Pathway to a cure. Common vision, teamwork achieve successful blood stem cell transplant.
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Adult↗
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Results for “National Marrow Donor Program”
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Sibling donor cord blood banking for children with sickle cell disease.
Although hematopoietic stem cell transplantation has curative potential for selected patients with sickle cell disease (SCD), most patients who are eligible for transplantation do not have a suitable donor. Cord blood (CB) from a sibling could provide an alternative stem cell source that, while not as well established as marrow, may offer certain advantages for selected families. These potential advantages include low risk to the infant donor, the possibility that mismatched CB units from sibling donors may be acceptable for transplantation, prompt availability of a stored CB unit for transplant, and decreased risk of clinically significant graft-versus-host disease. When families with SCD (or other transplant-treatable condition) conceive a sibling, no comprehensive research resource exists to assist the family in collecting the new infant's CB. With support from the National Heart Lung and Blood Institute, we are developing a noncommercial research-based CB Banking Program specifically for medically indicated sibling donations. In preliminary experience, we have collected CB from 52 SCD families across 19 states. Of these, 2 CB units have thus far been used for transplantation and 9 others are HLA-identical. We conclude that a CB bank focusing on sibling-donations may be feasible, but further study is required to determine whether such a bank can collect CB units of sufficient quantity and quality to support controlled trials of sibling CB transplantation. Families with a specific medical need, such as those already caring for a child with SCD, should consider collecting sibling CB as part of comprehensive care if the opportunity becomes available.
Anemia, Sickle Cell↗
Effectiveness of an organ-sharing program in providing zero HLA-A,B,DR mismatched kidneys for transplantation in Taiwan.
PURPOSE: This study evaluated the effects of organ sharing on the allocation of kidneys from cadaveric donors to uremic patients from National Cheng Kung University Hospital (CKUH) and National Taiwan University Hospital (NTUH) who were waiting for kidney transplantation. METHODS: Standard complement-dependent microcytotoxicity assays were used. Human leukocyte antigen (HLA)-A,B,C typing was performed on nylon-wool-enriched T lymphocytes. HLA-DR typing was performed on either nylon-wool-separated B cells or Dynabeads. Isolation of class II-positive cells was performed with commercial typing trays. RESULTS: Organs were allocated from a total of 88 cadaveric donors to 320 patients treated at CKUH and 179 patients treated at NTUH. Cadaveric kidneys could be allocated with an A,B,DR mismatch to 6.9% of CKUH patients and to 4.7% of NTUH patients. When CKUH and NTUH patients were pooled, the total number of kidneys that could be allocated with 0-A,B,DR mismatch increased to 13.3% (p < 0.004). However, when allocation was assessed using 10,000 potential bone marrow donors instead of the 88 cadaveric donors, kidneys could have been allocated with 0-A,B,DR mismatch to 12% (p = 0.64) of patients. No significant benefit was found when allocation estimates from the 10,000 potential bone marrow donors were compared with those for the 88 cadaveric donors. Use of epitope matching resulted in a 0-A,B cross-reactive epitope group, and a 0-DR mismatch allocation rate of 36.4% in CKUH patients and 31.8% in NTUH patients. This rate increased to 54.6% (p < 0.001) when the patients from these hospitals were pooled. CONCLUSION: The results of this study demonstrate that the pooling of patients among regional transplant centers in Taiwan can significantly enhance the benefits of an organ donation program through better HLA matching.
HLA-A Antigens↗
Pediatric oncology and hematology in Manchester, England.
The Manchester pediatric oncology unit is the third largest unit in the United Kingdom, with approximately 120 new referred cases per annum (10% of the U.K. total). Research activities include a gene therapy program, peripheral blood stem cell studies, the genetic epidemiology of childhood cancer, late-effects research (growth, body composition, pulmonary, quality of life), psychosocial studies, and clinical trial organization. Both the clinical oncology service and research activities involve close team coordination and collaboration with scientists both within and outside Manchester. A comprehensive pediatric hematology service is provided. The unit contains the second largest children's hemophilia service in the United Kingdom, serving 200 patients with congenital blood disorders. Twenty-five bone marrow transplants are performed each year (allogeneic, unrelated donor, autologous, and peripheral stem cell) for malignant and nonmalignant disorders. These activities are closely related to local, national, and international research groups.
Child↗
Current status of renal transplantation in the Kingdom of Saudi Arabia.
