Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an hla-identical sibling
26 Oct 1989-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 321, Iss: 17, pp 1174-1178
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for Fanconi's anemia preoperatively on the basis of prior history and once they provide informed consent for surgery.
Abstract: The clinical manifestations of Fanconi’s anemia, an autosomal recessive disorder, include progressive pancytopenia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi’s anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi’s anemia who received cryo-preserved umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifically for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]).
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TL;DR: Hematopoietic stem-cell transplantation was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and modulating the immune response had to be solved before the procedure could be used clinically as mentioned in this paper.
Abstract: Hematopoietic stem-cell transplantation, which is used to treat both malignant and nonmalignant conditions, was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and modulating the immune response had to be solved before the procedure could be used clinically. This review summarizes background information about hematopoietic stem-cell transplantation and discusses the current role of the procedure.
2,180 citations
TL;DR: Placental blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution and is associated with the severity of GVHD, type of leukemia, and stage of the disease.
Abstract: Background A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We evaluated this experience. Methods Placental blood was stored under liquid nitrogen and selected for specific patients on the basis of HLA type and leukocyte content. Patients were prepared for the transplantation of allogeneic hematopoietic cells in the placental blood and received prophylaxis against graft-versus-host disease (GVHD) according to routine procedures at each center. Results Outcomes at 100 days after transplantation were known for all 562 patients, and outcomes at 1 year for 94 percent of eligible recipients. The cumulative rates of engraftment among the recipients, according to actuarial analysis, were 81 percent by day 42 for neutrophils (median time to engraftment, 28 days) and 85 percent by day 180 for platelets (median, day 90). The speed of myeloid engraftment was as...
1,353 citations
TL;DR: Surprisingly, these cells were also able to differentiate into neuroglial- and hepatocyte-like cells under appropriate induction conditions and, thus, they may be more than mesenchymal stem cells as evidenced by their ability to differentiation into cell types of all 3 germ layers.
1,320 citations
TL;DR: A registry containing information on the outcome of cord-blood transplantation from 1988 to 1996 was established, and younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors.
Abstract: Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...
1,245 citations
TL;DR: Cord blood from an unrelated donor is an alternative source of hematopoietic stem cells for adults with acute leukemia who lack an HLA-matched bone marrow donor.
Abstract: results Recipients of cord blood were younger than recipients of bone marrow (median, 24.5 vs. 32 years of age; P<0.001), weighed less (median, 58 vs. 68 kg; P<0.001), and had more advanced disease at the time of transplantation (52 percent vs. 33 percent, P<0.001). All marrow transplants were HLA matched, whereas 94 percent of cord-blood grafts were HLA mismatched (P<0.001). The median number of nucleated cells that were infused was 0.23¬10 8 per kilogram of the recipient’s body weight for cord blood and 2.9¬10 8 per kilogram for bone marrow (P<0.001). Multivariate analysis showed lower risks of grade II, III, or IV acute graft-versus-host disease (GVHD) after cord-blood transplantation (relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87; P=0.01), but neutrophil recovery was significantly delayed (relative risk, 0.49; 95 percent confidence interval, 0.41 to 0.58; P<0.001). The incidence of chronic GVHD, transplantation-related mortality, relapse rate, and leukemia-free survival were not significantly different in the two groups. conclusions Cord blood from an unrelated donor is an alternative source of hematopoietic stem cells for adults with acute leukemia who lack an HLA-matched bone marrow donor.
1,087 citations
References
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TL;DR: All with an interest in tumours will find something to stimulate them in this book but even these items are to some extent outweighed by the insight given into the thoughts and policies of this fascinating country.
Abstract: It is one of the anomalies of political history that the international medical world has, until recently, been better informed about cancer patterns and cancer research in tropical Africa than in China. Following the overthrow of the 'Gang of Four' a team of US oncologists travelled widely through that vast country, and this book is a record of what they saw. It gives a detailed account of cancer epidemiology, research, diagnosis, and treatment, and of the medico-political background. Most people are familiar with what seems to western eyes to be a curious combination of traditional medicine (acupuncture and herbal therapy) and of high technology, particularly in the field of surgery. Fewer may be aware of the interesting epidemiological studies which have shown high incidence areas of oesophageal, nasopharyngeal, and hepatic carcinoma; of the geographical association of some of these tumours with a high incidence in domestic animals; or of the diagnosis of precancerous oesophageal lesions by cytology obtained by barefoot doctors. All with an interest in tumours will find something to stimulate them in this book but even these items are to some extent outweighed by the insight given into the thoughts and policies of this fascinating country.
1,210 citations
TL;DR: It was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy.
Abstract: The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3 The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution
1,192 citations
"Hematopoietic reconstitution in a p..." refers background or methods or result in this paper
...* The preparation for the assays has been described elsewhere [12]....
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...This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12])....
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...Immediately after the birth of the patient‘s sister, blood was obtained from her umbilical cord and the placenta as described elsewhere [12] and transported at ambient temperature by overnight express service to a laboratory for cellular analysis, cryopreservation, and storage (Indiana University School of Medicine)....
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...Bone marrow and, under certain circumstances, the blood of adults (see references cited by Broxmeyer et al [12]) and the liver of fe- tuses [17] have been used in the transplantation of hematopoietic cells....
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...These values were within the range associated with successful transplantation of HLA–matched allogeneic bone marrow [12]....
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TL;DR: Experiments in which viable FA fibroblasts were exposed to a direct-acting mutagen or carcinogen for a period of 6 d, ensuring chronic exposure of the cells during one or more cell cycles, until increased cell density inhibited further cell division.
Abstract: INDIVIDUALS with certain genetic syndromes associated with chromosome damage show markedly increased incidence of cancer1. In one such syndrome, Fanconi's anaemia (FA), chromosomal breakage and rearrangement has been found in lymphocytes and fibroblasts2,3 years before the development of malignant tumours. There is some evidence that cells from FA patients are especially sensitive to oncogenic agents. FA fibroblasts are abnormally susceptible to SV40 transformation4, and lymphocytes from patients show increased chromosome aberrations after exposure to ionising radiation5, or to alkylating agents6,7. In these reports, however, evaluation was based on cells which entered metaphase during brief and possibly toxic exposures to chemicals. We report here experiments in which FA fibroblasts were exposed to a direct-acting mutagen or carcinogen for a period of 6 d, ensuring chronic exposure of the cells during one or more cell cycles, until increased cell density inhibited further cell division. After subculture we could then assay chromosome damage in cells capable of entering a new cycle of cell division after removal from the chemical. We found that viable FA fibroblasts showed increases in chromosome aberrations after exposure to the mutagen or carcinogen at concentrations that had no effect in other cell strains tested. Since fibroblasts can be maintained in serial passage, their use in this protocol makes it possible to examine residual and possibly lasting effects of the treatment.
339 citations
"Hematopoietic reconstitution in a p..." refers background or methods in this paper
...Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi’s anemia, both prenatally and postnatally [3-6]....
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...Chromosome-breakage studies were performed as described elsewhere [4]....
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Journal Article•
312 citations
TL;DR: It is concluded that hypersensitivity to the clastogenic effect of DEB is a useful discriminator for FA and a simplified scoring method for classifying patients on the basis of eight clinical manifestations that are the best predictors for FA is presented.
311 citations