Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating Factor-Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and Outcome for T Cell-Replete Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study.

We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell-replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10 × 106/kg CD34+ hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF + Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34+ HSCs on day 4 in the G-CSF + Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P = .0001), PB CD34+ HSC count (median 136 versus 139 cells/µL) on day 5 as well as that in the graft (2.7 versus 2.3 × 106/mL, P = .1) were comparable between the 2 groups. The total nucleated cell count was higher (3.4 versus 3.1 × 108/mL, P = .05), but CD4+ T cells (2.3 versus 2.7 × 107/mL, P = .09) were lower in the G-CSF group with mobilization of regulatory T cells being similar. NK cells were skewed toward the CD56+/16- subset in both groups, varying significantly from the steady-state NK subset ratio in PB. The time to engraftment, incidences of acute and chronic graft-versus-host disease, nonrelapse mortality, and overall survival were also similar. Addition of single-dose Px to G-CSF mobilization improves CD34 recovery and does not significantly alter the T and NK cell composition of the graft, including regulatory T cells, with no adverse impact on transplant outcomes.

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 incidence of acute graft versus host disease: A pilot study.

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.