The reported annual incidence of end-stage renal disease in Saudi Arabia is 100 to 120 patients per million population. The first dialysis unit in Saudi Arabia was established in 1971; thereafter, rapid advances have been made in the field of renal replacement therapy. At the end of 2002, there were 144 centers offering dialysis to about 7390 patients. A National Kidney Foundation was established in 1985 to implement the cadaveric organ transplant program and to coordinate the renal care facilities. This center was renamed Saudi Center for Organ Transplantation (SCOT) in 1993 to encompass transplantation of organs other than the kidney. An impetus was achieved in 1982 with the approval by Islamic scholars of the concept of brain-death and organ transplantation. From 1979, when the first renal transplant was performed, until the end of 2002, more than 3810 renal transplants have been performed in 13 transplant centers in Saudi Arabia, in addition to 260 liver, 95 heart, 280 heart valve, 510 cornea, 4 pancreas, 8 lung, and 1000 bone marrow transplants. The survival of patients and (grafts) in those who received living related renal transplants was 98.4(96.9), 96.7(96.7), and 96.7(92.2) at 1, 3, and 5 years, respectively. Moreover, the survival of patients and grafts among those who received cadaveric donor organs was 96.2(96.2), 93(92.1), and 93(87.2), at 1, 3, and 5 years, respectively. In conclusion, there has been increased renal transplantation in Saudi Arabia and there is even more room to increase the frequency of these transplants to decrease the expanding gap between supply and demand through increasing the efforts for organ donation from living and cadaveric donors.
Humans↗
[Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting].
Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease.
Adolescent↗
Validation of DNA-based HLA-A and HLA-B testing of volunteers for a bone marrow registry through parallel testing with serology.
A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and PCR-based typing. The HLA assignments included all of the known serological equivalents. The majority of the individuals (99.9%) were from U.S. minority population groups. The serologic typing was performed between 1993 and 1997 at the time of recruitment for the National Bone Marrow Program (NMDP) registry. The polymerase chain reaction (PCR)-based typing was carried out in two phases. In phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without knowledge of the serologic assignments. Discrepancies were identified between the serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a potential explanation was assigned each discrepant serology/DNA pair. In phase II, a random sampling scheme was used to select a statistically significant number of individuals for repeat DNA typing from each of these categories. The categories included antigens missed by serology, nonexpressed (null) alleles, PCR amplification failures, misassignment of antigens and nomenclature issues. Only a single individual was found to carry a null allele. DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than 97% at both HLA-A and -B validating this methodology for registry typing.
Bone Marrow Examination↗
[Allogenic bone marrow transplant in Italy].
On July 7h, 1988 all Italian groups practicing allogeneic bone marrow transplantation (AlloBMT) convened with the objectives of performing an analysis of their clinical material and designing some cooperative retrospective and prospective studies. It was felt that, although the great majority of the Institutions performing AlloBMT contribute data to the International Bone Marrow Transplant Registry (IBMTR) and to the European Group for Bone Marrow Transplantation (EBMT), it might still be of interest to pursue specific regional studies, establish a National Registry, and program workshops and educational meetings. The Italian Group for Bone Marrow Transplantation (GITMO) was accordingly founded. It has been determined that by December 31st, 1988, 1390 AlloBMTs have been performed in Italy by 19 Centres. Fourteen have been involved in BMT for adults and children, and 5 exclusively for children. The chief indication for AlloBMT in this clinical material was chronic myelogenous leukaemia, followed by homozygous beta thalassaemia and by the acute leukaemias; severe aplastic anaemia, malignant lymphomas and multiple myeloma have also been important indications. Overall crude survival was 58.3%; this was reduced to 50% for patients over 20, while it reached 62.5% for those under 20. Other studies are in preparation, and a similar survey for Auto BMT has been presented at the GITMO Meeting of June 28, 1989, which is currently in press.
Bone Marrow Transplantation↗
[Umbilical cord blood as a source of stem cells].
