The use of donor killer immunoglobulin-like receptor (KIR) in unrelated donor (URD) should not be used in the selection for pediatric patients with leukemia undergoing T-replete transplantation, according to a publication in Blood Advances.

Natural killer–cell activation has repeatedly been linked with KIR function, a family of as many as 15 genes related to various inhibitory and activation functions. Previous work demonstrated that, among pediatric patients undergoing T cell–depleted haploidentical transplantation, KIR ligand mismatch between donor and recipient was linked with lower relapse rates in acute myeloid leukemia (AML), but not in acute lymphoblastic leukemia (ALL). Further, confirmatory studies yielded mixed results.

Researchers evaluated whether any KIR-relevant variables are linked with relapse outcomes among pediatric patients with AML or ALL undergoing T cell–depleted or in vivo T cell–depleted URD transplantation, to assess whether variations in the donor KIR system are linked to improved transplant outcomes.

Overall, 372 patients with ALL and 344 patients with AML were included from 51 and 60 centers, respectively. The median age in the ALL and AML groups were 11 and 12 years, respectively; 61% and 56% of patients were boys; and 82% of patients in both groups had a performance score of 90 to 100. Data for all patients were reported to the Center for International Blood and Marrow Transplant Research between 2005 and 2016, and the median follow-up for ALL and AML patients was 59 months and 54 months, respectively.


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Neither KIR ligand mismatch nor KIR gene content were linked to relapse-free survival or disease-free survival in either the overall cohort or between AML and ALL separately. There was, furthermore, no link found in the in vivo T cell–depleted transplantation group between KIR variables and outcomes.

Some study limitations included the relatively low rate of relapse in children, which might have underpowered the analysis, and the fact that some donor KIR models were interdependent, which may have adjusted data significance.

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“Given these findings, our results do not support the selection of URDs for myeloablative transplantation based on KIR in pediatric patients, as it may lead to a deprioritization of other donor criteria known to be associated with improved outcomes in children,” the authors concluded.

Reference

Verneris MR, Miller JS, Hsu KC, et al. Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia. Blood Adv. 2020;4(7):1350-1356.