CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced i

•CD56 enriched donor cell infusion without CD3 depletion is feasible as early as day+7 following PTCy based reduced intensity haploidentical HSCT with cyclosporine alone as GVHD prophylaxis.•This is associated with a low incidence of acute GVHD, viral reactivation and non-relapse mortality.•The reconstitution of lymphocyte subsets was marked by an early and rapid surge of mature NK cells as well as CD4+ T cells and regulatory T cells (Tregs) compared to myeloablative PTCy based haploidentical HSCT with cyclosporine and mycophenolate as GVHD prophylaxis.•Following CD56 enriched donor cell infusion KIR of donor phenotype reconstituted as early as day +30 with expression of CD56dimCD16+NKG2A−KIR+ phenotype in the study group.

We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4+ T cells and regulatory T cells (Tregs) was noted compared with the control group. KIR of donor phenotype reconstituted as early as day 30 with expression of CD56dimCD16+NKG2A−KIR+ phenotype. None experienced viral or fungal infections, and non-relapse mortality was 10% only. The incidence of grade 2-4 acute GVHD was 50% in the control group with none in the CD56 group (P = 0.01). Only two had de novo chronic GVHD in each group. Relapse occurred in five patients in CD56 group with a median follow-up of 12 months, similar to the control group. Our preliminary data show that CD56+ donor cell infusion after PTCy and short-course cyclosporine is feasible with prompt engraftment, rapid reconstitution of CD4+T cells, Tregs and NK cells and reduced incidence of acute GVHD.

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