Frequency analysis of cytotoxic T lymphocyte precursors in search for donors in bone marrow transplantation

International Nuclear Information System (INIS)

Cukrova, V.; Dolezalova, L.; Loudova, M.; Matejkova, E.; Korinkova, P.; Lukasova, M.; Stary, J.

1995-01-01

The usefulness of cytotoxic T lymphocytes (CTLp) frequency analysis in the search for donors in bone marrow transplantation was studied. The frequency of anti-recipient CTLp was approached by limiting dilution assay in HLA matched unrelated, HLA partially matched related and HLA genotypically identical donors. The majority of patients examined were affected with different hematological malignancies. Allo-reactive CTLp recognizing non-HLA gene products were not detected in pre-transplant examination of two pairs of HLA identical siblings. However, an increase incidence of allo-specific CTLp was identified in HLA matched mixed lymphocyte culture (MLC) negative unrelated pairs. Thus, CTLp assay allowed to the residual Class I incompatibilities that remained hidden in standard serotyping. In two matched unrelated pairs with high pretranslant CTLp frequency the severe acute graft-versus-host diseases developed after bone marrow transplantation. Examination of other relatives in patients lacking an HLA identical sibling showed the importance of Class I incompatibility for CTLp generation as well. The lack of correlation between CTLp frequency and HLA-D disparity could suggest that Class II antigens do not participate in CTLp induction. With one exception we had good correlation between MLC and DNA analysis of Class II antigens demonstrating that MLC gives interpretable results even in unrelated pairs. Our results demonstrate the significance of CTLp frequency assay in detection of residual Class I incompatibilities in matched unrelated pairs and in assessment of Class I compatibility in related pairs. For that it should be used in the final selection of bone marrow transplantation donors. (author)

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

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Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory

Quality of harvest and role of cell dose in unrelated bone marrow transplantation: an Italian Bone Marrow Donor Registry-Gruppo Italiano Trapianto di Midollo Osseo Study.

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Fagioli, Franca; Quarello, Paola; Pollichieni, Simona; Lamparelli, Teresa; Berger, Massimo; Benedetti, Fabio; Barat, Veronica; Marciano, Renato; Rambaldi, Alessandro; Bacigalupo, Andrea; Sacchi, Nicoletta

2014-01-01

In this study, we investigated the factors affecting cell dose harvest and the role of cell dose on outcome. We analysed data from a cohort of 703 patients who underwent unrelated bone marrow transplantation facilitated by IBMDR in GITMO centers between 2002 and 2008. The median-infused cell doses is 3.7 × 10(8)/kg, the correlation between the nucleated cells requested from transplant centers and those harvested by collection centers was adequate. A harvested/requested cells ratio lower than 0.5 was observed only in 3% of harvests. A volume of harvested marrow higher than the median value of 1270 ml was related to a significant lower infused cell dose (χ(2): 44.4; P < 0.001). No patient- or donor-related variables significantly influenced the cell dose except for the recipient younger age (χ(2): 95.7; P < 0.001) and non-malignant diseases (χ(2): 33.8; P < 0.001). The cell dose resulted an independent predictor factor for a better outcome in patients affected by non-malignant disease (P = 0.05) while early disease malignant patients receiving a lower cell dose showed a higher risk of relapse (P = 0.05).

Selection of unrelated donors for bone marrow transplantation studied in rhesus monkeys

International Nuclear Information System (INIS)

Wagemaker, G.; Bekkum, D.W. van

Graft versus Host disease (GvHD) remains to be a severe limitation to a more general application of bone marrow transplantation. Clinically acceptable results are restricted to those potential recipients for which a major histocompatibility complex (MHC) identical sibling donor is available. At an average family size of 2 to 3 siblings, the frequency of such donors is not more than approximately 30%. This pre-clinical study in rhesus monkeys is directed at the selection of donors for recipients which lack an MHC identical sibling. (Auth.)

The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

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Eid K.A.B.

2003-01-01

Full Text Available The feasibility of allogeneic bone marrow transplantation (alloBMT in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years, 684 (60.1% were males and 454 (39.9% were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8% candidates had full match donors; 352/1138 (30.8% were eligible for alloBMT. Only 235 of 352 (66.7% were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%; monthly family income ranged from US$60 (7% to more than US$400 (36%. Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.

