Long-Term Course of Haemoglobin and Ferritin Values in High-Frequency Donors of Whole Blood and Double Erythrocyte Apheresis.

BACKGROUND: High-intensity donation is a risk factor for iron deficiency in blood donors. Interdonation intervals for whole blood (WB) donation and double unit red blood cell apheresis (2RBC) vary among countries. We retrospectively evaluated the course of haemoglobin (Hb) and ferritin values in men regularly donating WB 4 times a year or 2RBC twice a year (i.e., maximal frequency) over a period of 48 months. METHODS: Data of male donors with 16 WB or 8 2RBC consecutive donations were analysed. The minimum Hb levels for WB donation and 2RBC apheresis (collection of 360 mL RBC) were 135 and 140 g/L, respectively. There was no lower limit set for ferritin, and no iron was substituted. RESULTS: We identified 294 WB (mean age 53 years, SD 11) and 151 2RBC donors (mean age 48 years, SD 9) who donated at a mean interval of 97 (SD 18) and 201 days (SD 32), respectively, between January 1, 2008, and December 31, 2013. At baseline, Hb and ferritin values were lower in WB donors compared to 2RBC donors, with a mean Hb of 153 g/L (SD 13) versus 159 g/L (SD 8) and a mean ferritin of 44 µg/L (SD 52) versus 73 µg/L (SD 56; p < 0.001 for both parameters), respectively. Ferritin was below 15 µg/L in 40 WB (14%) and in 4 (3%) 2RBC donors. In WB donors, the mean Hb levels at baseline versus last donation showed no significant difference (153 vs. 152 g/L, p = 0.068), whereas the mean ferritin levels decreased significantly (44 vs. 35 µg/L, p < 0.001). The 2RBC donor group displayed a statistically different decrease in both the mean Hb levels (158 vs. 157 g/L; p < 0.05) and the mean ferritin levels (73 vs. 66 µg/L; p = 0.052). The lowest Hb was measured at the 11th WB donation (152 g/L; p < 0.05) and at the 4th 2RBC apheresis (157 g/L; p < 0.05). There was no deferral due to low Hb at any time. The lowest ferritin was shown at the 4th WB (37 µg/L) and at the 3rd 2RBC donation (60 µg/L), respectively. At the last visit, ferritin was below 15 µg/L in 23 WB donors (8%) and in 2 2RBC donors (1%). CONCLUSIONS: High-intensity male donors with an interdonation interval of 12 weeks for WB donation and 24 weeks for 2RBC apheresis maintain acceptable Hb levels and, after an initial decline, stable ferritin levels despite ongoing blood donation.

Adverse events and retention of donors of double red cell units by apheresis.

BACKGROUND: Safety of double-erythrocyte (2RBC) collection and reasons for ceasing 2RBC donation were retrospectively analysed in the blood donor population of Basel, Switzerland. METHODS: Donors with at least 1 2RBC apheresis were included in the study. Minimal requirements were Hb ≥140 g/L and body weight ≥70 kg; serum ferritin (SF) values were measured routinely, but were not part of the selection criteria. 2RBC collections were performed with ALYX devices at 6-month intervals. Adverse events (AEs) were systematically recorded and classified according to the ISBT EHN 2008 criteria. Data of procedures were retrieved from the ALYX software. Demographics, apheresis data and AEs were analysed with descriptive statistics. RESULTS: Data of 4,377 2RBC aphereses performed in 793 donors (779 males) between 1(st) January 2003 and 31(st) May 2015 were evaluated. Mean donor age at first 2RBC donation was 44 years (standard deviation [SD] 21), median number of donations was 4 (interquartile range [IQR] 8); 32% of the donors underwent a single procedure. There were 161 AEs, mostly local haematomas (55%) and vasovagal reactions (20%); fatigue was reported in 6% of the cases and was more frequent than citrate toxicity. Two severe AEs were observed. The most frequent reasons for abandoning 2RBC donation were low SF levels and donor choice (both 11%), but most donors simply did not reply to invitations (16%). Overall, procedure-related causes (AEs, low SF levels, no time for apheresis, inadequate venous access) were observed in 14% of the cases. At the end of the observation period, 40% of the donors were still active blood donors, but only 20% were donating 2RBC. DISCUSSION: 2RBC donation is overall safe. Donor retention was low over a period of 11 years. An important reason for abandoning 2RBC was the detection of low SF levels. The impact of fatigue on donor retention and the course of iron stores after repeated 6-monthly 2RBC apheresis require further investigation.

Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like cells enriched with tumor spheroids from a non-small cell lung cancer cell line.

Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell (CSC) populations. In this study, we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. However, the CSC-like cells exhibited resistance to gemcitabine-induced apoptosis. Collectively, the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.