No abstract

Circadian activity rhythms that have been eliminated by lesions of the suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial lesions of the host allow simultaneous expression of both donor and host rhythms. Because partial SCN ablation produces characteristic changes in activity rhythms that are similar to those that occur with age, including shortened period, reduced amplitude, and fragmentation, we investigated the extent to which fetal SCN grafts may be expressed by an animal whose activity rhythm exhibits these age-dependent changes. The results indicate that expression of a transplanted clock is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and cortical tissue grafts into intact aged hosts have no effect. In those aged animals that received SCN grafts, three patterns of expression emerged in the subsequent locomotor activity record: complete dominance of locomotor rhythmicity by the donor; relative coordination between donor and host rhythms; and spontaneous switching between host and donor phenotypes. The results suggest that the expression of rhythmicity by the grafted SCN may depend on the relative amplitude or strength of signals produced by the host and donor SCN.

We conducted a prospective clinical trial to investigate the safety and efficacy of plerixafor (P) in allogeneic peripheral blood stem cells (PBSC) donors with poor mobilization response to standard-dose granulocyte colony-stimulating factor (G-CSF), defined by <2 × 10 6 CD34 + cells/kg recipient body-weight (CD34+/kg RBW) after 1st apheresis. A single dose of 240 µg/kg P was injected subcutaneously at 10 p.m. on the day of the 1st apheresis. Thirty-seven allogeneic PBSC donors underwent study treatment. The median CD34+ count in peripheral blood was 15/µl on Day 1 after G-CSF alone, versus 44/µl on Day 2 after G-CSF plus P ( p < 0.001). The median yield of CD34+ cells was 1.1 × 10 8 on Day 1 and 2.8 × 10 8 on Day 2. In contrast to a median yield of only 1.31 × 10 6 CD CD34+/kg RBW on Day 1, triggering study inclusion, a median of 3.74 × 10 6 CD CD34+/kg RBW were collected with G-CSF plus P on Day 2. Of 37 donors, 21 reached the target cell count of >4.5 × 10 6 CD34+/kg RBW (57%, 95%CI 40–73%). No donor experienced a severe adverse event requiring treatment. In conclusion, P might be considered on a case-by-case basis for healthy allogeneic donors with very poor stem cell mobilization success after G-CSF.

Central femoral lines proved to be safe and tolerable in healthy allogeneic donors but peripheral venous access should be preferred, whenever possible.

The identified risk factors allow the estimation of the efficacy of a SM in an individual donor before G-CSF administration, thus avoiding distress to both the donor and the recipient.

Background : Peripheral blood progenitor cells (PBPCs) are routinely applied worldwide for allogeneic related and unrelated stem cell transplantation. Factors influencing the mobilisation of PBPC’s in healthy donors are poorly understood. The database of the Apheresis Centre at the University of Dresden was evaluated to identify predictors of PBPC mobilisation. Methods : 4050 PBPC collections (3928 first donations, 122 second donations) of healthy unrelated donors between 1/1996 and 1/2008 were carried out according to a standardized protocol and prospectively documented in a database. Peripheral blood CD 34 counts were performed before each leukapheresis. CD 34 yield of every PBPC product was calculated in absolute numbers and per kg body weight of the recipient. All parameters are presented as median and range. Mann-Whitney test was performed for discrete variables. Correlation analysis by Pearson was applied for continuous variables. Multivariate regression analysis was carried out to detect factors independently predicting mobilization efficacy. Results : The range of peripheral CD 34+ haematopoietic stem cells obtained on day 5 was 8.7–285/μl (median 67.5/μl) in male and 6–282/μl, (median 51/μl) in female donors. The median CD 34 yield from the first leukapheresis was 5.88 ×108. Inadequate CD34-yields (&lt; 2 × 106/kg) were obtained only in 18 donors (0.45%). Peripheral CD 34 count at day 5 is significantly correlated with (positive linear regression): BMI, baseline platelet count, male sex, G-CSF application (split dose), baseline leukocyte count. Peripheral CD 34 count at day 5 correlates negatively with: female sex, single dose G-CSF application, regular alcohol consumption and regular smoking status. Linear regression analyses revealed no significant influence of donor age. Multivariate correlation analysis included sex, BMI, baseline platelets, G-CSF-application, baseline leukocytes, age and smoking. This model explained 21.2 % of the variabilityA strong correlation exists between peripheral CD 34-counts at day 5 and apheresis yield (70% of the variability explained). Conclusions : A dose of 7.5 μg/kg/d lenograstim proved to be safe and effective in a large cohort of unrelated donors for mobilizing sufficient haematopoietic progenitor cells for allogeneic transplantation. Our analysis of 4050 donations revealed significant, but very weak correlations of the peripheral CD 34-counts with donor characteristics and life style parameters. No single parameter derived from donor baseline investigation reliably predicts CD 34 yield. Further evaluation of healthy donors including comprehensive genomic linkage analysis is necessary to elucidate the variable efficiency of PBPC mobilization

No abstract

Purpose 2nd collection of Peripheral Blood Progenitor Cells (PBPC) from the same donor is increasingly required for the treatment of complications after allogeneic transplantation, but information regarding the efficacy of this procedure is still limited. Methods Within our program 212 allogeneic donors underwent a 2nd cycle of G-CSF-application and PBPC leukapheresis between 1996 and 2012. Demographical data and details of donation are shown in table 1. G-CSF (lenograstim) was administered at a median daily dose of 7.5µg/kg for 4.5d; leukapheresis was performed on day 5 and 6, if necessary. Peripheral CD 34+ counts and leukapheresis yields after both mobilization cycles were compared. The influence of age, sex, BMI, G-CSF schedule and the interval between the donations on the efficacy of the 2nd PBPC mobilization were analyzed, too. Results Median CD 34+ counts in peripheral blood were 53.2/µl at day 5 of 1st mobilization compared to 49.5/µl at day 5 of 2nd mobilization. Between 1st and 2nd donation, the median yield of CD 34+ cells/kg recipient b.w. decreased from 7.3 x 106 to 6.6 x 106 (p = 0.026, see table 2). The number of aphereses necessary in both donation episodes did not differ in the majority of donors (n=175; 82.5%). A strong correlation was observed between the amount of CD 34+ cells per recipient b.w. after the 1st and 2nd PBPC donation (r=0.89). The majority (65.4%, n=17) of donors with poor mobilization (<3 x 106 CD 34+ cells/kg recipient b.w.) after the 1st leukapheresis reached similar low CD 34+ counts after the 2nd mobilization. The interval between both mobilization cycles did not affect the results of the 2nd donation. According to an adjusted model, the other variables (age, sex, BMI and G-CSF-schedule) had no additional influence on mobilization efficacy in the 2nd cycle of G-CSF application. Conclusions In the largest group of healthy donors reported so far, we could demonstrate a slight reduction (about 10%) of PBPC yield after the 2nd mobilization that might not be clinically significant. Demographic variables affected the results of both mobilization episodes in the same way and the interval between them was of no significance. Our data support the assumption, that stem cell mobilization is probably determined by genetic factors and the outcome of a 2nd donation can easily be predicted by the results of the 1st one. Disclosures: No relevant conflicts of interest to declare.