Protecting the interests of the child bone marrow donor.

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Terry, Louise M; Campbell, Anne

2004-01-01

At a time when designer babies have been created to act as cord blood donors to sick siblings, ethical debate has focused predominantly on the extent to which it is acceptable to create one human being to assist another. However, children are frequently used this way, by their families and doctors who extract their bone marrow, to try to save the life of another, usually a sibling. With any life-threatening illness, there is the possibility that the urgency of the sick sibling's need means that the short-term welfare of the donor child receives less attention than it should by parents and doctors. This article suggests ways to protect the interests of such children and empower them within the decision-making process and concludes that the drive to save life must be tempered by recognition of the intrinsic worth of donor children and their rights not to be exploited.

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

International Nuclear Information System (INIS)

Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

1990-01-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

Energy Technology Data Exchange (ETDEWEB)

Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. (Columbia Univ. College of Physicians and Surgeons, New York, NY (USA))

1990-05-01

Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

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Colnot, C.; Huang, S.; Helms, J.

2006-01-01

The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis

Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

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Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

1988-01-01

When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

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Yasumizu, R.; Hiai, H.; Sugiura, K.

1988-01-01

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

Charting improvements in US registry HLA typing ambiguity using a typing resolution score.

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Paunić, Vanja; Gragert, Loren; Schneider, Joel; Müller, Carlheinz; Maiers, Martin

2016-07-01

Unrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score (TRS), based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations. We apply the TRS to chart improvement in HLA typing within the Be The Match Registry of the United States from the initiation of DNA-based HLA typing to the current state of high-resolution typing using next-generation sequencing technologies. In addition, we present a publicly available online tool for evaluation of any given HLA typing. This TRS objectively evaluates HLA typing methods and can help define standards for acceptable recruitment HLA typing. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Bone Marrow: A Prespecified Analysis from the Phase III BMT CTN Protocol 0201

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Burns, Linda J.; Logan, Brent R.; Chitphakdithai, Pintip; Miller, John P.; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E.; Wingard, John R.; Anasetti, Claudio; Confer, Dennis L.

2016-01-01

We report a comparison of time to recovery, side effects, and change in blood counts from baseline to post-donation of unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase III randomized, multicenter trial (0201) in which donor/recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) from international centers (145 German and 9 Canadian). PBSC donors recovered in less time with a median time to recovery of 1 week compared to 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months post-donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time post donation compared to BM donors (HR 2.08 [95% CI 1.73–2.50], pdonor and donation in more recent years. Donors of BM were more likely to report grade 2–4 skeletal pain, body symptoms and fatigue at 1 week post donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 post-collection of BM donors) could be analyzed, no variable was significantly associated with grade 2–4 skeletal pain, including product donated (BM vs PBSC, OR 1.13 [95% CI 0.74–1.74], p=0.556). Blood counts were impacted by product donated, with mean change from baseline to post-donation being greater for white blood cells, neutrophils, mononuclear cells and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference. PMID:27013014

Survival of allografts from bone marrow donors in temporary dog radiation chimeras

International Nuclear Information System (INIS)

Vriesendorp, H.M.

Complete radiation chimeras accept indefinitely a skin or a kidney graft from the bone marrow (BM) donor. The advantages of this method of inducing graft acceptance are that it does not require the use of toxic post-operative immunosuppressive agents and that the immune reactivity against antigens other than the ones carried by the BM donor remains intact. The disadvantages of this approach are that supralethal total body irradiation (TBI) causes toxicity and that allogeneic BM cells can cause lethal Graft versus Host reactions. Attempts were made to diminish the significance of these disadvantages by using lower dose TBI and giving fewer BM cells. It is shown that, in dogs, 7.5 Gy TBI followed by 4 X 10 8 BM cells.kg -1 body weight of a DLA identical sibling leads to the development of complete radiation chimeras. The exclusive presence of donor type haemopoiesis can be demonstrated by determinations of 'informative' genetic markers, i.e., markers that show different genotypes in donor and recipient. (Auth.)

