University of Minnesota Masonic Children's Hospital Archives

2014

Impact Grant

Dr. Lucie Turcotte

Minneapolis, MN

Autologous transplantation is utilized in the setting of many high-grade pediatric malignancies. This therapy involves giving marrow ablative doses of chemotherapy, followed by autologous stem cell rescue, resulting in a prolonged period of immune system perturbation and reconstitution. While this therapy offers the potential of cure in otherwise difficult to treat diseases, it can be associated with both short- and long-term health consequences. While much research has been performed looking at late health effects among cancer survivors, little attention has focused specifically on autologous transplant recipients. Cardiometabolic syndrome (CMS) is a known long-term adverse health effect among childhood cancer survivors and has also been described following hematopoietic cell transplantation (HCT). Previous research investigating the underlying etiology of CMS in the survivor population has primarily looked at the role of specific therapies and their association with subsequent development of CMS, and the majority of existing literature has focused on individuals receiving either standard dose chemotherapy or allogeneic HCT. Interestingly, recent data in the non-cancer survivor population has shown that pathophysiology of CMS involves a dynamic interaction between the immune system and adipose tissue. Accumulation of fat results in alteration in adipokine production and in the skewing of innate immune cells to produce pro-inflammatory cytokines. Considering this and the significant and long-term perturbation in immune homeostasis associated with autologous stem cell transplantation, we hypothesize that immune dysregulation following autologous transplant is a significant contributor to post-transplant CMS. We aim to better define the incidence of CMS among autologous transplant survivors and to understand whether differences exist in adipokines, inflammatory cells, and pro-inflammatory cytokines between: 1) autologous stem cell transplant recipients who develop CMS, 2) non-transplanted individuals with CMS, as well as 3) healthy individuals without CMS.