In Vitro Expanded Umbilical Cord Blood T Cells Used for Donor Lymphocyte Infusions after Umbilical Cord Blood Transplantation

Umbilical cord blood (UCB) is an alternative graft source for hematopoietic stem cell transplantation and has been shown to yield results comparable to transplantation with other stem cell sources. Donor lymphocyte infusion (DLI) is an effective treatment for relapsed hematological malignancies after hematopoietic stem cell transplantation. However, DLI is not available after UCB transplantation.

In this study, in vitro cultured T-cells from the UCB graft were explored as an alternative to conventional DLI. The main aim was to study the safety of treatment with the cultured UCB T-cells, as cell products prepared in this particular manner has not been used before. We also wanted to study potential benefits of the treatment.

The cultured UCB T cells (UCB DLI) were given to four patients with mixed chimerism (n = 2), minimal residual disease (n = 1) and graft failure (n = 1). No adverse reactions were seen at transfusion. Graft-versus-host disease (GVHD) is a known risk in conventional DLI treatment. We thus carefully assessed the included patients for signs of GVHD. Three of the patients did not show any signs of GVHD after treatment with UCB DLI. However, GVHD could not be wholly excluded in the last patient. The symptoms were, however, not consistently in temporal association with the treatment, and the patient also had a severe adenovirus infection that could explain the symptoms. In the patient with minimal residual disease, the malignant cell clone was detectable shortly before infusion but undetectable at treatment and for 3 months after infusion. In one patient with mixed chimerism, the percentage of recipient cells decreased in temporal association with UCB DLI treatment.

In summary, we saw no certain adverse effects of treatment with UCB DLI. Events that could indicate possible benefits were seen but with no certain causal association with the treatment.