History and legal aspects of bone marrow donor banks in Brazil

INTRODUCTION: Bone marrow transplants primarily depend on people who previously registered to be donors. From then on, the search for compatibility between donor and recipient begins. OBJECTIVE: To describe the historical landmarks and the legal apparatus of bone marrow donor banks in Brazil based on an integrative review. METHODS: LILACS database and PubMed and SciELO journals were used. The term bone marrow transplantation was the descriptor. Eligibility criteria were: articles with the theme of Bone Marrow Transplantation (BMT) and studies carried out on the national territory. RESULTS: A total of 88,855 articles were identified, among which 185 met the eligibility criteria. After they were thoroughly read, 14 articles were selected. The studies pointed out fragments that dealt with important historical landmarks for the establishment of bone marrow transplantation as a conventional treatment for oncohematological diseases. CONCLUSION: The use of BMT has a history of more than thirty years in Brazil. However, none of the articles identified specifically addresses the historical content of bone marrow transplantation.

Bone marrow transplantation in the United Kingdom - past, present and future.

Bone marrow transplantation (BMT) has evolved over the last 60 years from a pioneering treatment fraught with unknown factors and complications to a widely practiced standard of care that has saved the lives of countless individuals with malignant and non-malignant conditions. Over this period, transplanters in the UK have made a significant international contribution to the field through cutting edge clinical and laboratory research. Today, stem cell transplantation in the UK continues to advance through rigorous and innovative clinical trials which focus on improving outcome by reducing transplant toxicity and the risk of disease relapse. In this review, we start with a personal view of the early years of BMT in the UK, document the many seminal accomplishments in the field of BMT which took place in the UK, and end with a look towards the future of BMT, in the UK and worldwide.

The history of bone marrow in orthopaedic surgery (part I trauma): trepanning, bone marrow injection in damage control resuscitation, and bone marrow aspiration to heal fractures.

PURPOSE: One of the oldest procedures performed by man is trepanning of the bone and yet it was only in the last 40 years that bone marrow aspiration has been used to treat nonunion disorders. MATERIAL AND METHODS: These advances were possible due to improvements in instruments and in techniques to make holes in the bone, an history that began with skull trephinations around 8000-10,000 years ago, and continued with sternum bone marrow injection for trauma resuscitation in the beginning of the twentieth century; this procedure had improved at the beginning of the twenty-first century to allow pelvis bone marrow aspiration for the treatment of nonunion. RESULTS: Trephined skulls from antiquity have been found in many parts of world, showing that trephining was ancient and widespread. Beginning with Neolithic period and the pre-Columbian Andean civilizations, the authors have traced the development of this surgical skill by describing the various surgical tools used to perform holes in the skull. These tools (trephines or trepan) were proposed at the end of the nineteenth century to study the bone marrow. At the beginning of the twentieth century, the sternum became the center of interest for the "in vivo" study of the bone marrow and the fluid injection in the sternum's bone marrow was described for resuscitation from shock during the World War II. With the introduction of plastic catheters and improved cannulation techniques, the need for intraosseous infusion as an alternative route for intravenous access diminished and sometimes abandoned. However, during the mid-1980s, James Orlowski allowed renaissance of the use of intraosseous infusion for paediatric resuscitation. Since then, this technique has become widespread and is now recognized as an alternative to intravenous access in adult emergencies; particularly, the intraosseous access has received class IIA recommendation from the Advanced Trauma Life Support program supported by the American College of Surgeons Committee on Trauma and bone marrow infusion is now recommended for "Damage Control" resuscitation. Although the pelvis bone contains half of the body's marrow volume, it was only in 1950 that the pelvis was proposed as a source for bone marrow aspiration and bone marrow-derived mesenchymal stem cells to improve healing of fractures. CONCLUSION: It will be many years before doing holes in the bone as orthopaedic trauma procedure will be relegated to the annals of history.

Bone Marrow Transplantation 1957-2019.

Clinical bone marrow transplantation started in 1957 at a time when remarkably little was known about hematopoietic stems cells, immune responses to transplants or the identity of transplant antigens. This review will delineate the substantial increase in knowledge about these three areas gained between then and 1992 when the Ceppellini School course on Bone Marrow Transplantation was held, along with the progress made in clinical application, as well as the stumbling blocks that remained to be overcome by further research to advance knowledge. It will outline the significant progress made between 1992 and the present year, 2019, and the remaining problems.

To condition or not to condition-That is the question: The evolution of nonmyeloablative conditions for transplantation.

