title: Milestones of Hematopoietic Stem Cell Transplantation - From First Human Studies to Current Developments.
abstract: Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments.
authors.affiliation: BMT, Department of Internal Medicine I, Medical University of Vienna , Vienna , Austria.
authors.forename: Mateja Kralj
authors.initials: MK
authors.lastname: Juric
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg , Regensburg , Germany.
authors.forename: Sakhila
authors.initials: S
authors.lastname: Ghimire
authors.affiliation: Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover , Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Ogonek
authors.affiliation: Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover , Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Weissinger
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg , Regensburg , Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: van Rood
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: Hematological Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Dickinson
authors.affiliation: Division of Hematology, Medical University of Graz , Graz , Austria.
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
keywords: HLA typing; conditioning; hematopoietic stem cell transplantation; milestones; stem cell source