Umbilical cord blood (UCB) is a source of the rare but precious primitive hematopoietic stem cells (HSC) and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders treated with myeloablative therapy. UCB cells possess an enhanced capacity for progenitor cell proliferation and self-renewal in vitro. UCB is usually discarded, and it exists in almost limitless supply. The blood remaining in the delivered placenta is safely and easily collected and stored. The predominant collection procedure currently practiced involves a relatively simple venipuncture, followed by gravity drainage into a standard sterile anti-coagulant-filled blood bag, using a closed system, similar to the one utilized on whole blood collection. After aliquots have been removed for routine testing, the units are cryopreserved and stored in liquid nitrogen. UCB banks are being established throughout the world and UCB units are collected for allogeneic unrelated and related HSC transplantation. In unrelated cord blood banks donated UCB units are collected and stored for allogeneic use in patients who do not have an identified HLA matched relative. UCB banks report available units to national and international donor registries. The second model of UCB banking is referred to as family banking, where UCB is stored for the benefit of the donor or their family members. After more than one decade of clinical experience, it is currently accepted that UCB transplants, related and unrelated, are equivalent to or might compare favorably with bone marrow (BM) transplants, especially in children. Initial studies of long-term survival in children with both malignant and non-malignant hematologic disorders, who were transplanted with UCB from a sibling donor, demonstrated comparable or superior survival to children who received BM transplantation. One factor that limits the use of UCB transplantation in adult patients is the relatively limited number of HSC that may be harvested from umbilical cord, resulting in a slower time to engraftment and higher transplant related mortality, mainly due to the long aplasia period after transplantation and susceptibility to viral and fungal infections. Despite prolonged periods of aplasia, the apparent reduction in the incidence and severity of graft versus host disease (GVHD) may in turn underline comparable rates of survival in some series comparing UCB to adult-donor sources. The "naive" nature of UCB lymphocytes may explain the lower incidence and severity of GVHD encountered in UCB transplantation compared to the allogeneic BM transplant setting. UCB transplantation does not seem to be associated with increased rates of disease relapse. The available data suggest that nucleated cell dose in UK unit should be the primary criterion for donor selection. In 1991, the UCB transplantation program was established at the Zagreb University Hospital Center for related transplants, and until now 4 UCB transplantations have been performed successfully. In order to speed up the engraftment rate, several strategies such as multiple UCB transplants and ex vivo expansion of HSC have been assayed. The current strategies are focused on the development of much more efficient technologies for ex vivo production of progenitor cells, but whether expansion will speed engraftment and improve outcome after UCB remains to be determined. UCB is known to contain extremely immature stem cells. Consequently, such pluripotent or, perhaps, multipotent stem cells have been proposed as elements suitable for cellular therapy and regenerative medicine. Up to date there are no conclusive data regarding these possibilities but preliminary in vitro and animal studies in the field of tissue regeneration suggest some degree of plasticity and/or transdifferentiation. UCB cells are showing their unique qualities and potential, and consequently UCB banks might dramatically increase the scope of their clinical application.
Blood Banks↗
Status of liver and gastrointestinal transplantation at the University of Miami.
The liver transplant program at the University of Miami, established in 1987, was rejuvenated in June 1994 with the addition of new staff and expanded to include all organs of the gastrointestinal tract. Since its inception, 630 patients have been transplanted in the program. During the past 2 years we performed 349 transplants in 318 patients (livers n = 323 in 298 patients, liver + kidneys n = 13, liver + islet n = 10, liver + kidney + islets n = 1, liver + heart n = 10, liver + lung n = 1). These included 4 split-liver, 3 living-related, multiple reduced-sized and one "Domino" liver transplant. We have an active pediatric program and 10% of our transplanted patients are pediatric. Our overall patient and graft survival rates were 81% and 78%, respectively. The intestinal transplant program was launched in August 1994. To date we have performed 22 intestinal transplants, in 9 adults and 13 children. These transplants included 4 isolated intestinal, 11 combined liver-intestinal and 7 multivisceral transplants. Overall patient and graft survival rates were 55% and 50%, respectively. During the past 2 years several studies involving immunosuppressive agents were carried out: 1)Mycophenolate Mofetil (MMF) was used as induction therapy and as rescue therapy in patients with steroid-resistant rejection. Tacrolimus toxicity, and chronic rejection; 2) Neoral was compared with Tacrolimus in patients with Hepatitis C; and 3) MMF was added as triple therapy for the intestinal transplants. We used alpha interferon-2b (alpha-IFN) in hepatitis C positive patients in the early posttransplant period and found that it appears to be a safe drug. There was no increase in rejection in patients receiving alpha-IFN, and patient and graft survival were the same as in our overall patient population. A combination a-IFN with Ribavirin will be undertaken in the near future. The use of Lamivudine in hepatitis B patients was shown to be effective in preventing and treating recurrence of hepatitis B posttransplant. Unmodified donor bone marrow cells (DBMC) were isolated from the vertebral bodies of the same cadaveric liver donors. Donor bone marrow dose, number of cells and/or number (or timing) of infusions were investigated to determine which variables affected the ability of DBMC to engraft in the liver recipient. The long-term benefit of DBMC needs further follow-up. Although, our patient and graft survival for liver transplant recipients is comparable to other large centers nationally and internationally, we still have some challenges to overcome. These include: 1) control and prevention of recurrent HCV, 2) improved treatment for hepatocellular cancer pre- and posttransplant, and 3) treatment and prevention of chronic rejection. Intestinal transplantation remains an even greater challenge. Diagnostic tests to determine intestinal function need further development and although MMF has shown some promise in this field, newer immunosuppressive medications need to be investigated to prevent rejection and avoid over immunosuppression.
Adult↗