The graft-versus-leukemia effect is mainly restricted to NIH-defined chronic graft-versus-host disease after reduced intensity conditioning before allogeneic stem cell transplantation.

Incidence on relapse and nonrelapse mortality (NRM) of chronic graft-versus-host disease (GVHD), per National Institutes of Health (NIH) criteria, is not well defined after reduced-intensity conditioning (RIC) regimens. We analyzed the association of chronic GVHD with the risk of relapse and NRM using Cox models in 177 consecutive patients who underwent transplantation for hematological malignancies after RIC. The cumulative incidence of chronic GVHD at 36 months was 74% when using Seattle's criteria compared with 54% with NIH consensus. In Cox model, NRM was significantly higher in patients with late-onset, persistent and recurrent acute GVHD (hazard ratio (HR): 6, 25 and 11; P = 0.014, P<0.0001, P<0.0001, respectively). The cumulative incidence of relapse was significantly decreased in patients with chronic GVHD compared with no GVHD group using either Seattle's or NIH criteria (HR 0.43 and 0.38; P = 0.022 and 0.016, respectively), whereas the presence of late-onset, persistent and recurrent acute GVHD was not associated with a decreased rate of relapse (HR: not significant, 0.70 and 0.71; P = not significant, P = 0.73 and P = 0.54, respectively). Chronic GVHD per NIH consensus definition is associated with the graft-versus-tumor effect, whereas all forms associated with acute features beyond day 100 are associated with NRM.

Effect of the anti-factor Xa and anti-factor IIa activities of low-molecular-weight heparins upon the phases of thrombin generation.

BACKGROUND: Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) by different depolymerization procedures, vary in both their relative abilities to enhance the inhibition of FXa (anti-FXa) and thrombin (anti-FIIa), and in their physicochemical properties. OBJECTIVE: We aimed to profile the inhibition of thrombin generation induced by bemiparin, enoxaparin, nadroparin, dalteparin and tinzaparin in platelet-rich plasma (PRP), and to compare them with UFH and fondaparinux (a synthetic pentasaccharide that specifically enhances FXa inhibition). METHODS: Different LMWHs, UFH or fondaparinux were added to normal PRP. Thereafter, tissue factor-triggered thrombin generation was assessed using the Thrombogram-Thrombinoscope assay. RESULTS: At equivalent anti-FIIa activity concentrations, LMWHs and UFH exhibited similar inhibitory effects upon thrombin generation. However, when used at equivalent anti-FXa activity concentrations, tinzaparin was significantly more active than the other LMWHs at inhibiting thrombin generation, and had similar activity to that of UFH. Enoxaparin, nadroparin and dalteparin all showed similar inhibitory activities. In these experiments, bemiparin exhibited the lowest inhibitory effect on thrombin generation of all the LMWHs. At 0.1 microg mL(-1) (0.093 anti-FXa IU mL(-1)), fondaparinux inhibited the rate of thrombin generation by 50%. A 7-fold higher concentration of fondaparinux was required to inhibit the endogenous thrombin potential by 50%. CONCLUSIONS: LMWHs have a variable inhibitory effect on thrombin generation in vitro when compared by anti-FXa activity, but are similar when compared by their anti-FIIa activities. The rate of thrombin generation during the propagation phase, rather than the endogenous thrombin potential, is more sensitive to the anticoagulant activity of fondaparinux and the polysaccharide chains of LMWHs possessing only anti-FXa activity.