In 1985, Eugene Cronkite and his colleagues published, in Experimental Hematology, data indicating that five consecutive "transfusions" of large numbers of marrow cells significantly increase the number of donor-derived cells detected by day 10 of a spleen colony-forming assay, the most primitive hematopoietic cells detectable at that time, present in the host for as long as 2 months posttransfusion (Cronkite EP, Bullis JE, Brecher G. Marrow transfusions increase pluripotent stem cells in normal hosts. Exp Hematol 1985;13:802-805). These data provided the first evidence that donor hematopoietic stem cells (HSCs) may persist in vivo for some time in recipients when transfused and not transplanted, that is, not subjected to treatments that deplete their marrow niches of endogenous HSCs. The limited technology available at the time prevented Dr. Cronkite from pursuing this observation into the development of nonmyeloablated transplantation procedures, and his experiment, as well as the term bone marrow transfusion, has since been long forgotten. In recent years, the scientific need to clarify HSC functions in nonstressed hosts and the clinical need to develop transplantation procedures with levels of morbidity/mortality acceptable for curing inherited hematologic disorders have inspired the search for nonmyeloablative transplantation procedures, including methods that "outcompete" endogenous host HSCs such as those pioneered by Dr. Cronkite's experiments using high transfusion doses. This review describes the technical progress made since Dr. Cronkite's insightful work, which has finally found its path to the clinic.

History of graft-versus-host disease.

Nuclear warfare at the end of World War II inspired Dick W. van Bekkum to study total-body irradiation (TBI) in animal models. After high-dose TBI, mice died from "primary disease" or bone marrow (BM) aplasia. Intravenous administration of allogeneic BM cells delayed mortality but did not prevent it. Initially the delayed deaths were said to be caused by "secondary disease," which was later renamed graft-versus-host disease (GvHD). GvHD is caused by donor T lymphocytes that destroy recipient cells in skin, intestinal mucosa, bile ducts, and lymph nodes. GvHD is opposed by host-versus-graft disease (HvGD), in which host T lymphocytes destroy the administered allogeneic BM cells, including the administered T lymphocytes of the BM donor. In 1960, van Bekkum became the director of the Radiobiological Institute of the Dutch Organization for Applied Scientific Research TNO, Rijswijk, The Netherlands, where he built a multidisciplinary team that defined the variables controlling the outcome of a BM transplant. The team published their early results in the Journal of Experimental Hematology [1981;9:904-916 and 1956;4:482-488]. Later, protocols were established for BM transplantation (BMT) in patients with severe combined immunodeficiency disease, leukemia, lymphoma, and other diseases of the hematopoietic system. This review honors the scientific contributions made by Dick van Bekkum and his team in defining the four dominant variables for improving the therapeutic ratio of allogeneic BMT and in fostering the international collaboration necessary to translate this knowledge into current clinical practice.

Historique de l'immunothérapie. Changement de paradigme ?

HISTORY OF IMMUNOTHERAPY. PARADIGM CHANGE?: Born at the dawn of the 20th century with W.B. Coley's intratumoral injections of bacteria, cancer immunotherapy was built on the corpus of the immune surveillance theory in 1957, modified by R.D. Schreiber in 2004. Scientific knowledge and technological advances have allowed it to become efficacious and to expand in the 21st century as the 4th and most important pillar of cancer treatment.

Transient mixed chimerism for allograft tolerance.

Mixed chimerism discovered in Freemartin cattle by Ray Owen 70 years ago paved the way for research on immune tolerance. Since his discovery, significant progress has been made in the effort to induce allograft tolerance via mixed chimerism in various murine models. However, induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex mismatched humans. Chimerism induced in humans tends to either disappear or convert to full donor chimerism, depending on the intensity of the conditioning regimen. Nevertheless, our studies in both NHPs and humans have clearly demonstrated that renal allograft tolerance can be induced by transient mixed chimerism. Our studies have shown that solid organ allograft tolerance via transient mixed chimerism 1) requires induction of multilineage hematologic chimerism, 2) depends on peripheral regulatory mechanisms, rather than thymic deletion, for long-term maintenance, 3) is organ specific (kidney and lung but not heart allograft tolerance are feasible). A major advantage of tolerance induction via transient mixed chimerism is exclusion of the risk of graft-versus-host disease. Our ongoing studies are directed toward improving the consistency of tolerance induction, reducing the morbidity of the conditioning regimen, substituting clinically available agents, such as Belatacept for the now unavailable anti-CD2 monoclonal antibody, and extending the protocol to recipients of deceased donor allografts.