This week we begin a 3-part blog series on the intricacies of optimizing the quality of cell therapy starting materials. Cell and gene therapies have the potential to transform healthcare. Successfully bringing these therapies to the market, however, is a challenge. The intrinsic variability of living cells carries an increased risk and cost to therapeutic development not encountered with traditional medicine. Those risks are being countered with innovative strategies and technologies that experts hope will bridge the translational gap between research and industry.
Dealing with Donor Variability
Every cell therapy starts with a donor. For this very reason, each cellular therapeutic begins with the challenge of addressing the impact of donor variability on apheresis starting material. Why are some people “good” donors while others are not? What can be done to maximize the quality of apheresis material when healthy donor collection isn’t optimal? As the leading provider of human cellular starting material, we answer these questions on a daily basis.
The number of white blood cells (WBC) that are collected from a donor depends on a number of different variables. Total WBC counts are known to be higher in young children than adults and tend to decrease with age, an effect that becomes significant over the age of 65 . There are additional lifestyle or genetic factors that can potentially impact white blood cell count. For example, a higher BMI correlates with higher complete white blood cell counts . It stands to reason that someone who is larger and has a higher total blood volume can donate a greater number of WBCs. Collection center experts must be cautious, however, that higher BMI is not due to encroaching disease states such as metabolic syndrome or diabetes, which can negatively impact a donor’s physiology.
Contributing Factors to White Blood Cell Count
Lifestyle demographics can be used as a predictive factor of leukocyte yield when assessing donors. Studies have shown that sleep deprivation, fatigue, and physical or psychological stress (all of which are related to inflammation effects) are positively correlated with total WBC and neutrophil counts .
A donor who engages in smoking will often have higher than average WBC counts , while a donor who engages in moderate alcohol consumption can have lower WBC counts . Excessive drinking, however, results in abnormal WBC counts due to tissue damage .
Diet can impact white blood cell counts as well; increases in dietary copper and iron are associated with a decrease in WBC count, while increases in vitamin B12 increased WBC count. Poor overall nutrition has been shown to be associated with low white blood cell counts and in severe cases, can lead to bone marrow atrophy .
An experienced apheresis nurse understands that personal issues and lifestyle do impact physiology, even though the impact may be temporary. Positive donor interaction and encouragement toward healthy practices can help optimize apheresis yields while fostering good donor relationships.
As the number of cell and gene therapies in clinical trial grows, access to high-quality, healthy donor material is increasingly important. A large, diverse donor network and extensive experience in dealing with donor variability can help ensure that access. But ensuring quality goes further than good donor management. In part 2 of this series, find out how apheresis methodology and best practices are critical to maximizing the yield and purity of cell therapy starting materials.
- Nah E-H., et al. Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea. Ann Lab Med. 38: 503-511. (2018).
- Jamshidi L., and Seif A. Association Between Obesity, White Blood Cell and Platelet Count. Zahedan J Res Med Sci. 19(2): e4955. (2017).
- Ackerman K. et al. Diurnal Rhythms in Blood Cell Populations and the Effect of Acute Sleep Deprivation in Healthy Young Men. Sleep. 35(7); 933-940F. 2012.
- Pedersen K. M., et al. Smoking and Increased White and Red Blood Cells: A Mendelian Randomization Approach in the Copenhagen General Population Study. Arterioscler Thromb Vasc Biol. 39: 965-977. 2019.
- Nakanishi N., et al. Association of alcohol consumption with white blood cell count: a study of Japanese male office workers. Journal of Internal Medicine. 253: 367–374. 2003.
- Varghese S., et al. Impact on the hematopoietic system by alcoholism and the influence of duration of consumption. National Journal of Physiology, Pharmacy and Pharmacology; Surat 9(8): 742-745. 2019.
- Mehler P.S., and Brown C. Anorexia nervosa-medical complications. Journal of Eating Disorders. 3:11. 2015.