REVIEWMilestones in umbilical cord blood transplantation
Introduction
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.1 These advantages were first recognized in CBT using related donors; secondarily, cord blood banks (CBB) established criteria for standardization of cord blood collection, banking, processing, and cryopreservation for unrelated donor transplants in patients with various hematological malignant and non malignant diseases.2 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 (CBB) and transplant centers has been established for a common inventory, 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.
Section snippets
Pre clinical steps
The concept of using cord blood was developed in the late 1970s, however the pivotal work of H.E. Broxmeyer moved UCB from the laboratory to clinical practice. H.E. Boyse provided the proof of concept studies in mice while H.E. Broxmeyer systematically evaluated the hematopoietic potential of human UCB in vitro and developed practical and efficient methods for large volume collection and storage of UCB. It was postulated at that time that UCB collected at birth might contain enough
From the first umbilical cord blood transplant to the development of umbilical cord blood banks
The first UCBT was performed in 1988 in a patient with FA.1 This patient had a healthy HLA identical sibling shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype and to be HLA identical to the patient. Her cord blood was collected at birth, cryopreserved and used after thawing for transplantation. The patient was conditioned by a procedure developed specifically for the treatment of FA patients who are extremely sensitive to the administration of alkylating
Milestones in the development of CBT
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Optimization of UCB collection and storage.[2], [3], [14]
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First HLA identical sibling cord blood transplant in a patient with Fanconi anemia.1
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Development of CBB for related and unrelated transplants (Paris, Dusseldorf, New York, Milan).15
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First unrelated mismatched cord blood transplant in children.16
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First unrelated cord blood transplant in adult.17
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Creation of the Eurocord Netcord network.18
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Description of criteria of donor choice based on number of cells and possibility to use mismatched cord
International organization of cord blood transplant
Since the first UCBT, more than 20,000 CBT have been reported worldwide and more than 600,000 cord blood units have been stored in more than 100 cord blood banks (www.bmdw.org) (www.nmdp.org).
The main practical advantages of using cord blood as an alternative source of stem cells are the relative ease of procurement, the absence of risk for mothers and donors, the reduced likelihood of transmitting infections, particularly CMV, and the ability to store fully tested and HLA typed transplants in
Clinical experience with related and unrelated umbilical cord blood transplantation
A survey of the International Bone Marrow Transplant registry (CIBMTR) estimates that after 1998, 20% of stem cell transplants performed in young patients (< 20-year old) are cord blood transplants (IBMTR Newsletter). In Japan, nowadays approximately 50% of hematopoietic stem cell transplant (HSCT) from unrelated donors are being performed with umbilical cord blood cells.
First published large series of patients
In 1997, Eurocord published results of cord blood transplants from related and unrelated donors.18 This study included 143 patients transplanted from 1988 to 1996 in 45 transplant centers. Among 78 recipients of a related cord blood transplants, the Kaplan Mayer (KM) estimate of survival was 63%. Graft versus host disease (GVHD) was low at 9%. Favorable factor for engraftment was associated with lower age and higher number of nucleated cells. Among the 60 recipients who received a mismatched
Criteria of donor choice
The other pivotal study was to determine the criteria of choice of the cord blood units. In 2004, we analyzed 550 patients with hematological malignancies who received an UCBT from Eurocord. Neutrophil and platelet recovery were associated with the number of HLA mismatched, the number of total nucleated cells (NC) collected and infused and the use of G-CSF after transplant. Coexistence of HLA class I and II disparities and high CD34+ cell dose in the graft were associated with GVH III–IV but
Comparisons with other sources of stem cells
In children, with malignant diseases, two studies compared the outcome of unrelated UCBT and BMT. Eurocord published a study comparing the outcome of matched unrelated BMT (HLA 6 out of 6) either unmanipulated or T-depleted to mismatched UCBT. Results showed that after UCBT, engraftment was delayed, GVHD was reduced similarly to T-cell depleted BMT; relapse was the same as well as leukemia free survival.28 Eapen et al. for the CIBMTR and the NYCBB compared outcomes of 503 children with acute
Conflict of interest statement
No conflicts of interest to declare.
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2018, Hematology/Oncology Clinics of North AmericaCitation Excerpt :The 5-year OS and TFS were 88.3% and 73.9%, respectively, such good outcomes being ascribed to the high cell dose infused. As the risk of graft failure and delayed hematopoietic recovery represent major obstacles to the success of unrelated UCBT, current recommendations for UCBT in nonmalignant disorders suggest using units containing at least 3.5x107 TNC/kg recipient body weight before cryopreservation, and having less than 2 HLA disparities.37 Strategies aimed at overcoming the cell dose limitation include cotransplantation of multiple units,38 cotransplantation of UCB and either T-cell depleted (TCD) HLA-haploidentical CD34 + cells or mesenchymal stromal cells,39,40 direct intrabone injection of UCB,41 ex vivo expansion of UCB-derived stem and progenitor cells,42–46 or pre-modulation of the unit to enhance the homing to the BM niche of the UCB-derived HSC.47,48
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