Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant.

Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.

Favorable outcome after infusion of coagulase-negative staphylococci-contaminated peripheral blood hematopoietic cells for autologous transplantation.

Bacterial contamination of peripheral blood hematopoietic cells collected for autologous bone marrow transplantation occurs sporadically. Although transfusion of contaminated hematopoietic cells without adverse clinical sequelae has been reported, detailed guidelines for transfusing cells with contamination are not available. We report a case of autologous hematopoietic cell transplantation that necessitated using multiple aliquots of peripheral blood hematopoietic cells known to be contaminated with coagulase-negative Staphylococcus bacteria. Prophylactic intravenous antibiotic therapy was given with the infusion of contaminated hematopoietic cells. The patient had positive results on a blood culture, but engraftment was successful, and serious adverse effects did not occur. With appropriate microbial identification and prophylactic antibiotic therapy, contaminated hematopoietic products can be safely infused when necessary with a good clinical outcome.