Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

Concise review: umbilical cord blood transplantation: past, present, and future.

Allogeneic hematopoietic stem cell transplantation is an important treatment option for fit patients with poor-risk hematological malignancies; nevertheless, the lack of available fully matched donors limits the extent of its use. Umbilical cord blood has emerged as an effective alternate source of hematopoietic stem cell support. Transplantation with cord blood allows for faster availability of frozen sample and avoids invasive procedures for donors. In addition, this procedure has demonstrated reduced relapse rates and similar overall survival when compared with unrelated allogeneic hematopoietic stem cell transplantation. The limited dose of CD34-positive stem cells available with single-unit cord transplantation has been addressed by the development of double-unit cord transplantation. In combination with improved conditioning regimens, double-unit cord transplantation has allowed for the treatment of larger children, as well as adult patients with hematological malignancies. Current excitement in the field revolves around the development of safer techniques to improve homing, engraftment, and immune reconstitution after cord blood transplantation. Here the authors review the past, present, and future of cord transplantation.

Umbilical cord blood transplantation: the first 25 years and beyond.

Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.

Human cord blood applications in cell therapy: looking back and look ahead.

INTRODUCTION: Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed. AREAS COVERED: UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed. EXPERT OPINION: Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.

Milestones in umbilical cord blood transplantation.

Much has been learned about umbilical cord blood (UCB) since the first human cord blood transplant was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation and distribution of UCB for allogeneic haematopoietic stem cell transplantation. UCB has now become one of the most commonly used sources of haematopoietic stem cells for allogeneic transplantation. Today, a global network of cord blood banks and transplant centres has been established with a large common inventory, allowing for more than 20000 transplants worldwide in children and adults with severe haematological diseases. Several studies have been published on UCB transplant, assessing risk factors such as cell dose and human leucocyte antigen mismatch. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality and include the use of reduced-intensity conditioning regimen, intra-bone injection of cord blood cells, double cord blood transplants or ex vivo expansion of cord blood cells. The absence of ethical concern and the unlimited supply of cells explain the increasing interest of using UCB for developing regenerative medicine.

Milestones in umbilical cord blood transplantation.

Since the first human cord blood transplant, performed in 1988, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. Umbilical cord blood (UCB) has now become one of the most commonly used source of hematopoietic stem cells for allogeneic transplantation. Today a global network of cord blood banks and transplant centers has been established for a common inventory with an estimated 600,000 UCB have been banked and more than 20,000 UCB units distributed worldwide for adults and children with severe hematological diseases. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. The absence of ethical concern, and the unlimited supply of cells explain the increasing interest of using cord blood for developing regenerative medicine.

Umbilical cord blood transplantation: the first 20 years.

In October 1988, the world's first umbilical cord blood transplant (UCBT) was performed. Despite considerable skepticism initially by both scientists and clinical specialists in the field, umbilical cord blood (UCB) has now become one of the most commonly used sources of hematopoietic stem cells (HSCs) for allogeneic transplantation. Today, an estimated 600,000 UCB units have been banked and 20,000 UCB units have been distributed worldwide for both adults and children with life-threatening malignant and nonmalignant diseases. During this first generation of UCBT, substantial advances have been made resulting in better outcomes for our patients. UCB serves as an extraordinary example of translational medicine at its best, where clinical problems compel scientists to move basic discoveries into novel therapeutic approaches. This chapter briefly summarizes the highpoints of the history of UCBT with speculations as to what the next generation of research promises to discover.

Umbilical cord transplantation: epilogue.

The field of cord blood transplantation has come a long way since the first transplant more than 20 years ago. Advancements in the field will require continuing efforts to better understand hematopoietic stem and progenitor cell function and engraftment. Cautious optimism is inherent in the potential relevance and applicability of nonhematopoietic stem and progenitor cell types found in cord blood, and induced pluripotent stem cells generated from cord blood cells. Rigorous investigations and close interactions between scientific and clinical investigators are required to translate human in vitro and animal in vivo findings into clinical utility.

Cord blood banking: a historical perspective.

Umbilical cord blood (UCB) contains stem and progenitor cells capable of restoring haematopoietic and immunological function in vivo. UCB is currently used as an alternative source of haematopoietic stem cells for transplantation in patients suffering from haematological malignancies, bone marrow failures and inherited metabolic disorders. In order to facilitate transplantation, large repositories of frozen cord blood units (CBUs) from altruistic donations have been established in many parts of the world and to date there are more than 300,000 units stored worldwide. These products have been banked under stringent quality conditions, in order to ensure their safety and efficacy. The development and evolution of the policies and procedures currently in use in cord blood banking have been largely influenced by the clinical results of cord blood transplantation. This review aims to provide a historical overview of the various developments in the field of cord blood banking from its inception, highlighting the relevant aspects in their collection, banking and release that are known to influence the clinical outcome of these transplants.

History of cord blood transplantation.

Since the first human cord blood transplant, performed 20 years ago, cord blood banks have been established worldwide for the collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. A global network of cord blood banks and transplant centers has been established for a common inventory and study of clinical outcomes. Results of unrelated allogeneic cord blood transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated BM transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of GVHD and better long-term immune recovery resulting in a similar long-term survival. Several studies have shown that the number of cells is the most important factor for engraftment, although some degree of HLA mismatches is acceptable. Developments are expected to facilitate engraftment, including ex vivo expansion of stem cells, intrabone injection of cord blood cells and double cord blood transplants. In addition to hematopoietic stem cells, cord blood and placenta contain a large number of nonhematopoietic stem cells. In the absence of ethical concern, the unlimited supply of cells explains the increasing interest of using cord blood for developing regenerative medicine.

Private cord blood banking: current use and clinical future.

International private umbilical cord blood banking has expanded rapidly in recent years since the first cord blood transplant which was 20 years ago. Private companies offer parents the opportunity to store umbilical cord blood for the possible future use by their child or other family members. The private cord blood industry has been criticised by a number of professional bodies including the EU Ethics Committee, the Royal College of Obstetrics and Gynaecology, the Royal College of Midwives and the US College of Paediatrics. This review presents the arguments from the opponents of private cord blood banking, and then makes the case for private cord banking based on the latest scientific and clinical evidence.

History of the clinical use of umbilical cord blood hematopoietic cells.

The first cord blood (CB) transplant was performed in 1988 in a patient with Fanconi anemia. The donor was his HLA-identical sister who was known by pre-natal diagnosis to be HLA identical and not affected by the Fanconi mutation. The CB was collected and cryopreserved at birth. The transplant was successful without GvHD and the patient is currently alive and free of disease more than 15 years after transplant, with full hematologic and immunologic donor reconstitution. At the time of the first transplant, little was known about the biologic properties of CB cells and it was thanks to the pioneering work of H. E. Broxmeyer and E. A. Boyse, who studied the progenitor cell content of CB, and of A. D. Auerbach, who realized the pre-natal diagnosis of Fanconi anemia, that this transplant was possible. Since this first transplant, many questions have been answered but others are still open for further research. For example: would a single CB unit contain enough stem cells to permanently engraft children and adults? Would maternal cell contamination in fetal blood engraft and give severe GvHD? What are the immunologic properties of CB cells? How does it interfere with GvHD, GvL and immune reconstitution? Is the immune immaturity of CB lymphocytes able to overcome the HLA barrier and authorize HLA-mismatched transplants? Is it possible to establish CB banks for unrelated and related transplants? What would be the criteria for collection, quality control and cryopreservation?

RETIRED: Umbilical cord blood banking: implications for perinatal care providers.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.