Elsevier

Cytokine

Volume 153, May 2022, 155869
Cytokine

Prognostic role of serum cytokines and soluble HLA-G levels in children with leukemia who undergo allogeneic stem cell transplantation

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Abstract

This is the first study to have investigated the prognostic role of cytokines and soluble human leukocyte antigen-G (sHLA-G) levels in pediatric leukemia patients who have undergone allogeneic stem cell transplantation (allo-SCT). Forty-one patients with acute leukemia (n = 28, acute lymphoblastic leukemia (ALL) and n = 13, acute myeloblastic leukemia) were recruited. Patients were examined at diagnosis (n = 26), in the pre-transplantation period (PreTx) (n = 26), on the day of transplantation (Tx0) (n = 41), and on post-transplantation Days 14 (PostTx14) (n = 41) and 28 (PostTx28) (n = 41). Serum levels of pro-inflammatory cytokines (interleukin [IL]-1, IL-2, IL-6, Tumor necrosis factor [TNF]-α), anti-inflammatory cytokines (IL-4, IL-10), and sHLA-G were measured by Enzyme-Linked ImmunoSorbent Assay. Median levels of all cytokines tested and sHLA-G were significantly higher at diagnosis and at the post-transplant time points than at PreTx (all p < 0.05). At the time of diagnosis (specifically ALL) and at PostTx14, elevated IL-4, IL-10, and/or sHLA-G were associated with higher post-transplant relapse rates (all p < 0.05). Elevated IL-2 and TNF-α at Tx0 were associated with lower survival rates (both p < 0.05). Levels of serum cytokines and sHLA-G may be useful predictors of survival and relapse in pediatric leukemia patients who undergo allo-SCT.

Introduction

Relapse and transplant-related complications are significant barriers to the success of allogeneic stem cell transplantation (allo-SCT) in children with leukemia [1]. Pathologic immune activation due to uncontrolled cytokine release occurs in patients with relapse and transplant-related complications [2], [3], [4], [5], [6], [7], [8], [9]. Recently, it has been reported that increased level of soluble human leukocyte antigen-G (sHLA-G) by leukemic cells may contribute to relapse [9]. However, it has been reported that elevated sHLA-G level may prevent transplant-related complications during allo-SCT [4]. Few data have been published regarding the role of cytokines and sHLA-G levels in patients with acute leukemia undergoing allo-SCT [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. No study has yet investigated the prognostic role of serum cytokine levels and sHLA-G levels at diagnosis, before and shortly after allo-SCT for pediatric leukemia.

The aim of this study was to investigate the prognostic role of serum cytokine and sHLA-G levels in children with acute leukemia undergoing allo-SCT.

Section snippets

Methods

This prospective longitudinal cohort study was carried out in the Pediatric Hematology Unit of Gazi University, Turkey between 2019 and 2021. The ethics committee approved the study (GO-18/1135). All parents gave informed consent.

Results

The demographic and clinical characteristics of the 41 patients in the study are summarized in Table 1. The patients were 29 boys (70%) and 12 girls (30%), and their median age at Tx0 was 9.1 years (range, 4.7–13.5 years). Of the 41 patients, 28 had ALL (20 with pre–B ALL and eight with T ALL) and 13 had AML. The indications for transplantation were relapse (n = 23, 18 with ALL and five with AML) and high-risk leukemia (n = 18, 10 with ALL and eight with AML). The median neutrophil and platelet

Discussion

In this study, we found that pediatric leukemia patients exhibited major changes in cytokine levels and sHLA-G levels from the time of the first diagnosis to the time of allo-SCT. The literature contains little data regarding the prognostic value of cytokine levels and sHLA-G level in patients with acute leukemia undergoing allo-SCT [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. In the healthy bone marrow, pro-inflammatory and anti-inflammatory cytokines maintain a balance between

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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  • 1

    Professor of Pediatric Hematology, Gazi University Faculty of Medicine, Department of Pediatric Hematology.

    2

    Assistant Professor of Preventive Oncology, Hacettepe University Cancer Institute, Department of Preventive Oncology.

    3

    Assistant Professor of Pediatric Hematology, Gazi University Faculty of Medicine, Department of Pediatric Hematology.

    4

    Professor of Pediatric Hematology, Gazi University Faculty of Medicine, Department of Pediatric Hematology.

    5

    Associate Professor of Basic Oncology, Hacettepe University Cancer Institute, Department of Basic Oncology.

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