Percepção da comunidade nipo-brasileira residente em Curitiba sobre o cadastro de medula óssea The perception of the bone marrow registry of Brazilian Japanese descendants living in the city of Curitiba, Brazil

Directory of Open Access Journals (Sweden)

Alexandra M. Watanabe

2010-01-01

. However, in the general population there are few compatible donors for patients. Fortunately, there is a better chance of finding compatible donors in the same ethnical group as the patient. In the city of Curitiba, the state of Paraná, few Japanese descendants are registered as bone marrow donors in the State Blood Center (Hemepar. The purpose of this study was to investigate the perception of the Japanese descendants of the Bone Marrow Registry and in particular the possible reasons that few of these individuals are registered. Data were collected from April to May of 2008, through an interview process applied at random to 400 Japanese descendants. Results were tabulated on a Microsoft Office Excel 2003 spreadsheet and statistical analyses were performed using the Statgraphics Software, version 5.1. In spite of the good cultural background (56% and good knowledge about bone marrow (77%, Japanese descendents in particular second and third generation subjects did not join the registry not only because of the lack of information about where it is possible to be registered but also because of the lack of information about the donation process itself. It is necessary to develop strategies to provide correct information to the population in order to stimulate Japanese descendants to join the bone marrow registry. Knowledge of the characteristics of the different ethnical groups which compose the Brazilian population is an indicator that may help to increase the number of registered bone marrow donor.

Leading Efforts to Increase Organ Donation Through Professionalization of Organ Procurement Organizations and Establishment of Organ and Tissue Donor Registries.

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Vertanous, T; Czer, L S C; de Robertis, M; Kiankhooy, A; Kobashigawa, J; Esmailian, F; Trento, A

2016-01-01

The influence of new donor registrations through the California Organ and Tissue Donor Registry on the local OneLegacy Organ Procurement Organization (OPO) was examined during a 6-year period. Publicly available data from Donate Life America for California were examined for the 6 calendar years of 2009-2014. Performance data from OneLegacy for the same 6 years for organ donors and number of transplants were also examined. The donor designation rate (DDR) was defined as the rate at which new individuals joined the state donor registry as a percentage of all driver licenses and ID cards issued within a calendar year. The total donor designation (TDD) was defined as the sum of the new and existing people who were registered organ donors. Donor designation share (DDS) was the total number of designated donors as a percentage of all residents of the state who were ≥18 years old. The business practices and educational efforts of the OneLegacy OPO were examined as well. In California, from 2009 through 2014, the DDR was 25.5%-28%. When added to the existing donor registrations, the TDD and DDS increased each year from 2009 through 2014. With the current level of growth, it is projected that California will be able to reach a DDS of 50% by 2017. For the OneLegacy OPO, designated donors from the California Organ and Tissue Donor Registry made up 15% of the total donations in 2009, and 39% of the total donations in 2014, increasing by ∼5% each year since 2009. By increasing professionalization and transparency, and widening its educational and training efforts, OneLegacy was able to take advantage of an increasing percentage of donors who were designated donors and to increase the overall number of donors and organs transplanted, becoming one of the largest OPOs in the nation. This can be a model for OPOs in other donor service areas, and it may set the stage for the United States to serve as an example to the global community in the practice of organ donation. Copyright

A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

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2016-08-15

donors and cord blood units W. Bochtler1, L. Gragert2, Z. I. Patel3, J. Robinson3,4, D. Steiner5, J. A. Hofmann6, J. Pingel6, A. Baouz7, A. Melis8, J...cord blood units for individual patients is of primary importance. This challenging search process is routinely performed in a donor registry or cord...term ‘ donor ’ to refer to donors of HSCs from bone marrow or peripheral blood and cord blood units and the term ‘ donor registry’ shall include cord blood

Immunohistochemical localization of host and donor-derived cells in the regenerating thymus of radiation bone marrow chimeras

International Nuclear Information System (INIS)

Ceredig, R.; Schreyer, M.

