Background: Natural killer cells (NK) can play a decisive role in preventing early relapses and infectious complications after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) due to their comparatively fast reconstitution after HSCT. And when performing haplo-HSCT with depletion of TCRαβ-positive T-lymphocytes, the graft versus leukemia (GVL) effect is carried out only at the expense of donor NK cells. NK differentiate from immature (CD56bright) to mature (CD56dim) and terminally differentiated. NK differentiation to the subpopulation CD56dimCD16+ is necessary to implement an alloreactive NK cell immune response.
Aims: To study the rate and features of NK cell reconstitution after haplo-HSCT.
Methods: The study included 16 patients with acute myeloid leukemia (AML) and 13 patients with acute lymphoblastic leukemia (ALL) who underwent haplo-HSCT at the National Medical Research Center for Hematology from April 2020 to June 2021. 15 patients - with the use of post-transplant cyclophosphamide (PT-Cy), 14 - with previous TCRαβ-depletion. To assess the reconstitution of NK, all patients underwent immunophenotypic studies of peripheral blood samples at +14, +30, +60, +90 and +180 days after haplo-HSCT using a 12-color flow cytometer (CytoFlex Beckman Coulter, USA). Monoclonal antibodies to human differentiation antigens CD3, CD8, CD158a, CD158b, CD158e, CD159a, CD57, CD16, CD56, CD14, CD45, CD62L were used in the analysis of subpopulations of NK cells. The SAS 9.4 software (Sas institute inc., Cary, NC, USA) was used for statistical data processing. Differences were considered statistically significant at p<0.05.
Results: NK reached a mature immunophenotype faster in the case of haplo-HSCT with TCRαβ-depletion: by day +30 after HSCT, the median proportion of CD56dimCD16+ NK cells with TCRαβ-depletion was 57% versus 9% when using PT-Cy, p= 0.0045. Significant differences persisted up to +60 (74% vs. 41% (p=0.0079)) and +90 days after haplo-HSCT (81% vs. 46% (p=0.0076)) (Fig. 1).
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Summary/Conclusion: The rate of reconstitution and the acquisition of an alloreactive phenotype by NK depends on the variant of T-cell depletion; faster recovery occurs when performing haplo-HSCT with TCRαβ-depletion. When using PT-Cy, the recovery of the mature NK cell population occurs at a later time after haplo-HSCT (from +3 to + 6 months) and such patients may benefit from transfusions of donor NK cells at the post-transplant stage. This approach can be considered as a worthy alternative to donor.