Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation

Kriti Verma, Wayne Croft, David Greenwood, Christine Stephens, Ram Malladi, Jane Nunnick, Jianmin Zuo, Francesca A M Kinsella, Paul Moss*

*Corresponding author for this work

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Abstract

Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy although graft versus host disease and relapse remain major complications. We measured the serum protein expression of 92 inflammation-related markers from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation and related values to subsequent clinical outcomes. Low levels of 7 proteins at D0 were linked to GvHD whilst high levels of 7 proteins were associated with relapse. The concentration of 38 proteins increased over 14 days and higher inflammatory response at D14 was strongly correlated with patient age. A marked increment in protein concentration during this period associated with GvHD but reduced risk of disease relapse, indicating a link with alloreactive immunity. In contrast, patients who demonstrated low dynamic elevation of inflammatory markers during the first 14 days were at increased risk of subsequent disease relapse. Multivariate time-to-event analysis revealed that high CCL23 at D14 was associative of AGvHD, CXCL10 with reduced rate of relapse, and high PD-L1 with reduced overall survival. This work identifies a dynamic pattern of inflammatory biomarkers in the very early post-transplantation period and reveals early protein markers that may help to guide patient management.

Original languageEnglish
Article number1332777
JournalFrontiers in immunology
Volume14
DOIs
Publication statusPublished - 3 Jan 2024

Bibliographical note

Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by Blood Cancer UK (grant 17009), NIHR Birmingham Biomedical Research Centre award (NIHR 203326), NIHR senior investigator award (NIHR205029) awarded to PM and MRC Placing Discovery Science at the heart of Big Data (MC_PC_15079). WC is supported by MRC (grant MR/R011230/1). This is independent research funded by Professor PM and carried out at the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the BRC, the NIHR or the Department of Health and Social Care.

Copyright © 2024 Verma, Croft, Greenwood, Stephens, Malladi, Nunnick, Zuo, Kinsella and Moss.

Keywords

  • Humans
  • Prognosis
  • Transplantation, Homologous/adverse effects
  • Neoplasm Recurrence, Local/complications
  • Hematopoietic Stem Cell Transplantation/adverse effects
  • Graft vs Host Disease
  • Chronic Disease
  • Recurrence

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