1984-01-01

The anatomical distribution of CBA (Thy-1.2) host and AKR (Thy-1.1) donor-derived cells in the regenerating thymus of AKR → CBA radiation bone marrow chimeras was investigated. Cryostat sections of chimeric thymuses were incubated with biotin-conjugated monoclonal anti-Thy-1 antibodies specific for host and donor-derived cells and the distribution of the corresponding Thy-1 antigen revealed by the immunoperoxidase staining technique. The thymus was initially repopulated by Thy-1.2 + host-derived cells, but by 28 days following bone marrow reconstitution the few remaining host cells were found mostly in the thymus medulla. However, occasional Thy-1.2 + cells were still present in extramedullary, primarily cortical, sites. Donor-derived (Thy-1.1 + ) cells were first seen in the 11-day chimeric thymus as single cells frequently closely associated with blood vessels in medullary areas. By 17 days, the cortex contained many Thy-1.1 + cells, although occasional single positive cells were still present in the medulla. Changes in the anatomical distribution of host and donor-derived cells in the regenerating chimeric thymus appeared to correlate with changes in their Thy-1 fluorescence profile as determined by flow microfluorometry. (Auth.)

HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

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Gragert, Loren; Eapen, Mary; Williams, Eric; Freeman, John; Spellman, Stephen; Baitty, Robert; Hartzman, Robert; Rizzo, J. Douglas; Horowitz, Mary; Confer, Dennis; Maiers, Martin

2018-01-01

Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in

The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Jacobsen, N

1987-01-01

Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

Marrow transfusions into normal recipients

International Nuclear Information System (INIS)

Brecher, G.

1983-01-01

During the past several years we have explored the transfusion of bone marrow into normal nonirradiated mice. While transfused marrow proliferates readily in irradiated animals, only minimal proliferation takes place in nonirradiated recipients. It has generally been assumed that this was due to the lack of available proliferative sites in recipients with normal marrow. Last year we were able to report that the transfusion of 200 million bone marrow cells (about 2/3 of the total complement of marrow cells of a normal mouse) resulted in 20% to 25% of the recipient's marrow being replaced by donor marrow. Thus we can now study the behavior of animals that have been transfused (donor) and endogenous (recipient) marrow cells, although none of the tissues of either donor or recipient have been irradiated. With these animals we hope to investigate the nature of the peculiar phenomenon of serial exhaustion of marrow, also referred to as the limited self-replicability of stem cells

Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program.

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Pulsipher, Michael A; Chitphakdithai, Pintip; Logan, Brent R; Shaw, Bronwen E; Wingard, John R; Lazarus, Hillard M; Waller, Edmund K; Seftel, Matthew; Stroncek, David F; Lopez, Angela M; Maharaj, Dipnarine; Hematti, Peiman; O'Donnell, Paul V; Loren, Alison W; Leitman, Susan F; Anderlini, Paolo; Goldstein, Steven C; Levine, John E; Navarro, Willis H; Miller, John P; Confer, Dennis L

2013-01-03

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.

Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies.

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Garcia, Maria C; Chapman, Jeremy R; Shaw, Peter J; Gottlieb, David J; Ralph, Angelique; Craig, Jonathan C; Tong, Allison

2013-07-01

Hematopoietic stem cell (HSC) transplantation using bone marrow and peripheral blood stem cells is a lifesaving treatment for patients with leukemia or other blood disorders. However, donors face the risk of physical and psychosocial complications. We aimed to synthesize qualitative studies on the experiences and perspectives of HSC donors. We searched MEDLINE, Embase, PsycINFO, CINAHL, Google Scholar, and reference lists of relevant articles to November 13, 2012. Thematic synthesis was used to analyze the findings. Thirty studies involving 1552 donors were included. The decision to donate included themes of saving life, family loyalty, building a positive identity, religious conviction, fear of invasive procedures, and social pressure and obligation. Five themes about the donation experience were identified: mental preparedness (pervasive pain, intense disappointment over recipient death, exceeding expectations, and valuing positive recipient gains), burden of responsibility (striving to be a quality donor, unresolved guilt, and exacerbated grief), feeling neglected (medical dismissiveness and family inattention), strengthened relationships (stronger family ties, establishing blood bonds), and personal sense of achievement (satisfaction and pride, personal development, hero status, and social recognition). Although HSC donation was appreciated as an opportunity to save life, some donors felt anxious and unduly compelled to donate. HSC donors became emotionally invested and felt responsible for their recipient's outcomes and were profoundly grieved and disappointed if the transplantation was unsuccessful. To maximize donor satisfaction and mitigate the psychosocial risks for HSC donors, strategies to address the emotional challenges of anxiety, sense of coercion, guilt, and grief in donors are warranted. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Impact of selection of cord blood units from the United States and swiss registries on the cost of banking operations.

