344: Effects of preparative regimens on host dendritic cells pre-transplant in allogeneic stem cell transplantation
Biology of Blood and Marrow Transplantation
Host dendritic cells(DCs) present antigens to donor T-cells, thereby initiating graft-vs-host disease (GVHD) in allogeneic stem cell transplantation. The effects of preparative regimens on host DCs remain unknown. We prospectively studied changes in host DC populations pre-transplant. Methods: 17 patients, median age 47 years, with various hematologic malignancies underwent a conventional preparative regimen of cyclophosphamide 120mg/kg and 1200cGy total body irradiation (TBI) (nϭ8) or a
... ) (nϭ8) or a reduced intensity preparative regimen of extracorporeal photopheresis (ECP) x 2 days, pentostatin 8mg/m2 by continuous iv infusion over 48 hours, and 600cGy TBI (nϭ9), followed by allogeneic stem cell transplantation from fully matched related (nϭ7), fully matched unrelated (nϭ9), or 7/8 DR-mismatched unrelated (nϭ1) donors. The Blood Dendritic Cell Enumeration Kit (Miltenyi Biotec, Inc., Auburn, CA) was used to identify the percentages of myeloid DC1 (MDC1), plasmacytoid DC (PDC), and myeloid DC2 (MDC2) subpopulations within the non-B-cell, non-monocytic, non-granulocytic gate in peripheral blood obtained before initiation and after completion of the preparative regimen. Results: The median percentages of MDC1, PDC, and MDC2 cells were as follows: at initiation: 0.26%, 0.11%, and 0.07% respectively, following ECP: 0.38%, 0.07%, and 0.01% respectively, Day 0: 0.07%, 0%, and 0% respectively. Following ECP, the median change in MDC1, PDC, and MDC2 cells were 0%, -58%, and -65% respectively. On Day 0, the median change in MDC1, PDC, and MDC2 cells were -49%, -96%, and -73% respectively among ECP-based regimens, and -98%, -100%, -100% respectively among conventional regimens (pϭ0.73, pϭ0.30, pϭ0.09 respectively). The median ratios of MDC1 to PDC cells were 2.5 pre-transplant, 3.6 following ECP, and 0.56 on Day 0. ECP decreased at least 1 DC lineage by 100% in 50% of patients, but decreased all 3 DC lineages by 100% in only 10% of patients. By Day 0, 76% of patients had at least 1 DC lineage decreased by 100%, and 24% of patients had all 3 DC lineages decrease by 100%. Conclusions: Preparative regimens can decrease all 3 subtypes of host DCs pre-transplant. The effects of ECP on host DCs may be delayed since the decrease in DC percentages and the shift from a high, pro-inflammatory, DC1/DC2 ratio to a low, pro-tolerogenic DC1/DC2 ratio did not occur until day 0. The effects of changes in pre-transplant host DC populations on GVHD outcomes require further study.