4.6 Article

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

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 148, Issue 4, Pages 985-991

Publisher

SPRINGER
DOI: 10.1007/s00432-021-03695-3

Keywords

Interleukin 10; Single nucleotide polymorphism; Allogeneic hematopoietic stem cell transplantation; Children; Relapse rate; Event-free survival

Categories

Funding

  1. Projekt DEAL

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The study revealed that the IL-10-592 CC genotype in the donor significantly reduces the relapse rate after hematopoietic stem cell transplantation, leading to an increase in event-free survival and overall survival.
Purpose Interleukin-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). Methods A 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. Results The 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). Conclusion The 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.

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