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Bart, Thomas; Boo, Michael; Balabanova, Snejana; Fischer, Yvonne; Nicoloso, Grazia; Foeken, Lydia; Oudshoorn, Machteld; Passweg, Jakob; Tichelli, Andre; Kindler, Vincent; Kurtzberg, Joanne; Price, Thomas; Regan, Donna; Shpall, Elizabeth J; Schwabe, Rudolf

2013-02-01

Over the last 2 decades, cord blood (CB) has become an important source of blood stem cells. Clinical experience has shown that CB is a viable source for blood stem cells in the field of unrelated hematopoietic blood stem cell transplantation. Studies of CB units (CBUs) stored and ordered from the US (National Marrow Donor Program (NMDP) and Swiss (Swiss Blood Stem Cells (SBSQ)) CB registries were conducted to assess whether these CBUs met the needs of transplantation patients, as evidenced by units being selected for transplantation. These data were compared to international banking and selection data (Bone Marrow Donors Worldwide (BMDW), World Marrow Donor Association (WMDA)). Further analysis was conducted on whether current CB banking practices were economically viable given the units being selected from the registries for transplant. It should be mentioned that our analysis focused on usage, deliberately omitting any information about clinical outcomes of CB transplantation. A disproportionate number of units with high total nucleated cell (TNC) counts are selected, compared to the distribution of units by TNC available. Therefore, the decision to use a low threshold for banking purposes cannot be supported by economic analysis and may limit the economic viability of future public CB banking. We suggest significantly raising the TNC level used to determine a bankable unit. A level of 125 × 10(7) TNCs, maybe even 150 × 10(7) TNCs, might be a viable banking threshold. This would improve the return on inventory investments while meeting transplantation needs based on current selection criteria.

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

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Carbonaro, Denise A; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C; Dorey, Frederick; Kellems, Rodney E; Blackburn, Michael R; Kohn, Donald B

2008-06-15

Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose-dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.

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Acharya, Kelly S; Keyhan, Sanaz; Acharya, Chaitanya R; Yeh, Jason S; Provost, Meredith P; Goldfarb, James M; Muasher, Suheil J

2016-09-01

To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age cycles from 2011 to 2012. Embryos transferred in donor IVF cycles. Percentage of compliant cycles, multiple pregnancy rate. There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation of participant recruitment methods to a rare disease online registry.

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Johnson, Kimberly J; Mueller, Nancy L; Williams, Katherine; Gutmann, David H

2014-07-01

Internet communication advances provide new opportunities to assemble individuals with rare diseases to online patient registries from wide geographic areas for research. However, there is little published information on the efficacy of different recruitment methods. Here we describe recruitment patterns and the characteristics of individuals with the self-identified autosomal dominant genetic disorder neurofibromatosis type 1 (NF1) who participated in an online patient registry during the 1-year period from 1/1/2012 to 12/31/2012. We employed four main mechanisms to alert potential participants to the registry: (1) Facebook and Google advertising, (2) government and academic websites, (3) patient advocacy groups, and (4) healthcare providers. Participants reported how they first heard about the registry through an online questionnaire. During the 1-year period, 880 individuals participated in the registry from all 50 U.S. States, the District of Columbia, Puerto Rico, and 39 countries. Facebook and Google were reported as referral sources by the highest number of participants (n=550, 72% Facebook), followed by healthcare providers (n=74), and government and academic websites (n=71). The mean participant age was 29±18 years and most participants reported White race (73%) and female sex (62%) irrespective of reported referral source. Internet advertising, especially through Facebook, resulted in efficient enrollment of large numbers of individuals with NF1. Our study demonstrates the potential utility of this approach to assemble individuals with a rare disease from across the world for research studies. © 2014 Wiley Periodicals, Inc.

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

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Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D'aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; Peffault de Latour, Regis

2016-07-01

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; Paplastic anemia. Copyright© Ferrata Storti Foundation.

Risk-Factor Profile of Living Kidney Donors: The Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry 2004-2012.

