Doubling time of soluble CD23: a powerful prognostic factor for newly diagnosed and untreated stage A chronic lymphocytic leukemia patients.

Soluble CD23 (sCD23) levels correlate with the stage, prognosis and overall survival (OS) of patients with chronic lymphocytic leukemia (CLL). Therefore, we prospectively evaluated sCD23 doubling time (sCD23DT) as a prognostic factor for time to treatment (TTT) and OS in 56 newly diagnosed and untreated CLL patients at Binet stage A, and compared it to the most commonly used biological prognostic factors: lymphocyte doubling time, immunoglobulin variable heavy chain (IgVH) mutational status and zeta-associated protein-70 (ZAP-70), CD38, and lipoprotein lipase (LPL) expression. In patients with sCD23DT <1 year, the median TTT and OS were 20 and 83 months compared to 141 and 177 months in patients with sCD23DT >1 year (P<0.0001). Among patients with poor prognostic factors (ZAP-70+, LPL+ and CD38+), an sCD23DT <1 year identified a subpopulation with a shorter TTT. Patients with unmutated IgVH and an sCD23DT <1 year had a median TTT and OS of 14 and 83 months, respectively, whereas these values were 70 and >177 months when sCD23DT was >1 year (P<0.0001 and P=0.0219, respectively). Finally, in a Cox multivariate analysis, sCD23DT was the sole independent prognostic factor for TTT (P=0.0027). Furthermore, sCD23DT refines the prognosis given by other classical prognostic factors. These observations support the introduction of sCD23 evaluation into the routine assessment of CLL patients.

[Cord blood: from bench to bedside]. / Le sang de cordon: du laboratoire au lit du malade.

Since 1974, umbilical cord blood (CB) has been shown to contain haematopoietic stem cells similar to stem cells from the bone marrow. In 1988, E. Gluckman and her colleagues performed - successfully - the first familial CB transplantation and cured a 5 years old child suffering from Fanconi's anemia. Rapidly, CB banks were organised throughout in the world and thanks to this novel source of haematopoietic stem cells, we can now find a donor for 75 % of the patients requiring a "bone marrow" transplantation. The major benefit of CB as a source of hematopoietic stem cells is its easy access. CB also allows a more significant degree of HLA incompatibility and thus offers an opportunity of transplantation to ethnic minorities for whom no HLA identical donors are available. However, several studies have shown that the number of cells harvested in a CB was closely correlated with the engraftment post transplantation and today, a minimum of 3.7 x 10(7) mononucleated cells/kg is recommended. This required amount of cells is not always reached due to the small volume often harvested from a CB. Therefore, to apply CB transplantations to adults, different approaches are currently being investigated : coinfusion of haploidentical cells, mesenchymal cells, a second CB, or the addition of CB expanded ex-vivo. Among these approaches, double CB transplantation seems nowadays the most promising alternative and ongoing studies should soon inform us whether the duration of aplasia will be improved.

Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection: phenotype, proliferation kinetics and differentiation potential.

BACKGROUND: BM mesenchymal stem cells (MSC) have the capacity for renewal and the potential to differentiate into multiple tissues. In this study, we compared different enrichment methods to obtain MSC from BM. METHODS: Three different methods were compared with a view to obtaining MSC more rapidly from BM: negative selection (RosetteSep and MACS) and plastic adhesion. The three cell fractions were grown in complete alpha-minimum essential medium in order to evaluate their proliferative capacity, their phenotype during culture and their potential to differentiate into adipocytes, osteocytes and chondrocytes. Identification of MSC was performed by immunofluorescence with putative mesenchymal markers SH2 and SH3 but also with hematopoietic markers. RESULTS: After negative selection, only 1+/-0.2% and 2.9+/-0.8% of cells were recovered from BM with the RosetteSep and MACS methods, respectively. However, negative depletion permitted a homogeneous population of MSC, with more than 90% SH2+ and SH3+ cells, to be obtained rapidly and in large quantities after 10 days of culture. Similar homogeneity was observed after three passages if the plastic adhesion was used as selection method and after an average of 25-30 days of culture. Different levels of MSC maturity were also suggested by the variable level expression of Stro-1. DISCUSSION: Depleting selection by RosetteSep may represent an easy method of obtaining MSC rapidly from BM with the aim of potential therapeutic use.