Age does matter: Examining CD34+ cell numbers and viability increases in donor-derived peripheral blood stem cells

June 12, 2019

Research by Jessica Parker-Raley, Dalton Agee, Naomi Herrera, Rachel Beddard, Pamela Brown Baer and Rogelio Zamilpa

Presented at Childhood Cancer: Research Challenges and the Future of Therapy, March 3-6, 2019

Background/Case Studies:

Peripheral blood stem cells (PBSCs) are used as an alternative to bone marrow and cord blood-derived stem cells for treatment of patients diagnosed with blood disorders including leukemia and lymphoma. PBSCs are the preferred cell source for allogeneic transplantation since large numbers of hematopoietic progenitor stem cells can be collected relatively easily from individual donors using apheresis technology. PBSCs are mobilized into circulation using recombinant, human granulocyte colony stimulating factor (rhG-CSF). Some donors produce more stem cells than others during the mobilization process, thus the biggest challenge associated with PBSC collection is the donor response to rhG-CSF. Accordingly, we aimed to determine what demographic factors influenced mobilization rate in donors who consented to PBSC collection at an apheresis center in south Texas during 2018.

Study Design/Methods:

To address this issue, a retrospective study was designed to determine the influence of donor age and sex on PBSC mobilization in response to rhG-CSF. Young donors (20-29 years old, n= 23, 7F/16M) versus old donors (>30 years old, n =10, 4F/6M) were subjected to a similar mobilization paradigm consisting of a 5-day treatment with rhG-CSF at a concentration of 10 mcg per kg/body weight at an apheresis center in south Texas.

Results/Findings:

Donors from both age groups had similar body weight, and the PBSC products from each donor had similar volumes (p=ns). The average age for the young donor group was 24 compared to a mean of 42 for the old donor group (p<0.05). Interestingly, the precount white blood cell (WBC) at the initial start of collection was significantly higher in the young group (52 x103/ul vs 40 x103/ul, p<0.05). Concomitantly, the final WBC in the PBSC product was increased in the young donor group compared to the old donor group (394 x103/ul vs 324 x103/ul, p<0.05). Furthermore, the total CD34+ cell count was higher in the young donor group compared to the old (695 x106 vs 437 x106, p<0.05) as well as the viable CD34+ absolute cell count (109 cells/ul vs 70 cells/ul, p<0.05).

Conclusion:

These findings indicate that young donors ages 20-29 are the optimal candidates for PBSC donations since their response to G-CSF mobilization is significantly improved compared to older donors (>30 yrs old). The quality of the PBSC product in young donors is optimal compared to the old donors as indicated by the increased WBC counts, CD34+ counts and CD34+ cell viability. No significant differences were found when the young age group was analyzed by sex further indicating that both sexes within the young age group respond similarly to G-CSF.

Summary:

Comparison between younger and older donors’ PBSC products indicate that:

  • Young WBC yields are significantly higher
  • Young Total CD34+cell counts are higher
  • Absolute CD34+cell viability counts are elevated in the young
  • Age does matter when it comes to donor PBSCs

Methods:

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Figure 1. Study Design Comparing Young Donors vs Old Donors

 

 

 

 

 

 

 

Results:

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Figure 2. (A) Representative PBSC recipient diagnoses and (B) image of a PBSC product shipped for transplant.

 

 

 

 

 

 

 

 

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Figure 3. (A) Donor body weight and (B) PBSC product volume were similar among young vs old donor groups (p=ns).

 

 

 

 

 

 

 

 

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Figure 4. (A) WBC precounts and (B) WBC final counts were significantly higher in the young donor group compared to the old indicating that young donors represented better to G-CSF (p<0.05).

 

 

 

 

 

 

 

 

 

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Figure 5. (A) Flow cytometry analysis of the PBSC product indicated that young donors yield higher total numbers of CD34+ cells (p<0.05).

 

 

 

 

 

 

 

 

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Figure 6. (A) Flow cytometry analysis of the PBSC product using 7-AAD indicated that the absolute CD34+viable cells counts in young donor products are significantly higher (p<0.05).