Implementing a new conditioning regimen for allogeneic stem celltransplantation: objectives and key factors for an experimental approach

The field of hematopoietic stem cell transplantation (HSCT) has evolved rapidly from standard conditioning with cyclophosphamide (Cy), total body irradiation (TBI) and bone marrow (BM) as a source, to many diverse conditioning regimens followed by manipulated grafts.1 Standard conditioning and graft A conventional transplant remains the therapy of choice for younger patients without comorbidities in the absence of results from prospective, controlled trials. 2 A conventional conditioning is defined as a package of full myeloablation based on high doses of Cy-TBI or Cy-busulfan. Such preparative regimen is followed by infusion of marrow HSC or G-CSF-mobilised peripheral blood progenitor cells (PBSC) from an HLA-matched related or unrelated donor. For allogeneic HSCT, both sources are used as a standard, although both methods have their specific peculiarities. Peripheral blood stem cells are associated with more rapid engraftment in the recipient and an increased incidence of chronic GVHD, compared to BMT. However, unfractionated allogeneic HSCT following high-dose chemoradiotherapy is associated with a considerable risk of acute graft-versus-host disease (GVHD), leading to significant morbidity and mortality. Age is an important prognostic factor for treatment-related mortality (TRM) which increases by each decade both in HLA-identical sibling transplants and more so for alternative donor transplants.