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Clayton, Philip A; Saunders, John R; McDonald, Stephen P; Allen, Richard D M; Pilmore, Helen; Saunder, Alan; Boudville, Neil; Chadban, Steven J

2016-06-01

Recent literature suggests that living kidney donation may be associated with an excess risk of end-stage kidney disease and death. Efforts to maximize access to transplantation may result in acceptance of donors who do not fit within current guidelines, potentially placing them at risk of adverse long-term outcomes. We studied the risk profile of Australian and New Zealand living kidney donors using data from the Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry over 2004 to 2012. We compared their predonation profile against national guidelines for donor acceptance. The analysis included 2,932 donors (mean age 48.8 ± 11.2 years, range 18-81), 58% female and 87% Caucasian. Forty (1%) had measured glomerular filtration rate less than 80 mL/min; 32 (1%) had proteinuria >300 mg/day; 589 (20%) were hypertensive; 495 (18%) obese; 9 (0.3%) were diabetic while a further 55 (2%) had impaired glucose tolerance; and 218 (7%) were current smokers. Overall 767 donors (26%) had at least one relative contraindication to donation and 268 (9%) had at least one absolute contraindication according to national guidelines. Divergence of current clinical practice from national guidelines has occurred. In the context of recent evidence demonstrating elevated long-term donor risk, rigorous follow-up and reporting of outcomes are now mandated to ensure safety and document any change in risk associated with such a divergence.

Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis.

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Trotter, Patrick B; Robb, Matthew; Hulme, William; Summers, Dominic M; Watson, Christopher J E; Bradley, J Andrew; Neuberger, James

2016-12-01

Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients. Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes. Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor. Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

1986-01-01

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it

Can evidence-based health policy from high-income countries be applied to lower-income countries: considering barriers and facilitators to an organ donor registry in Mumbai, India.

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Vania, Diana K; Randall, Glen E

2016-01-13

Organ transplantation has become an effective means to extend lives; however, a major obstacle is the lack of availability of cadaveric organs. India has one of the lowest cadaver organ donation rates in the world. If India could increase the donor rate, the demand for many organs could be met. Evidence from high-income countries suggests that an organ donor registry can be a valuable tool for increasing donor rates. The purpose of this study is to determine whether the implementation of an organ donor registry is a feasible and appropriate policy option to enhance cadaver organ donation rates in a lower-income country. This qualitative policy analysis employs semi-structured interviews with physicians, transplant coordinators, and representatives of organ donation advocacy groups in Mumbai. Interviews were designed to better understand current organ donation procedures and explore key informants' perceptions about Indian government health priorities and the likelihood of an organ donor registry in Mumbai. The 3-i framework (ideas, interests, and institutions) is used to examine how government decisions surrounding organ donation policies are shaped. Findings indicate that organ donation in India is a complex issue due to low public awareness, misperceptions of religious doctrines, the need for family consent, and a nation-wide focus on disease control. Key informants cite social, political, and infrastructural barriers to the implementation of an organ donor registry, including widely held myths about organ donation, competing health priorities, and limited hospital infrastructure. At present, both the central government and Maharashtra state government struggle to balance international pressures to improve overall population health with the desire to also enhance individual health. Implementing an organ donor registry in Mumbai is not a feasible or appropriate policy option in India's current political and social environment, as the barriers, identified through

Identification of a murine CD45-F4/80lo HSC-derived marrow endosteal cell associated with donor stem cell engraftment.

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Overholt, Kathleen M; Otsuru, Satoru; Olson, Timothy S; Guess, Adam J; Velazquez, Victoria M; Desbourdes, Laura; Dominici, Massimo; Horwitz, Edwin M

2017-12-26

Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ. Depletion of hematopoietic cells immediately before radioablation and hematopoietic stem cell transplantation abrogated donor HSC engraftment and was associated with strikingly flattened endosteal osteoblasts with preserved osteoblast proliferation and megakaryocyte migration. Depletion of monocytes, macrophages, or megakaryocytes (the predominant hematopoietic cell populations that survive short-term after irradiation) did not lead to an alteration of osteoblast morphology, suggesting that a hematopoietic-derived cell outside these lineages regulates osteoblast morphologic adaptation after irradiation. Using 2 lineage-tracing strategies, we identified a novel CD45 - F4/80 lo HSC-derived cell that resides among osteoblasts along the endosteal marrow surface and, at least transiently, survives radioablation. This newly identified marrow cell may be an important regulator of HSC engraftment, possibly by influencing the shape and function of endosteal osteoblasts.

