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An incorrect percentage value has been referred to in chapter 41.

HSCT has evolved from a field that was declared dead in the 1960s to the amazing clinical results obtained today in the treatment of otherwise fatal blood disorders.

“Only he/she who knows the past has a future” is a proverb attributed to Wilhelm von Humboldt (1767–1835), a great historian, scientist, and philosopher (Spier ). It appears as an ideal introduction to a chapter on the history of EBMT. The context by which HSCT evolved in the middle of last century fits with modern views on history. The novel “big history” concept attempts to integrate major events in the past, beginning with the “big bang” up to today’s industrial revolution number IV (Spier ). According to this model, nothing “just happens.” Progress occurs when the conditions fit, at the right time and at the right place.

Bone marrow donor registries (hereinafter referred to as registries) have been playing an important role in developing the treatment of HSCT for more than four decades. In 1974, the world’s first registry was founded by Shirley Nolan in London. Shirley’s son, a 3-year-old, Anthony, had been diagnosed with Wiskott-Aldrich syndrome and needed a transplant. Following the example of Anthony Nolan, a large number of registries have been established around the world, mainly in the late 1980s to early 1990s and have increased over the years.

>HSCT is an advanced therapeutic intervention that is required for a number of malignant and nonmalignant medical conditions, often for critically ill patients. The establishment of an HSCT program requires the efforts of experienced and appropriately trained personnel to lead the program. Clearly, this also requires financial, legal, ethical, and other institutional support. For newly starting programs, it would be essential to identify minimal requirements for establishing an HSCT unit in order to optimize resource utilization as well as maintain safe patient care. While these minimal requirements also apply to well-established units, its structure helps to understand and implement additional steps for larger units which plan to offer additional transplant services and have access to more resources.

The complexity of HSCT as a medical technology and the frequent need for close interaction and interdependence between different services, teams, and external providers (donor registries, typing laboratories, etc.) distinguish it from many other medical fields. Approximately 20 years ago, this complexity led to efforts by transplantation professionals to standardize processes based on consensus as a way to better manage inherent risks of this treatment. HSCT was, and continues to be, a pioneer in the area of quality and standards.

The analysis of data describing the outcomes of patients who have received an HSCT is not only fundamental to assessing the effectiveness of the treatment but can provide invaluable information on the prognostic role of disease and patient factors. Thus, the appropriate analysis and understanding of such data are of paramount importance. This document provides an overview of the main and well-established statistical methods, as well as a brief introduction of more novel techniques. More insight is provided in the (Iacobelli ).

Hematopoiesis—from the Greek term for “blood making”—is the adaptive process by which mature and functional blood cells are continuously replaced over the entire lifetime of an individual. Erythrocytes, platelets, and the various subsets of leukocytes all have finite although different life spans. As a consequence, the daily production of red blood cells, platelets, and neutrophils in homeostatic conditions amount to more than 300 billion cells.

The array of cellular players involved in the biology of HSCT clearly extends beyond HSC themselves and, in the case of transplantation from allogeneic sources, importantly includes cells of the innate and adaptive immune system. Historically, the discovery of the HLA system and the functional characterization of the different immune cell types had a transformational impact on our current understanding of the pathobiological of allo-HSCT (rejection, GVHD, the GVL effect). This body of knowledge coupled to the most recent of biotechnology nowadays allows us to design strategies for in vivo stimulation or adoptive transfer of specific immune cell types with the potential to dramatically improve transplantation outcome.

Immune-mediated rejection of tissue allografts was first described in 1945 by the British immunologist Peter Medawar, followed by the discovery of the major histocompatibility complex (MHC) carrying the histocompatibility genes by Peter Gorer and George Snell in 1948, and of the human leukocyte antigen (HLA) molecules by Jean Dausset, Jon van Rood, and Rose Payne a decade later (Thorsby ). The importance of these discoveries was recognized by the Nobel Prices in Physiology and Medicine to Medawar, Snell, and Dausset in 1960 and 1980, respectively. Since then, the MHC has emerged as the single most polymorphic gene locus in eukaryotes, with 17,695 HLA alleles reported to date in the IMGT/HLA database, Release 3.31.0, 2018/01/19 (Robinson et al. ). While the main barrier to successful tissue grafting remain the HLA incompatibilities, also non-HLA polymorphisms have been recognized as important players, in particular minor histocompatibility antigens (mHAg), killer immunoglobulin-like receptors (KIR), and other polymorphic gene systems (Dickinson and Holler ; Gam et al. ; Heidenreich and Kröger ; Spierings ).