TY - JOUR

T1 - Plasma Levels of MRP-8/14 Associate With Neutrophil Recovery, Bacterial Bloodstream Infections, and Engraftment Syndrome Following Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

AU - Kammersgaard, Marte B.

AU - Kielsen, Katrine

AU - Nielsen, Claus H.

AU - Ifversen, Marianne

AU - Bohr, Anne Helene

AU - Müller, Klaus

N1 - Funding Information: Financial disclosure: Supported by The Research Council at Rigshospitalet ( no. R131-A5521 ) and the Childhood Cancer Foundation ( no. 2019-1 ). Publisher Copyright: © 2023 The American Society for Transplantation and Cellular Therapy

PY - 2023

Y1 - 2023

N2 - Neutrophil engraftment is essential for the successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT), but neutrophil activation may also induce transplant-related complications. Myeloid-related protein (MRP)-8/14 is expressed in granulocytes during inflammatory conditions and secreted in response to tissue damage along with the release of pro-inflammatory cytokines together with leukocyte recruitment and activation. In this study, we investigated associations between levels of the neutrophil activition marker MRP-8/14, neutrophil recovery and toxicities after pediatric HSCT. We included 73 children undergoing allogeneic HSCT using bone marrow or peripheral blood stem cell grafts from matched sibling or unrelated donors. Plasma levels of MRP-8/14 were measured by enzyme-linked immunosorbent assay from preconditioning until 6 months after transplantation. Overall, MRP-8/14 levels decreased from pre-conditioning to a nadir at day 7 and then rose again until day 28, preceding the reappearance of neutrophils. MRP-8/14 levels were significantly reduced at day 14 in patients with delayed neutrophil engraftment compared with patients who engrafted by day 21 (0.20 versus 0.48 μg/mL, P =.0012) and in patients who developed bacterial bloodstream infections compared to patients without this complication (0.2 versus 0.36 μg/mL, P =.048). Patients developing engraftment syndrome had significantly elevated MRP-8/14 levels at day 7 and 21 compared to patients without engraftment syndrome (0.32 versus 0.2 μg/mL, P =.042 and 1.9 versus 0.80 μg/mL, P =.039, respectively), as well as increased neutrophil counts from day 9 to 25 (P ≤.016). Similarly, neutrophil counts were increased at day 13 to 17 in patients with acute graft-versus-host disease grade III-IV compared with grade 0-II. This study is the first to monitor neutrophil activation by MRP-8/14 in HSCT patients in relation to infectious, as well as noninfectious post-transplantation complications. Our results provide increased insights into the pathophysiology of these complications, and further studies should explore the potential use of MRP-8/14 as a clinically useful biomarker.

AB - Neutrophil engraftment is essential for the successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT), but neutrophil activation may also induce transplant-related complications. Myeloid-related protein (MRP)-8/14 is expressed in granulocytes during inflammatory conditions and secreted in response to tissue damage along with the release of pro-inflammatory cytokines together with leukocyte recruitment and activation. In this study, we investigated associations between levels of the neutrophil activition marker MRP-8/14, neutrophil recovery and toxicities after pediatric HSCT. We included 73 children undergoing allogeneic HSCT using bone marrow or peripheral blood stem cell grafts from matched sibling or unrelated donors. Plasma levels of MRP-8/14 were measured by enzyme-linked immunosorbent assay from preconditioning until 6 months after transplantation. Overall, MRP-8/14 levels decreased from pre-conditioning to a nadir at day 7 and then rose again until day 28, preceding the reappearance of neutrophils. MRP-8/14 levels were significantly reduced at day 14 in patients with delayed neutrophil engraftment compared with patients who engrafted by day 21 (0.20 versus 0.48 μg/mL, P =.0012) and in patients who developed bacterial bloodstream infections compared to patients without this complication (0.2 versus 0.36 μg/mL, P =.048). Patients developing engraftment syndrome had significantly elevated MRP-8/14 levels at day 7 and 21 compared to patients without engraftment syndrome (0.32 versus 0.2 μg/mL, P =.042 and 1.9 versus 0.80 μg/mL, P =.039, respectively), as well as increased neutrophil counts from day 9 to 25 (P ≤.016). Similarly, neutrophil counts were increased at day 13 to 17 in patients with acute graft-versus-host disease grade III-IV compared with grade 0-II. This study is the first to monitor neutrophil activation by MRP-8/14 in HSCT patients in relation to infectious, as well as noninfectious post-transplantation complications. Our results provide increased insights into the pathophysiology of these complications, and further studies should explore the potential use of MRP-8/14 as a clinically useful biomarker.

KW - Engraftment syndrome

KW - Hematopoietic stem cell transplantation

KW - Infections

KW - MRP-8/14

KW - Neutrophil engraftment

U2 - 10.1016/j.jtct.2022.12.019

DO - 10.1016/j.jtct.2022.12.019

M3 - Journal article

C2 - 36587741

AN - SCOPUS:85147556487

VL - 29

SP - 242.e1-242.e9

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

SN - 2666-6375

IS - 4

ER -