We evaluated the occurrence of severe infections in 192 consecutive adult recipients of volunteer unrelated donor allogeneic hematopoietic stem cell transplants, with a detailed analysis of severe infections after receipt of cord blood transplants (CBTs; n = 48) or bone marrow transplants (BMTs)/peripheral blood stem cell transplants (PBSCTs; n = 144). At a 3-year median follow-up, CBT recipients had a higher risk of developing any severe infection (85% versus 69% in BMT/PBSCT recipients, P < .01). CBT recipients had a higher incidence of severe bacterial infections before day +100, but at 3 years the risks of these and other infections were similar in the CBT and BMT/PBSCT groups. In addition, the 100-day and 3-year incidences of infection-related mortality (IRM) did not differ between groups (P = .2 and .5, respectively). In multivariate analysis, the most significant risk factor for IRM in all 192 patients was monocytopenia (.2 x 10(9)/L). In CBT recipients, only neutropenia (.2 x 10(9)/L) on day +30 and low nucleated cell dose infusion (< 2 x 10(7)/kg) showed a trend for increased IRM (P = .05 in both cases). Stem cell source had no effect on day +100 or 3-year nonrelapse mortality (NRM), cytomegalovirus infection, cytomegalovirus disease (7% versus 6%), or overall survival (36% versus 39%, respectively). The number of mismatches in HLA (A, B, and DRB1) had no effect on any outcome in CBT recipients. In contrast, in the BMT/PBSCT group, the presence of any mismatch by low or high-resolution HLA typing (A, B, C, and DRB1) increased NRM and decreased overall survival (P < .01). IRM was the primary or secondary cause of death in 61% and 59% of CBT and BMT/PBSCT recipients who died, respectively. Our results confirm the relevance of severe infectious complications as source of severe morbidity and NRM after volunteer unrelated donor hematopoietic stem cell transplantation in adults, but suggest that CBT recipients have a similar risk of dying from an infection if an accurate selection of a cord blood unit is done.

Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.

Objective: To study the local and systemic behavior of the tumor necrosis factor-α (TNF-α) in patients with active uveitis. Methods: TNF-α levels were measured in aqueous humor and peripheral blood samples using an enzyme-linked immunosorbent assay from 23 patients with uveitis and 16 control patients who had been operated on for uncomplicated cataracts. Results: Aqueous humor and sera of patients with uveitis showed higher levels of TNF-α than those of controls (p < 0.001). A comparison of cytokine levels between aqueous humor and sera showed significantly higher levels of TNF-α in serum than aqueous humor (p < 0.001). Correlation studies using the regression test for successive steps showed that serum TNF-α levels correlated with recurrent uveitis (r = 0.4150; p = 0.0489). Conclusions: TNF-α is a cytokine that participates actively in the pathogenesis of clinical uveitis. Our data emphasize the greater systemic than local participation of TNF-α. Finally, an elevated serum TNF-α seems to be associated with a recurrent pattern of uveitis.

Summary. In this study, we used multiparameter flow cytometry to quantify minimal residual disease (MRD) in 165 serial bone marrow samples from 40 patients diagnosed with acute lymphoblastic leukaemia (ALL) who underwent allogeneic stem cell transplantation (allo-SCT) from siblings (n ¼ 34) or unrelated donors (n ¼ 6). Samples were prospectively taken from 24 patients before starting the conditioning regimen, at days +30, +60 and +90 and subsequently every 2-3 months. Samples from 16 patients in complete remission (CR) after allo-SCT were taken at least twice. Six of 24 patients harboured MRD (0AE2-10% of mononuclear cells) at transplant and 18 were negative. Estimated disease-free survival for the MRD+ and MRDgroups at transplant was 33AE3% and 73AE5% respectively (P ¼ 0AE03). During follow-up, increasing MRD levels were detected in nine patients, a finding that preceded marrow relapse by 1-6 months. Two patients with stable low MRD levels remained in CR. When we used flow cytometry to test the effect of donor leucocyte infusions (DLI) in six patients, we observed that the only sustained remission was achieved when DLI was applied prior to overt relapse. We conclude that MRD by flow cytometry can rapidly assess tumoral burden before transplant to predict outcome, and can be clinically useful for the timing of DLI for increasing levels of leukaemia after transplant.

Summary. Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient±donor pairs mismatched for HA-1 antigen (15´8%). Grades II±IV acute GvHD occurred in 51´6% of the HA-1-mismatched pairs compared with 37´1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0´035, OR: 2´96, 95% CI: 1´07±8´14). No differences were observed between the two groups for grades III±IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.