High dose rabbit antithymocyte globulin induction in living related liver transplantation.

BACKGROUND/AIMS: Induction with rabbit antithymocyte globulin (RATG) has been reported to be effective in cadaveric liver transplantation. The aim of this study was to compare two immunosuppressive protocols in adult living-related liver transplantation (LRLT). METHODOLOGY: From May 2001 through May 2003, 34 LRLT were performed. The first 17 patients (group 1) were treated with tacrolimus (TAC) and steroids. The next 17 patients (group 2) were treated with a steroid-sparing protocol using RATG. RESULTS: The one-year patient and graft survival was respectively 76.5% and 64.7% for group 1 and 88.2 and 76.5% for group 2 (p = 0.037 and p = NS, respectively). Incidence of acute cellular rejection was 41.2% in group 1 compared to 47% in group 2 (p = NS). Mean daily TAC dose at 6 months was 6.5 +/- 1.1 mg/day in group 1 and 3.2 +/- 0.9 mg/day in group 2 (p < 0.001). In group 1, 41.1% experienced CMV infection compared to 11.7% in group 2 (p = NS). CONCLUSIONS: These results suggest that this approach of RATG induction followed by postoperative, steroid-free, and low-dose TAC is safe and provides for adequate immunosuppression and similar outcome when compared to controls treated with standard TAC and steroid immunosuppression.

Need for kidney transplantation in HIV-positive individuals: results of a survey in Italy.

It is well known that HIV+individuals can be affected by end-stage renal diseases (ESRD). Despite the availability of new effective antiretroviral therapies, HIV-infected people are generally excluded from kidney transplantation, the treatment of choice for ESRD. A small number of transplantations have been performed, with encouraging data in terms of graft and patient survival. To evaluate the need of kidney transplant for HIV+individuals, we designed a multicentre study which enabled the simulation of a virtual transplant waiting list for those on dialytic treatment. In 38 participating infectious disease units, 16 HIV+patients were selected for renal replacement treatment/dialytic treatment, and they were enrolled. Clinical data were collected in order to apply general exclusion criteria and evaluate HIV clinical status. Clinical data confirmed inclusion of 7/16 patients. After application of CD4+count and HIV viraemia for further selection, the number of subjects was significantly reduced. Six patients had CD4+count greater than 200/cmm (2/6 with undetectable HIV viraemia). Only 3 patients had CD4+higher than 350/cmm (1/3 with undetectable HIV viraemia). Our data represent the first evaluation of the need and eligibility for kidney transplantation for HIV+subjects with ESRD. Application of HIV infection related parameters as selection criteria has a great strength in reducing the waiting list of HIV+subjects suitable for kidney transplant and could be carefully considered when planning inclusion/exclusion criteria for experimental purposes.

Acute graft-versus-host disease and steroid treatment impair CD11c+ and CD123+ dendritic cell reconstitution after allogeneic peripheral blood stem cell transplantation.

Human dendritic cells (DC) comprise 2 subsets-plasmacytoid CD123(+) and myeloid CD11c(+) DC-that may have distinct roles in the regulation of immunity after allogeneic hematopoietic stem cell transplantation. In this study, we analyzed the kinetics of CD123(+) DC and CD11c(+) DC reconstitution in 31 patients who underwent transplantation with allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells from HLA-identical sibling donors after myeloablative conditioning. Lineage marker-negative HLA-DR(+) CD11c(+) CD11c(+) DC and lineage marker-negative HLA-DR(+) CD123(+) CD123(+) DC, as well as monocytes and lymphoid subsets, were enumerated in donor grafts and in the PB of patients at various time points after transplantation. Reconstitution of both CD11c(+) DC and CD123(+) DC to normal levels occurred within 6 to 12 months and was not affected by the diagnosis, preparatory regimen, or graft composition. However, PB CD11c(+) DC and CD123(+) DC counts were significantly reduced in patients with acute GVHD grade II to IV (at 1 and 3 months) and grade I (at 1 month). Patients with chronic GVHD instead showed reduced CD123(+) DC counts only 6 months after transplantation. Moreover, treatment with steroids (>0.1 mg/kg) was significantly associated with reduced PB CD11c(+) DC and CD123(+) DC counts at all time points after transplantation. In multivariate analysis, only acute GVHD affected DC reconstitution early after transplantation. These results will prompt new studies addressing whether DC reconstitution correlates with immunity against infectious agents or with graft-versus-tumor reactions after PB stem cell allotransplantation.