Determining Donor Eligibility for Donor Lymphocyte Infusions Aliquoted from a Product Intended for Transplantation
By Patrick J. Hanley, PhD
Chair, FACT Education Committee
Chief & Director, Cellular Therapy Program
Associate Professor of Pediatrics
Center for Cancer and Immunology Research
Children’s National Hospital & The George Washington University
Haploidentical hematopoietic progenitor cell (HPC) transplantation has increased drastically over the past five years. One reason for this increase is the introduction of T cell Receptor (TCR) α/β and CD19 depletion. In this manufacturing process, the α/β T cells and CD19 B cells are depleted, leaving γ/δ T cells, CD34+ stem cells, and other immune cells that are infused into the patient. The hypothesis is that the γ/δ T cells will provide an anti-tumor effect (in the case of malignancies) and anti-viral immunity, while the lack of α/β T cells will reduce the incidence of graft versus host disease (GVHD). However, the very limited CD3+ alpha beta T cell dose (often less than 1×105 CD3+ α/β /kg) may leave the recipient more susceptible to viral infections, or even engraftment failure. Therefore, clinicians often request that the cell processing facility cryopreserve aliquots of the α/β T cell-containing fraction to be used as a potential donor lymphocyte infusion (DLI).
Donor eligibility gurus may already see the conundrum: the TCR α/β/CD19-depleted cellular therapy product is an HPC product, for which donor infectious disease testing is allowed by the U.S. Food and Drug Administration (FDA) up to 30 days prior to collection; DLI is considered a therapeutic, leukocyte-rich tissue and therefore requires infectious disease testing to be done before or after seven days from collection. Programs can be conservative and simply draw samples for testing within seven days to cover both HPC products and therapeutic products. However, this may not align with the existing process for work-up of the donor in preparation for donation. In some cases, it may require an additional blood draw, which is not in the best interest of the donor.
Based on previous clarification from the FDA (which was confirmed by the FACT office in August 2021), the most straightforward way to address this issue is to recognize that separate eligibility determination is NOT required for the T cell product used as DLI if the lymphocytes were collected as a part of the HPC collection. When the donor of the HPC product is screened and tested in accordance with regulations and determined to be eligible for donation, the donor eligibility determination also applies to the remaining portion of the same product that is used for subsequent therapy.
The following example was presented during a FACT webinar by Safa Karandish, MT(ASCP) from the FDA in 2015 as part of a presentation titled, “FDA presents: Using Donor Screening and Testing to Determine Donor Eligibility,” which can be found on the FACT website at: http://www.factweb.org/forms/store/ProductFormPublic/fda-presents-using-donor-screening-and-testing-to-determine-donor-eligibility.As most of us can attest, with a number of nuances and exceptions to the regulations, donor eligibility determination can be complicated. It’s a relief to hear that in the case of labeling products for DLI from a product collected for an HPC transplant, the regulations are straightforward and the DLI product does not require separate donor eligibility determination.