Israel Deaconess Medical Center. Informed consent was obtained from all patients. Twenty subjects enrolled in the optional TPO correlative investigation. The median age was 58 years (range, 21–68). Fourteen subjects were male and six were female. The median combined total nucleated cells of the infused cord units (post-thaw) was 4.1 × 107 TNC/kg (range, 2.9–6.2). The median combined number of CD34+ cells of the infused cord units (post-thaw) was 1.6 × 105 CD34+/kg (range, 0.6–3.5). One subject experience primary graft failure. Nineteen subjects achieved neutrophil engraftment (first of three consecutive days with absolute neutrophil count > 500) at a median of 25 days (range, 13–54) after transplant.

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Acknowledgements

Amgen Inc. provided clinical trial funding.

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Authors and Affiliations

  1. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA, USA

    Zachariah DeFilipp, Jami Brown & Yi-Bin Chen

  2. Blood Transfusion Service, Massachusetts General Hospital, Boston, MA, USA

    Robert S. Makar

  3. Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    David Avigan

  4. Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA

    Corey S. Cutler

  5. Division of Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Karen K. Ballen

  6. Division of Hematology, Massachusetts General Hospital, Boston, MA, United States

    David J. Kuter

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  1. Zachariah DeFilipp
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Correspondence to Zachariah DeFilipp.

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Conflict of interest

ZD reports research funding from Incyte, Corp. DJK reports research funding (Protalex, Bristol-Myers Squibb, Rigel, Bioverativ, Agios, Syntimmune, Principia, Alnylam) and consultancy (ONO, Pfizer, 3SBios, Eisai, GlaxoSmithKline, Genzyme, Shire, Alexion, Amgen, Shionogi, Rigel, Syntimmune, MedImmune, Novartis, Bioverativ, Argenx, Zafgen). All other authors declare no conflict of interest.

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DeFilipp, Z., Makar, R.S., Brown, J. et al. Endogenous thrombopoietin levels are elevated following double cord blood unit transplantation. Bone Marrow Transplant 55, 1178–1180 (2020). https://doi.org/10.1038/s41409-019-0652-8

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