RESUMO
INTRODUCTION: COBE SPECTRA [COBE] (Terumo, BCT Lakewood CO) apheresis system has been the most used device for hematopoietic progenitor cells (HPC) collection. Recently, it has been replaced by the SPECTRA OPTIA [OPTIA] (Terumo, BCT Lakewood CO) apheresis system. The aim of our study is to compare both methods for HPC collection. MATERIAL AND METHODS: We retrospectively compared 302 HPC collection apheresis procedures (115 allogeneic donors and 187 autologous). The study cohort was divided according to the apheresis system used to analyze the differences between COBE and OPTIA, specifically efficacy of apheresis procedure and product characteristics. RESULTS: OPTIA collections result in a higher CD34+ collection efficiency in both groups (autologous 45.3% vs 41%, P < .006; allogeneic 54.9% vs 45%, P < .0001). The total of CD34+ cells ×106 /kg recipient collected in the product were comparable in both groups (autologous 2.9 in OPTIA group vs 2.8 in COBE group, P = .344; allogeneic 6.2 in OPTIA group vs 5.8 in COBE group, P = .186). The percentage of platelet loss in autologous donors was significantly lower (35.7% vs 40.8%, P < .01). Regarding quality of the product, we observed a significantly lower hematocrit in products collected with OPTIA in both groups (1.8% vs 4%, P < .0001) as well as significantly lower amount of leukocytes (median 153.4 vs 237.2 × 109 /L in autologous, P < .0001; 239.5 vs 340.2 × 109 /L in allogeneic P < .0001). CONCLUSION: Both apheresis systems are comparable in collection of hematopoietic progenitor cells, with significantly higher collection efficiency with the OPTIA system. Collection products obtained with OPTIA contain significantly lower hematocrit and leukocytes.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Transplante HomólogoRESUMO
Aldehyde dehydrogenases (ALDHs) are enzymes catalyzing the NAD(P)+-dependent oxidation of aldehydes to their corresponding carboxylic acids. High ALDH activity has been related to some important features of cancer stem cells. ALDH1A enzymes, involved in the retinoic acid signaling pathway, are promising drug targets for cancer therapy, and the design of selective ALDH1A inhibitors has a growing pharmacological interest. In the present work, two already known compounds (DEAB and WIN 18,446) and novel thiazolidinedione and pyrimido quinoline acetic acid derivatives (compounds 5a and 64, formerly described as aldo-keto reductase inhibitors) were tested as inhibitors of the ALDH1A enzymes (namely, ALDH1A1, ALDH1A2 and ALDH1A3) as a first step to develop some potential drugs for cancer therapy. The inhibitory capacity of these compounds against the ALDH1A activity was characterized in vitro by using purified recombinant proteins. The IC50 values of each compound were determined indicating that the most potent inhibitors against ALDH1A1, ALDH1A2 and ALDH1A3 were DEAB, WIN 18,446 and compound 64, respectively. Type of inhibition and Ki values were determined for DEAB against ALDH1A1 (competitive, Kiâ¯=â¯0.13⯵M) and compound 64 against ALDH1A3 (non-competitive, Kiâ¯=â¯1.77⯵M). The effect of these inhibitors on A549 human lung cancer cell viability was assessed, being compound 64 the only inhibitor showing an important reduction of cell survival. We also tested the effect of the ALDH substrate, retinaldehyde, which was cytotoxic above 10⯵M. This toxicity was enhanced in the presence of DEAB. Both DEAB and compound 64 were able to inhibit the ALDH1A activity in A549â¯cells. The current work suggests that, by blocking ALDH activity, drug inactivation may be avoided. Thus these results may be relevant to design novel combination therapies to fight cancer cell chemoresistance, using both enzyme inhibitors and chemotherapeutic agents.