Abstract
Background aims. Granulocyte–macrophage (GM) colony-stimulating factor (CSF) has been used as an adjuvant in cancer immunotherapy. We tested the hypothesis that GM-CSF (Leukine®; sargramostim) improves immune reconstitution after hematopoietic stem cell transplantation (HSCT) based on our prior in vitro work that demonstrated the pro-inflammatory effects of GM-CSF on dendritic cells (DC). Methods. GM-CSF was administered to donors, along with standard granulocyte (G) CSF, during stem cell mobilization, and to recipients from the day prior to transplant until engraftment. Eighteen patients consented to the GM-CSF+ protocol and were compared with 17 matched controls undergoing HSCT during the same time period (GM-CSF−). Results. Numbers of white blood cells (WBC) and CD34+ stem cells in the graft were comparable to controls. Surprisingly, contrary to our hypothesis, the allogeneic donor graft had significantly decreased numbers of CD3+ T cells and their subsets (CD4+, CD4+ CD45RA+, CD4+ CD45RO+, CD8+ and CD8+ CD45RO+), DC (both myeloid and plasmacytoid) and natural killer (NK) cells (CD16+ CD56+). In the GM-CSF arm, following allogeneic transplantation, the levels of DC, T cells and NK cells did not increase with treatment. Conversely, autologous transplant patients receiving GM-CSF had a higher proportion of DC at the time of engraftment. Conclusions. These findings demonstrate that administration of GM-CSF improves DC reconstitution after autologous rather than allogeneic HSCT.
Acknowledgment
Initial support provided by Immunex, with continued support from Berlex Laboratories. We would like to acknowledge Jose A. Iturraspe for flow cytometric analysis, Lily Tian for the statistical analysis and Drs Alessandra Tzolas for data entry and John R. Wingard and Stratford May for institutional support.
Disclosure of interests: The authors have nothing to disclose.