PB2332 NK‐CELLS REGENERATION AS A PART OF IMMUNOLOGICAL REGENERATION AFTER AUTOLOGOUS STEM CELLS TRANSPLANTATION
Authors: Gartcheva L. , Guenova M. , Ganeva P. , Arnaudov G. , Spassov B. 
Published: June 2019

Background:

Natural killer (NK) cells have gained increasing focus in the field of stem cells transplantation, with a number of discoveries that NK cells can play critical roles in immune responses, e.g. by mediating graft‐versus‐malignancy (GVM) responses.

Aims:

The study was conducted with the aim to monitoring and analyze the dynamics of NK‐cell population reconstruction after autologous stem cells transplantation.

Methods:

Samples from 58 patients (27 male and 31 female) with median age 31.4 years (14‐58) as well as 28 age‐matched control samples were studied by a lymphoid oriented panel of antibodies and flow cytometry in nine different points for a period of 24 months. The absolute count (AC) and % of NK‐cells were determined. The group included patients with lymphoma (n = 32); leukemia (n = 7); solid tumors (n = 12) and multiple myeloma (n = 7). According to the disease status at transplantation, 17 patients were in complete response (CR) and very good partial response (VGPR), 31 in PR and 10 in progression.

Results:

The mean AC of CD56+ NK‐cells was 314 cells/μl in the control group (p5 ‐ 164 cells/μl; p95 ‐ 718 cells/μl) and the mean % was 14% (p5 ‐ 7%; p95 ‐ 26%). In general, patients’ levels of CD56+ NK‐cells (% and AC) before ASCT were low, around the p5 values (mean 10.76% and AC 102.78 cells/μl). The % values increased after +2 month (mean 12.387%), however, values approached the mean values of the control group at +24 month. No significant correlation was found between the level of hematological reconstitution and NK‐cells (% and AC). The AC NK‐cells 30 days after ASCT statistically correlated with CD19+ B‐cells reconstitution (r = 0.3465; p<0.05). As a whole, regardless of the fluctuations, the % NK‐cells remained below the control average but within the range of p5‐p95 in patients >20 years of age, while in patients <20 years the % remained closer to the lower limit during the entire period. The recovery of the AC showed similar dynamics in all age groups and after +18 month remained below p5 only in the group < 20 years. According to the diagnosis, only patients with solid tumors demonstrated higher % values before the ASCT (mean 14.16%), while after the transplantation all except myeloma patients showed recovery within the control ranges. Certain differences in the recovery dynamics were observed according to the disease status at transplantation. In patients, transplanted in CR and VGPR, after the decrease (mean 8.23 ± 6.05% and AC 58.96 ± 61.045 cells/μl) at +1 month, values showed a sharp increase at +2 month (mean 12.23 ± 8.26% and AC 110.709 ± 8.727cells/μl). The same was found in patients transplanted in progression (from mean 7.37 ± 6.69% and AC 34.913 ± 53.145 cells/μl to mean 8.31 ± 2.63% and AC 104.106 ± 57.117 cells/μl). In patients with PR, the lowest levels were recorded at +3 month (mean 9.71 ± 5.43% % and AC 101.071 ± 49.973 cells/μl). Further, we compared two conditioning regimens in lymphoma patients: BEAM (n = 15) and LACE (n = 10) and found differences in the recovery after +6 month. The % NK‐cells in the BEAM group decreased from +6 to +9 month and then increased from +18 to +24 month, while in the LACE group there was a sharp decline later from +9 to +18 month and an increase thereafter, however staying within the reference interval throughout the follow‐up period.

Summary/Conclusion:

NK‐cells population showed faster reconstruction after ASCT in comparison to other lymphoid populations. The process of recovery depends more on age‐related factors than on diagnosis, disease status at transplantation or the conditioning therapy.