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The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLAidentical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade ll-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1- 61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2- 16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo- HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo- HSCT proposed to younger patients. This study was registered at clinicaltrials. [ABSTRACT FROM AUTHOR]

The temporal association of tonsillitis and hematuria or proteinuria in IgA nephropathy suggests that there might be a link between the physiological properties of the secondary lymphoid organ that tonsils represent and the mesangial deposition of IgA characteristic of this nephropathy. A number of clinical and ex-vivo data support this hypothesis. One of the earliest was the demonstration of the dimeric nature of mesangial IgA, composed of IgA monomers linked by a J chain, yet lacking the polyIg receptor acquired by secretory IgA during transcytosis through epithelial cells. This molecular structure is that of IgA synthesized in human tonsils, the epithelium of which lacks polyIg receptor. Moreover, tonsils from patients with IgA nephropathy display an abnormal partition of IgG and IgA producing plasma cells associated with a significantly developed web of high endothelial venules. IgA nephropathy could thus be in part related to an alteration of IgA precursors homing in tonsils. Tonsillectomy thus would present the advantage of removing an abnormally functioning source of dimeric IgA. Performed early enough in the course of the renal disease, tonsillectomy could suffice to halt the development of the nephropathy and restore the kidneys to health. [ABSTRACT FROM AUTHOR]

Background: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU.Methods: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center.Results: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death.Conclusions: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration.Trial Registry: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex andmonosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ KMT2A-AFF1 and 14q32/IGH translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCTtime.Aworse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex andmonosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years. [ABSTRACT FROM AUTHOR]

The intercellular adhesion molecule-I (ICAM-l) is a membrane-bound molecule involved in cell-cell adhesive interactions which is upregulated on inflammatory epithelial cells. The levels of soluble ICAM-l (sICAM-1) shed into the gingival crevicular fluid (GCF) were studied in healthy patients and patients with gingivitis, adult periodontitis or rapidly progressive periodontitis. using an ELISA technique. Clinical parameters including plaque index. gingival index, probing depth. and bleeding on probing were recorded following careful sampling of GCF with standardised filter strips. In GCF, sICAM-l levels were higher for patients with plaque (p = 0.04) and for patients with inflammation (p = 0.02), but did not correlate with disease classifications. These results suggest that elevated GCF sICAM-l levels may represent increased shedding of this molecule in the interstitial fluid as a result of membrane-hound ICAM-l upregulation on ICAM-1 gingival-bearing cells in relation with plaque accumulation and inflammation. [ABSTRACT FROM AUTHOR]