Role of Donor Activating KIR–HLA Ligand–Mediated NK Cell Education Status in Control of Malignancy in Hematopoietic Cell Transplant Recipients

AbstractSome cancers treated with allogeneic hematopoietic stem cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR (aKIR)-based HLA I–dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression-free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70; P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020, Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096, Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and TTP were significantly dependent on the number of aKIR-based education systems in donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr = .038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P = .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high numbers of aKIR-HLA-based education systems, especially for recipients with missing cognate ligand, is advisable

sj-docx-1-opp-10.1177_10781552231203371 - Supplemental material for Therapeutic adherence and assessment of satisfaction patients with multiple myeloma treated with immunomodulatory drugs in a “real-world” study: Experiences of the Polish Myeloma Group

Supplemental material, sj-docx-1-opp-10.1177_10781552231203371 for Therapeutic adherence and assessment of satisfaction patients with multiple myeloma treated with immunomodulatory drugs in a “real-world” study: Experiences of the Polish Myeloma Group by Grzegorz Charliński, Norbert Grząśko, Łukasz Bołkun, Waldemar Sawicki, Edyta Paczkowska, Agnieszka Druzd-Sitek, Lidia Usnarska-Zubkiewicz, Aleksandra Butrym, Elżbieta Wiater, Piotr Boguradzki, Bożena Budziszewska, Małgorzata Wojciechowska, Monika Mordak-Domagała and Artur Jurczyszyn in Journal of Oncology Pharmacy Practice</p