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Infusions of ex vivo-expanded (EXE) mobilized blood cells have been explored to enhance haematopoietic recovery following high dose chemotherapy (HDT). However, prior studies have not consistently demonstrated improvements in trilineage haematopoietic recovery. Three cohorts of three patients with breast cancer received three cycles of repetitive HDT supported by either unmanipulated (UM) and/or EXE cells. Efficacy was assessed by an internal comparison of each patient's consecutive HDT cycles, and to 106 historical UM infusions. Twenty-one cycles were supported by EXE cells and six by UM cells alone. Infusions of EXE cells resulted in fewer days with an absolute neutrophil count (ANC) <0·1 × 109/l (median 2 vs. 4 d, P = 0·002) and 3 d faster ANC recovery to >0·1 × 109/l (median 5 vs. 8 d, P = 0·0002). This resulted in a major reduction in the incidence of febrile neutropenia compared with UM cycles (0% vs. 83%; P = 0·008) and in 66% of historical UM cycles ( P = 0·01) and a marked reduction in hospital re-admission. There were also fewer platelet transfusions required (43% vs. 100%; P = 0·009). We conclude that EXE cells enhance both neutrophil and platelet recovery and reduce febrile neutropenia, platelet transfusion and hospital re-admission. [ABSTRACT FROM AUTHOR]

ICI 182,780, a potent, new steroidal antiestrogen without apparent agonist activity, appears to be a potent modulator of the classic multidrug resistance (MDR) phenotype in the CEM/A7, CEM/VLB100 and K562/VIN100 MDR cell lines. This reagent had no effect on the respective parental CCRF-CEM and K562 cell lines. The use of 1.25 microM ICI 182,780 resulted in a 6- to 7-fold decrease in doxorubicin resistance in the CEM/A7 and CEM/VLB100 cell lines. A dose-response effect was observed at ICI 182,780 concentrations of up to 5 microM. As compared with tamoxifen (TAM), ICI 182,780 was 2 and 4 times more effective in the K562/VIN100 and CEM/A7 cell lines, respectively. ICI 182,780 at 0.625 microM increased [3H]-daunomycin uptake (P < 0.0001) as effectively as 5 microM TAM in the resistant CEM/A7 line. Drug-efflux studies showed that 5 microM ICI 182,780 significantly decreased drug efflux as compared with 5 microM TAM (P < 0.0001). Estradiol (EST) at 10 microM increased doxorubicin resistance by 1.2-1.3 times in the CEM/A7 and CEM/VLB100 cell lines and significantly decreased drug accumulation (P = 0.002) and retention (P < 0.001) in the CEM/A7 cell line. However, the addition of 10 microM EST to 1-2 microM ICI 182,780 did not inhibit the ability of ICI 182,780 to modulate doxorubicin resistance in the two resistant cell lines. Using reverse-phase high-performance liquid chromatography (HPLC) to measure lipophilicity, we found no apparent association between the ability of ICI 182,780, TAM or EST to modulate resistance and their relative hydrophobicity. [ABSTRACT FROM AUTHOR]

A response from the author of the article regarding the self-regulation of autologous cell therapies is presented.

The authors discuss issues when it comes self-regulating autologous cell therapies in Australia. They highlight the increasing number of clinicians in the country who adopted autologous cell therapies to treat several disorders such as rheumatological conditions. The also highlight the Therapeutic Goods Administration's prospective authorisation of autologous cell therapies.