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

GND
1287046363
Affiliation
Department of Pediatrics, Jena University Hospital
Schwenk, Laura;
GND
1312672579
Affiliation
Department of Pediatrics, Jena University Hospital
Wittig, Susan;
GND
11259901X
ORCID
0000-0003-1862-0075
Affiliation
Department of Pediatrics, Jena University Hospital
Gruhn, Bernd

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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