Biotherapies, Cellular Therapies, and Immunotherapies
Carmel Sergio, MBA, MLS(ASCP)CM
Mayo Clinic, Florida, United States
CD34+ Selection of hematopoietic progenitor cells (HPCs) represents a significant opportunity in the treatment of autoimmune diseases. This process involves isolating mobilized CD34+ stem cells from a patient's peripheral blood and reintroducing them to the autologous donor after marrow preparation for transplant. These CD34+ selected transplants can lead to the regeneration of a more tolerant immune system after thymic rebound, reducing disease activity, and improving the quality of life for patients. Here we report the characteristics of CD34+ Selection in 29 patients with autoimmune disease using the CliniMACS CD34 Reagent System with successful post-transplant engraftment.
Study
Design/Methods:
We performed 47 CD34+ Selections on 43 HPC(A) products using the CliniMACS Plus from 29 patients. Table 1 shows the following data gathered for each Selection. Samples were drawn prior to and after selection in the processing lab. Time to engraftment was determined by days to absolute neutrophil count of 0.5 x10(9)/L and platelet count of >20,000 x10(9)/L for 7 days without transfusion support.
Results/Findings:
Mean recovery from 47 CD34+ Selections is 63.83% (SD ± 17.78%). 8 CD34+ Selections had less than 50% recovery from the 47 CD34+ Selections. 2 were repeated and recovery on the repeats were greater than 50%. 2 products were divided for enrichment given excess cellularity within the collection. The mean neutrophil engraftment is 11.41 days and platelet engraftment is 14.40 days for CD34+ enriched infusions. The mean CD34+ cells/kg dose is 4.13 (SD ± 1.70) per transplant.
Conclusions:
CD34+ enriched products are used to help manage certain patients with autoimmune disease including Scleroderma, Crohn’s disease, Mixed Connective Tissue disease, antiphospholipid syndrome, and Cogan’s syndrome refractory to conventional immunosuppressive therapies. From 2021 to 2023, the mean neutrophil and platelet engraftment, respectively, for conventional HPC(A) transplants at our transplant program was 15.75 days and 20.25 for 200 allogeneic transplants and 12.5 days and 17 for 394 autologous transplants. Compared to conventional autologous transplants, CD34+ selected transplants resulted in faster engraftment by 1.09 days. Explanation is a higher mean cell dose or likelihood of less marrow damaging therapy prior to transplant. Furthermore, the institution has implemented more stringent approval criteria for these transplant candidates. CD34+ selected transplant offers a promising alternative for patients who have failed traditional immunosuppressive therapies to promote lasting disease stabilization and remission. At our middle-sized transplant program, CD34+ selected autologous transplants resulted in successful engraftment with standard transplant dosing. We continue to improve our internal processes given FTE time demands of the process and reagent costs.