Restoration of prostaglandin E2-producing splenic macrophages in 89Sr-treated mice with bone marrow from Corynebacterium parvum primed donors

International Nuclear Information System (INIS)

Shibata, Y.

1989-01-01

Administration of Corynebacterium parvum (CP), 56 mg/kg ip to CBA/J mice effected the induction of prostaglandin E2 (PGE2) producing macrophages (M phi) in the bone marrow and the spleen. Maximal release of PGE2 from M phi cultured in vitro with calcium ionophore A23187 for 2 h was reached by marrow M phi removed on 5 days after CP (450 ng/mg cell protein), and by splenic M phi 9 days after CP (400 ng/mg). Neither M phi population, however, yielded more than 6.0 ng/mg leukotriene C4. To assess ontogenic relationships mice were depleted of bone marrow and blood monocytes by iv injection of the bone-seeking isotope, 89Sr. CP was given at several points before or after bone marrow cell depletion. PGE2 production by splenic M phi harvested on day 9 after CP was profoundly impaired when CP was administered either concurrently with or 3 days after 89Sr. When CP was administered 1, 3, 5, and 7 days before 89Sr, however, the induction of PGE2-producing M phi in the spleen was unaffected. To determine whether bone marrow cells from CP-injected donors can restore PGE2-producing splenic M phi (PGSM) in 89Sr-mice, recipient mice which had and had not received CP 3 days after 89Sr were transfused with 5 x 10(6) syngeneic bone marrow cells from donor mice prepared at varying intervals after CP administration. The results clearly indicate the capacity of bone marrow cells harvested on either day 1 or 2 following CP to restore PGSM in CP-primed, but not unprimed, recipients

Granulocyte-mobilized bone marrow.

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Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

2012-11-01

In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

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Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

2018-05-01

Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.

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Bitan, Menachem; van Walraven, Suzanna M; Worel, Nina; Ball, Lynne M; Styczynski, Jan; Torrabadella, Marta; Witt, Volker; Shaw, Bronwen E; Seber, Adriana; Yabe, Hiromasa; Greinix, Hildegard T; Peters, Christina; Gluckman, Eliane; Rocha, Vanderson; Halter, Joerg; Pulsipher, Michael A

2016-01-01

Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Blood and Bone Marrow Transplant?

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... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

Constructing a Local Potential Participant Registry to Improve Alzheimer's Disease Clinical Research Recruitment.

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Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee

2018-01-01

Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.

Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

Directory of Open Access Journals (Sweden)

Irene Riezzo

2017-01-01

Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

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Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N.; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D’Souza, Anita; Fenske, Timothy S.; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A.; Prestidge, Tim D.; Savani, Bipin N.; Smith, Sonali M.; Sureda, Anna M.; Waller, Edmund K.; Jaglowski, Samantha; Herrera, Alex F.; Armand, Philippe; Salit, Rachel B.; Wagner-Johnston, Nina D.; Fuchs, Ephraim; Bolaños-Meade, Javier

2016-01-01

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. PMID:27269951

Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

International Nuclear Information System (INIS)

Ceredig, R.; McDonald, H.R.

1982-01-01

Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2 + ) thymocytes, which reaches maximum number of 10 to 20 x 10 6 cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1 + ) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10 6 ). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype

Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L.

1991-01-01

Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days

A registry analysis of damage to the deceased donor pancreas during procurement.

Science.gov (United States)

Ausania, F; Drage, M; Manas, D; Callaghan, C J

2015-11-01

Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety-six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement-related injuries. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Post-irradiation thymocyte regeneration after bone marrow transplantation

International Nuclear Information System (INIS)

