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

doi:10.3389/fimmu.2023.1332777

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

Research output: Contribution to journal › Article › peer-review

25 Downloads (Pure)

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 language	English
Article number	1332777
Journal	Frontiers in immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1332777
Publication status	Published - 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

Access to Document

10.3389/fimmu.2023.1332777Licence: Creative Commons: Attribution (CC BY)

VermaK2024EarlyFinal published version, 7.38 MBLicence: Creative Commons: Attribution (CC BY)

The T cell immune response to cytomegalovirus across the adult lifecourse
Moss, P. & Zuo, J.
Medical Research Council
31/10/18 → 31/10/24
Project: Research

Cite this

@article{c4402f30bfe94876b8778883be34fb72,

title = "Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation",

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.",

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

author = "Kriti Verma and Wayne Croft and David Greenwood and Christine Stephens and Ram Malladi and Jane Nunnick and Jianmin Zuo and Kinsella, {Francesca A M} and Paul Moss",

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 {\textcopyright} 2024 Verma, Croft, Greenwood, Stephens, Malladi, Nunnick, Zuo, Kinsella and Moss.",

year = "2024",

month = jan,

day = "3",

doi = "10.3389/fimmu.2023.1332777",

language = "English",

volume = "14",

journal = "Frontiers in immunology",

issn = "1664-3224",

publisher = "Frontiers",

}

TY - JOUR

T1 - Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation

AU - Verma, Kriti

AU - Croft, Wayne

AU - Greenwood, David

AU - Stephens, Christine

AU - Malladi, Ram

AU - Nunnick, Jane

AU - Zuo, Jianmin

AU - Kinsella, Francesca A M

AU - Moss, Paul

N1 - 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.

PY - 2024/1/3

Y1 - 2024/1/3

N2 - 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.

AB - 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.

KW - Humans

KW - Prognosis

KW - Transplantation, Homologous/adverse effects

KW - Neoplasm Recurrence, Local/complications

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Graft vs Host Disease

KW - Chronic Disease

KW - Recurrence

U2 - 10.3389/fimmu.2023.1332777

DO - 10.3389/fimmu.2023.1332777

M3 - Article

C2 - 38235129

SN - 1664-3224

VL - 14

JO - Frontiers in immunology

JF - Frontiers in immunology

M1 - 1332777

ER -

Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Projects

The T cell immune response to cytomegalovirus across the adult lifecourse

Cite this