Aim: Haematopoietic Stem Cell Transplantation (HSCT) is a well-established curative therapy for hematologic malignancies including Acute Myeloid leukemia (AML). Post transplantation, the natural Killer (NK) cells are the first reconstituting lymphocytes. Alloreactive NK cell mediate beneficial effects after HSCT via interaction between donor KIR receptors recipient HLA molecules. The present study was undertaken to understand how HLA-KIR interaction and KIR+NK cells reconstitution impact the HLA-haploidentical transplant outcomes.
Methods: AML patients undergoing Haploidentical HSCT were enrolled. HLA and KIR genotyping was carried out using molecular methods. The NK cells were immunophenotyped by ten-colour flow cytometry.
Results: Among the haploidentical donors, 30% were siblings and 70% were parents. Prior to HSCT, the CMV IgG serology revealed that 50% of the patients had a high risk CMV. Around 60% of the donor/recipient pairs, we observed he ABO blood group compatibility. The neutrophils and platelets engraftment was achieved between day 11-23 in all the recipients. The KIR relevant HLA alleles were observed with a reasonable frequency, i.e HLA-A*03, A*11(23.5% each), HLA B*44 (15%) and the HLA-C locus, the C1 type C*07 (36%) and C*03(13.9%). In majority of patients KIR genotype -AB was the commonest and the KIR B content score of 1 and 2 was observed . Around 40% of the recipients had KIR/HLA ligands compatibility, whereas 60% of the recipients had inhibitory KIR receptors incompatibilities (for KIR2DL1 & amp; 3DL1). Maximum expression of inhibitory KIRs-3DL1 and 2DL1was observed post transplant, whereas 2DL3 expression was low. However, expression of activating receptor KIR 2DS4 was minimal. Majority of patients with KIR/HLA incompatibility did not manifest GVHD.
Conclusion: We observed some interesting leads, however the results did not achieve statistical significance, possibly due to small sample size. This is an ongoing study and several recipient-donors are enrolled, so we intend to analyse a larger cohort soon. Based on the preliminary findings, we expect to observe and present many clinically relevant findings .
