Interleukin-10-592 polymorphism: impact on relapse and survival after allogeneic hematopoietic stem cell transplantation in children with hematological malignancies

Laura Schwenk,Susan Wittig,Bernd Gruhn

doi:10.1007/s00432-021-03695-3

Laura Schwenk, Susan Wittig + Show 1 more

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https://doi.org/10.1007/s00432-021-03695-3

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Abstract

PurposeInterleukin-10 (IL-10) potentially can promote the development of alloimmunity. The aim of this study was to investigate if the IL-10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT) and if that has an impact on event-free survival (EFS) and overall survival (OS).MethodsA cohort of 211 children with acute lymphoblastic leukemia (n = 99), acute myeloid leukemia (n = 69), myelodysplastic syndrome (n = 31) or chronic myeloid leukemia (n = 12) who underwent hematopoietic stem cell transplantation (HSCT) in a single center and their respective donors were genotyped of IL-10 gene for rs1800872 using TaqMan real-time polymerase chain reaction.ResultsThe IL-10-592 CC genotype was detected in 107 of the 211 donors (50.7%) and in 106 of the 211 patients (50.2%). Genotype AC was found in 95 donors (45.0%) and in 90 patients (42.7%). Nine donors (4.3%) and 15 patients (7.1%) were homozygous for AA. Ultimately, we observed a significantly reduced incidence of relapse rate (RR) in patients who were transplanted from a donor with the IL-10-592 CC genotype (19% versus 43% (AC) versus 49% (AA); P = 0.0007). In addition, a significant increase of EFS (P = 0.004) and OS (P = 0.006) was detected if the IL-10-592 CC genotype is present in the donor. The occurrence of the IL-10-592 CC genotype, in either donors or recipients, had no significant impact on acute and chronic graft-versus-host disease. In addition, the IL-10-592 genotype of the recipients was not relevant for the RR (P = 0.47434), the EFS (P = 0.840), and the OS (P = 0.535).ConclusionThe IL-10-592 CC genotype in the donor was associated with a significant decrease of RR which led to a significant increase of EFS and OS after HSCT. This is the first study to describe an association of the IL-10 gene polymorphism with RR, EFS, and OS after HSCT. Selecting a donor with the IL-10-592 CC genotype could be a useful therapeutic strategy for improving the outcome after allogeneic HSCT.

Highlights

Leukemia is the most common malignant disease in childhood
19% of the patients who received a transplant from a donor with genotype CC suffered from relapse compared to 43% or 49% of patients who received a transplant from a donor with genotype AC or AA, respectively (P = 0.0007; Fig. 1)
This retrospective study demonstrates that IL-10-592 polymorphism CC of the donor had a significant impact on the relapse rate (RR) (P = 0.0007), the event-free survival (EFS) (P = 0.004) and the overall survival (OS) (P = 0.006)

Summary

Introduction

Leukemia is the most common malignant disease in childhood. The majority of patients with leukemia are cured by means of chemotherapy. High-risk patients with a greater risk of relapse or patients with high-risk relapse require a more intensive therapy. Journal of Cancer Research and Clinical Oncology produced by type 2T-helper cells (Fiorentino et al 1989). IL-10 inhibits the secretion of cytokines of type 1T-helper cells (Fiorentino et al 2016). In addition to the type 2T-helper cells, IL-10 is produced by multiple other cell types, including monocytes, B cells, dendritic cells (Sabat et al 2010), keratinocytes (Enk and Katz 1992), and tumor cells (Asadullah et al 2000)

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