Thymopoiesis following allogeneic stem cell transplantation: new possibilities for improvement

Abstract

Treatment related mortality (TRM) has restricted the application of allogeneic hematopoietic stem cell transplantation (allo-SCT) as a treatment modality for patients with a variety of malignant and non-malignant hematological disorders. TRM is mainly caused by severe opportunistic infections, due to an impaired immune reconstitution. The extreme slow recovery of newly developed, donor stem cell derived naive T-cells is currently considered to be the most important determinant of the impaired immune competence after allo-SCT. Therefore, enhancing naive T-cell recovery following allo-SCT by improving thymopoiesis has recently gained new interest. Possible strategies to improve thymopoiesis may include approaches to protect the nursing stromal compartment and approaches to directly stimulate the differentiation and proliferation of T-cell progenitors intra-thymically. Among the latter is interleukin-7 (IL-7), which has appeared promising in preclinical experimental settings and is expected to enter early clinical studies soon. Keratinocyte growth factor (KGF) is an epithelial growth factor that may protect the thymic epithelium and thereby may preserve it's support of thymopoiesis. KGF has been evaluated clinically in the setting of autologous stem cell transplantation and studies in the setting of allo-SCT are awaited in the near future.