Von Willebrand Factor and Platelet Levels before Conditioning Chemotherapy Indicate Bone Marrow Regeneration following Autologous Hematopoietic Stem Cell Transplantation

  • Zita Radnay
  • , Árpád Illés
  • , Miklós Udvardy
  • , Zoltán Prohászka
  • , György Sinkovits
  • , Mária Csilla Csányi
  • , Miklós Kellermayer
  • , Attila Kiss
  • , Jolán Hársfalvi* (Corresponding Author)
  • *Corresponding author for this work

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Abstract

Autologous hematopoietic stem cell transplantation (HSCT) is often complicated by hemostatic and thrombotic events associated with endothelial cell injury. Thrombotic complications are affected by a disturbed balance between platelets, circulating von Willebrand factor (VWF), and its specific protease, ADAMTS13. HSCT-associated endothelial dysfunction, impaired hemostasis, and inflammation are interrelated processes, and research on the complex interplay of conditioning regimens from engraftment to bone marrow regeneration remains intensive. This prospective observational study comparing lymphoma and multiple myeloma (MM) patients who underwent autologous HSCT explored how platelet count, VWF level, ADAMTS13 activity, and C-reactive protein (CRP) level as potential markers (1) vary in response to therapy, (2) differ between the 2 groups, and (3) correlate with the remission state at 100 days after HSCT. We correlated the quantitative changes in platelet count and levels of VWF, ADAMTS13, and CRP with one another during HSCT and in the remission state in 45 patients with lymphoma and 59 patients with MM who underwent autologous HSCT between 2010 and 2013 at the University of Debrecen. Samples were collected at the start of conditioning chemotherapy, on the day of stem cell transplantation, and at 5, 11, and 100 days following HSCT. CRP levels peaked when platelet counts dropped to a minimum, and these changes were much more pronounced in the lymphoma group. VWF level was the highest, with lower ADAMTS13 activity, at platelet engraftment in both patient groups equally. Diagnostic evidence indicative of thrombotic complications was not found. In the lymphoma group, VWF level prior to conditioning had statistically significant correlations with platelet count, CRP level, and hemoglobin concentration at the time of bone marrow regeneration (P < .001) and during the remission state (P = .034). In the MM group, platelet count before conditioning was correlated with platelet count (P < .001) and white blood cell count (P = .012) at the time of bone marrow regeneration. The statistically significant correlation of the markers at the time of bone marrow regeneration with the preconditioning VWF levels in lymphoma and with the preconditioning platelet counts in MM might indicate the clinical significance of the bone marrow niches of arterioles and megakaryocytes, respectively, where the stem cells are located and regulated. Because preconditioning VWF levels are associated with remission after HSCT in lymphoma patients, VWF should be screened before conditioning, along with the markers used in HSCT protocols, to optimize personalized treatment and reduce therapeutic risks.
Original languageEnglish
Pages (from-to)830.e1-830.e7
Number of pages7
JournalTransplantation and Cellular Therapy
Volume28
Issue number12
Early online date2 Dec 2022
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

The authors thank Katalin Hodosi for help with the statistical analysis, Gergely Agócs and Dániel Veres for critical comments, Ágnes Sándor for technical assistance, and the staff of the Transplantation Unit and the Department of Laboratory Medicine for their valuable contributions to this project. They also thank Hans Deckmyn and János Kappelmayer for proofreading the manuscript.

Funding

This research was supported by the National Research, Development and Innovation Office[HJ1] 2020-4.1.1.-TKP2020, OTKA K-124966 and OTKA K-135360.

Keywords

  • Conditioning and induction therapy
  • hematopoietic stem cell transplantation
  • Autologous stem cell transplantation
  • CD34+ cells
  • Stem cells
  • Endothelial damage
  • Von Willebrand factor
  • ADAMTS13
  • C-reactive protein
  • Platelets
  • Hemoglobin

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