Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor.

Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are well-documented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure-'dual CB/TPD-MHSC transplant'-that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor.

This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16-60 years) and weight 70 kg (43-95 kg), received CBTs (median 2.39 x 10(7) total nucleated cell (TNC) per kg and 0.11 x 10(6) CD34+ per kg) and TPD-MHSC (median 2.4 x 10(6) CD34+ per kg and 3.2 x 10(3) CD3+ per kg). Median time to ANC and to CB-ANC >0.5 x 10(9)/l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets >20 x 10(9)/l was 32 days (MCI 0.78). MCI for grades I-IV and III-IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI=0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan-Meier) were 56 % and 47% (63% and 54% for patients

Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands.

The purpose of this study was to examine whether several allelic variants in the polymorphic interleukin (IL)-10 promoter region were related with an increased risk of developing systemic lupus erythematosus (SLE) in Spanish patients from Canary Islands. Microsatellites (MS) at positions -4000 and -1200 (IL10R and IL10G, respectively) and single nucleotide polymorphisms (SNPs) (MS) at positions -1082G/A, -819C/T and -592C/A of the IL-10 promoter were analysed in patients with SLE and healthy controls from Canary Islands (Spain). We found that SNPs but not MS were associated with SLE. The GCC haplotype frequency was significantly higher in SLE patients (0.43) than in healthy donors (0.33) [P = 0.02; OR = 1.50 (95% CI = 1.06-2.14)], whereas the ACC haplotype was less represented in patients (0.28 vs. 0.37) [P = 0.02; OR = 0.64 (95% CI = 0.44-0.92)]. To assess the functional role of genotypes, serum IL-10 levels from patients and controls were quantified by ELISA. Also, the lipopolysaccharide-induced IL-10 secretion by monocytes from healthy controls was evaluated in vitro. Serum IL-10 levels were higher in patients [median (interquartile range) = 2.8 pg/mL (1.8-4.2)] than in controls [0.9 pg/mL (0-3.5)] (P = 0.02), but no association was observed between serum IL-10 levels or lipopolysaccharide-induced IL-10 secretion and the IL-10 promoter haplotypes. These data suggest that the IL-10 promoter haplotype that produces higher levels of cytokine is associated with SLE in patients from Canary Islands.