AUTHOR=Juric Mateja Kralj , Ghimire Sakhila , Ogonek Justyna , Weissinger Eva M. , Holler Ernst , van Rood Jon J. , Oudshoorn Machteld , Dickinson Anne , Greinix Hildegard T. 

TITLE=Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

JOURNAL=Frontiers in Immunology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00470

DOI=10.3389/fimmu.2016.00470

ISSN=1664-3224

ABSTRACT=Since the early beginnings, in the 1950’s, 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 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 (BM) other stem cell sources like G-CSF-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 graft-versus-leukemia or anti-tumour 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 summarise the key milestones of HSCT and introduce current developments.