Optimizing the timing of lymphocyte collection after stem cell harvesting in B-cell lymphoma and myeloma patients

Abstract

Background aims: High-quality T-cell apheresis products are essential for the success of cell therapies such as chimeric antigen receptor (CAR) T-cell therapy. However, CAR T-cell therapy is typically reserved for patients with relapsed or refractory B-cell lymphoma and multiple myeloma, in which repeated chemotherapy can deplete naive and T memory stem cell subsets and increase T-cell exhaustion. Early lymphocyte collection-ideally before extensive chemotherapy-may enhance T-cell quality and improve therapeutic outcomes.

Methods: This study evaluated the feasibility of collecting lymphocytes immediately after autologous stem cell harvesting in patients with B-cell lymphoma or multiple myeloma. We analyzed T-cell phenotypes and gene expression profiles from 25 high-risk lymphoma and myeloma patients, comparing samples collected before mobilization chemotherapy with those collected after stem cell harvesting using flow cytometry and RNA sequencing. Key markers related to T-cell differentiation and exhaustion were assessed.

Results: Post-harvest lymphocytes showed a modest increase in effector memory T cells, programmed cell death protein 1 expression and regulatory T cells along with a slight decrease in CD4+ naive T cells/T memory stem cells. Transcriptome analysis revealed no significant differences between the two time points. Although changes in immunophenotyping were statistically significant, they were minor (<5%).

Conclusions: Collection of lymphocytes immediately after stem cell harvesting maintains favorable T-cell characteristics compared with collection from heavily treated relapsed patients. This approach offers a practical and cost-effective strategy using existing vascular access while minimizing patient burden. Our findings support integrating post-harvest lymphocyte collection into T-cell therapy protocols for high-risk patients to improve outcomes and streamline care.

Keywords: T-cell collection; T-cell phenotype; apheresis; chimeric antigen receptor T-cell therapy; stem cell harvesting.