title: New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft-versus-host disease.
abstract: Inhibition of the mechanistic target of rapamycin (mTOR) has been exploited largely both in solid tumour oncology and solid organ transplantation. More recently mTOR inhibitors such as sirolimus and everolimus have been introduced to the field of allogeneic haematopoietic stem cell transplantation where their unique combination of immunosuppressive purposes offering reduced nephrotoxicity and potential antimalignant effects reflect a unique drug profile that has led to their widespread use in both prophylaxis and therapy of graft-versus-host disease (GVHD). On the other hand haematological insufficiency, infectious complications as well as vasculopathies, have been frequently reported as limiting toxicities. Here, we review both the retrospective and prospective experience available to date and stress the need for prospective registration trials to reduce off label use and improve patient safety by optimizing dosing and enhancing pharmacovigilance. Furthermore, we speculate on the future role of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation.
authors.affiliation: Department of Medicine A, Münster University Medical Center, Münster, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lutz
authors.affiliation: Department of Internal Medicine II, Würzburg University Medical Center, Würzburg, Germany. mielke_s@ukw.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
mesh_terms: D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: allogeneic haematopoietic stem cell transplantation; everolimus; graft-versus-host disease; mTOR inhibitors; sirolimus