Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning.

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days -16 and -15, fludarabine 30 mg/m(2) per day on day -7 through -3, IV busulfan 130 mg/m(2) per day on days -4 and -3 and cyclophosphamide 1500 mg/m(2) on day -2. rATG levels were therapeutic in all patients on day -14, but were sub-therapeutic (<1 µg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.

Risk profiles in type 2 diabetes (metabolic syndrome): integration of IL-10 polymorphisms and laboratory parameters to identify vascular damages related complications.

Recently it has been reported that low serum IL-10 levels are associated with an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus (T2DM). We investigated whether the -1087G/A (rs1800896), -824C/T (rs1800871), -597C/A (rs1800872) IL-10 polymorphisms were associated with type 2 diabetes in a study on a cohort of Italian Caucasians comprising 490 type 2 diabetic and 349 control subjects. Stratifying the data according to IL-10 genotypes, trends for the progressive increase of glucose and neutrophil levels were observed in -1087GG vs. -1087GA vs. -1087AA positive diabetic patients (-1087GG<-1087GA<-1087AA). In addition, evaluating the laboratory parameters according to the -597/-824/-1087 derived haplotypes a significant increase of neutrophils was found in diabetic vs. non-diabetic -597A/ -824T/-1087A positive subjects (Student t test = 3.707, p<0.01). In an attempt to integrate clinical laboratory and immunogenetic data to determine whether these factors taken together define sufficient risk sets for type 2 diabetes we performed the grade-of-membership analysis (GoM). GoM allowed to identify a population of subjects negative for IL-10 -824T allele, 74.4% of which were diabetic patients characterised by vascular damages (Chronic kidney failure and/or Myocardial Infarction), reduction of haematocrit, increase of blood urea nitrogen, creatinin and monocyte levels. These data seem to suggest that -597A/-824T/-1087A negative subjects are more prone to the major type 2 diabetic vascular damages and allow to hypothesise that the contemporary evaluation of some simple hematochemical parameters and IL-10 SNPs may allow identifying diabetic patients with the worse prognostic profile, needing both better complication prevention planning and therapeutic strategies.