Resveratrol 1 (3,4',5-trihydroxy-trans-stilbene), a phytoalexin present in grapes and other food products, has recently been suggested as a potential cancer chemopreventive agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. This triphenolic stilbene has also displayed in vitro growth inhibition in a number of human cancer cell lines. In this context, a series of cis- and trans-stilbene-based resveratrols were prepared with the aim of discovering new lead compounds with clinical potential. All the synthesized compounds were tested in vitro for cell growth inhibition and the ability to induce apoptosis in HL60 promyelocytic leukemia cells. The tested trans-stilbene derivatives were less potent than their corresponding cis isomers, except for trans-resveratrol, whose cis isomer was less active. The best results were obtained with compounds 11b and 7b, the cis-3,5-dimethoxy derivatives of rhapontigenin 10a (3,5,3'-trihydroxy-4'methoxy-trans-stilbene) and its 3'-amino derivative 10b, respectively, which showed apoptotic activity at nanomolar concentrations. The corresponding trans isomers 12b and 8b were less active both as antiproliferative and as apoptosis-inducing agents. Of interest, 11b and 7b were active toward resistant HL60R cells and their activity was higher than that of several classic chemotherapeutic agents. The flow cytometry assay showed that at 50 nM compounds 7b or 11b were able to recruit almost all cells in the apoptotic sub-G(0)-G(1) peek, thus suggesting that the main mechanism of cytotoxicity of these compounds could be the activation of apoptosis. These data indicate unambiguously that structural alteration of the stilbene motif of resveratrol can be extremely effective in producing potent apoptosis-inducing agents.

Autologous transplantation is a treatment option for relapsed childhood acute lymphoblastic leukemia (ALL) in second complete remission (CR2) when a suitable donor is not available. In an attempt to prevent relapses originating from graft leukemic contamination, the experimental protocol of in vitro purification of leukapheretic products with monoclonal antibodies (MoAbs), previously reported for adults, was adopted in 11 of 12 consecutive patients (median age, 9 years) with B cell precursor ALL in CR2 after late relapse (median, 37; range, 31-51 months after the onset) enrolled between July 1997 and July 1999 at a single pediatric center. At a median of 12 days after the mobilizing chemotherapy followed by G-CSF, a median of 13.9 (range, 5.9-18.7) × 10 6 CD34 + cells/kg were collected from each patient and a median of 7.5 (range, 4.1-12.6) × 10 6 CD34 + cells/kg underwent the purification procedure. The first step of immunorosetting allowed a one-log reduction of the total cell count, by eliminating more than 90% of the CD11b

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In recent years peripheral blood stem cell (PBSC) collection for allogeneic or autologous transplantation has experienced an increased use in the onco-hematological setting. The latest generation cell separators allow a satisfactory and safe PBSC collection. Nevertheless, as in all therapeutic apheresis procedures, patients may experience procedure-related side-effects, mainly vasovagal reactions or symptoms related to hypocalcemia and/or hypomagnesemia. We investigated electrolyte changes in 18 patients, with a median age of 46 years (range 7-62), undergoing PBSC collection from January to April 1998. A significant decrease in total calcium in the final sample (9.65 ± 0.7 mg/dL) with respect to the basal one (9.2 ± 0.6 mg/dL, P < 0.05) was observed; also ionized calcium decreased markedly from the first sample drawn at +30 minutes: 1.22 ± 0.14 vs. 1.03 ± 0.15 mmol/L (P < 0.05), and a highly significant difference emerged when basal value were compared to the final value: 1.22 ± 0.14 vs. 0.94 ± 0.13 mmol/L (P < 0.0001). Similar findings affected potassium concentration: 4.1 ± 0.4 vs. 3.3 ± 0.3 mEq/L (P < 0.0001). Three out of eighteen patients (16.7%) reached a final potassium level <3.0 mEq/L, and eight out of eighteen (44.5%) showed a potassium concentration decrease >20% with respect to the basal value. A mild metabolic alkalosis occurred during the procedure: pH increased from 7.35 ± 0.02 to 7.43 ± 0.028 (P < 0.001), and plasma bicarbonate concentration increased from 27.48 ± 2.21 to 32.44 ± 2.52 mmol/L (P < 0.01). Sodium and chloride did not differ in the final sample with respect to the basal sample. None of our patients experienced clinically relevant side effects related to severe electrolyte changes (i.e., >20% with respect to the basal value). Because our current therapeutic schedules include patients older than 50 years in the PBSC collection and transplantation program and since it is well known that subclinical myocardial disease may occur in up to 4% of middle-aged males, we suggest that patients aged 50 or older undergoing PBSC collection procedures be carefully monitored in order to identify significant electrolyte variation, especially if they present with low serum potassium levels. However, further investigation of larger patient series are needed to determine the clinical relevance of serum potassium changes during apheresis.