Over a Third Of Donors Who Are Smaller Than Their Recipient Fail To Meet The CD34+ Cell Dose Requested For PBSC Transplantation
Authors: Billen Annelies , Madrigal J. Alejandro , Shaw Bronwen E. 
Published: October 2019

Background
It is of clinical relevance to recognize donors who are unlikely to meet the requested stem cell dose for transplantation, as this group may benefit from an alternative mobilization regimen. This study was performed to evaluate the frequency of unrelated donor peripheral blood stem cells (PBSC) collections that met the requested dose and the impact of donor factors on this.

Methods
All sequential PBSC collections facilitated by the national registry (n = 325) from January through December 2011 were analyzed. All donors were mobilized with lenograstim at 10 μg/kg/day subcutaneously ± 10%. G-CSF was administered for four consecutive days. If the CD34 target cell yield was not achieved after one day of apheresis, a further dose of G-CSF was given and a second collection performed (to a maximum of two aphereses). Apheresis was carried out in 1 of 4 collection centers using the COBE Spectra device. The standard collection time was 4 hours. Donor factors analyzed included age, gender, weight and presence of a central line.

Results
Donor characteristics are shown in table 1. The median cell dose requested was 4 x 106 CD34+cells/kg recipient weight (range 3-10). The median CD34 dose collected was 6.0 x 106/kg (range 0.44-156.7). 71% of requests were met after 1 day and 85% of requests were met after 2 days of collection.
In univariate analysis, we found that donor weight (t-test, p< 0.001) and female gender (OR= 5.5; 95% CI 3, 9.8; chi square, p< 0.001) were significantly associated with not reaching the target yield. Any negative difference in weight between donor and recipient resulted in a higher chance of not meeting the requested dose (chi square, p< 0.005). Even a negative weight difference of 5 kg resulted in an odds ratio of not meeting the requested dose of 2.5 (95% CI 1.5, 4.1) after 1 day of collection and an odds ratio of 2 (95% CI 1.1, 3.8) after 2 days of collection. Age and having a central line in situ were not significantly associated with reaching the requested cell dose. All the above findings were valid both after 1 day and 2 days of collection.
After stepwise binary logistic regression, gender (p < 0.001) and difference between donor and recipient weight (p = 0.001) remained significantly associated with target dose being met after 1 day of collection. There was a trend towards significance after 2 days of collection (p = 0.09). Interestingly, donor weight lost significance after adjusting for gender (p = 0.21).
Poor mobilizers were defined as a mobilization of less than 2 x 106 CD34 cells per recipient weight. Female gender (OR = 5.7; 95% CI 2.1, 12.2; chi square, p < 0.001), donor weight (t-test, p< 0.001) and difference between donor and recipient weight (t-test, p < 0.001) were associated with poor mobilization. A donor that was more than 5 kg lighter than its recipient was significantly more at risk of being a poor mobilizer (OR: 5.7; 95% CI 2.2, 15; chi square, p < 0.001). Only the difference between donor and recipient weight remained significant after multivariate analysis (p < 0.05).

Conclusions
This study shows than women and donors who are lighter than their recipient have a decreased likelihood of meeting the transplant physician's requested dose. Donors who are more than 5 kg lighter than their recipient are especially at risk. New strategies to improve mobilization in such donors are needed. Previous studies have shown that G-CSF administered every 12h at doses of 5 or 6 μg/kg provides better yields than 10 μg/kg once daily, without an increase in morbidity. A randomized trial comparing twice daily administration of G-CSF with the standard dose in groups at risk may be valuable. Studies investigating the use of novel agents (such as Plerixafor) could also be considered in donors at risk of poor mobilization.

Disclosures:
No relevant conflicts of interest to declare.