Boersma, W.; Betel, I.; Daculsi, R.; Westen, G. van der

1981-01-01

Growth kinetics of the donor-type thymus cell population after transplantation of bone marrow into irradiated syngeneic recipient mice is biphasic. During the first rapid phase of regeneration, lasting until day 19 after transplantation, the rate of development of the donor cells is independent of the number of bone marrow cells inoculated. The second slow phase is observed only when low numbers of bone marrow cells (2.5 x 10 4 ) are transplanted. The decrease in the rate of development is attributed to an efflux of donor cells from the thymus because, at the same time, the first immunologically competent cells are found in spleen. After bone marrow transplantation the regeneration of thymocyte progenitor cells in the marrow is delayed when compared to regeneration of CFUs. Therefore, regenerating marrow has a greatly reduced capacity to restore the thymus cell population. One week after transplantation of 3 x 10 6 cells, 1% of normal capacity of bone marrow is found. It is concluded that the regenerating thymus cells population after bone marrow transplantation is composed of the direct progeny of precursor cells in the inoculum. (author)

Gamete donation: parents' experiences of searching for their child's donor siblings and donor.

Science.gov (United States)

Freeman, T; Jadva, V; Kramer, W; Golombok, S

2009-03-01

This study investigates the new phenomenon of parents of donor offspring searching for and contacting their child's 'donor siblings' (i.e. donor offspring conceived by the same donor) and donor. Online questionnaires were completed by 791 parents (39% lone-mother, 35% lesbian-couple, 21% heterosexual-couple, 5% non-specified) recruited via the Donor Sibling Registry; a US-based international registry that facilitates contact between donor conception families who share the same donor. Data were collected on parents' reasons for searching for their child's donor siblings and/or donor, the outcome of these searches and parents' and their child's experiences of any resulting contact. Parents' principal motivation for searching for their child's donor siblings was curiosity and for their donor, enhancing their child's sense of identity. Some parents had discovered large numbers of donor siblings (maximum = 55). Most parents reported positive experiences of contacting and meeting their child's donor siblings and donor. This study highlights that having access to information about a child's donor origins is important for some parents and has potentially positive consequences. These findings have wider implications because the removal of donor anonymity in the UK and elsewhere means that increasing numbers of donor offspring are likely to seek contact with their donor relations in the future.

Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

Energy Technology Data Exchange (ETDEWEB)

Ceredig, R.; McDonald, H.R.

1982-02-01

Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2/sup +/) thymocytes, which reaches maximum number of 10 to 20 x 10/sup 6/ cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1/sup +/) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10/sup 6/). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype.

Enhanced proliferation of transfused marrow and reversal of normal growth inhibition of female marrow in male hosts 2 months after sublethal irradiation

International Nuclear Information System (INIS)

Brecher, G.; Mulcahy, K.; Tjio, J.H.; Raveche, E.

1985-01-01

It is well established that 0.5 to 1 million marrow cells suffice to rescue (though not necessarily fully restore) lethally irradiated mice, while even 40 million cells result only in minimal seeding in isogeneic, nonirradiated mice. It was originally suggested that the results imply the existence of special proliferative sites which are filled in the nonirradiated animal, but are emptied by high doses of irradiation. In 1982 the authors demonstrated the feasibility of establishing substantial numbers of donor cells in normal, non-irradiated hosts. After four daily transfusions of 50 million marrow cells, 20-40% of the host's marrow consisted of cells of donor origin. The present paper reports the marked enhancement of the proliferation of transfused marrow cells in mice exposed to sublethal doses of irradiation of 300-900 R. Two months later, when the peripheral blood counts of the irradiated animals had returned to normal, transfusion of 100 million cells resulted in donor cell percentages of 55-100% in the peripheral blood and marrow. The authors previously found that male donor cells proliferated as readily in female as in male hosts, while female donor cells proliferated to a comparable degree only in female hosts. In the present study, male animals that had been exposed to 600-900 R 2 months earlier sustained proliferation of male and female donor cells equally well

The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests.

Science.gov (United States)

Wang, Yu-Tong; Zhao, Xiang-Yu; Zhao, Xiao-Su; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Chang, Ying-Jun; Huang, Xiao-Jun

2015-12-01

The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4-CD8- T cells, and monocytes in mixture allografts were 160.57 × 10(6), 89.29 × 10(6), 56.16 × 10(6), 10.87 × 10(6), and 137.94 × 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p donor weight with CD3+ T cells (p blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts. © 2015 AABB.

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

Science.gov (United States)

Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Experiences of offspring searching for and contacting their donor siblings and donor.

Science.gov (United States)

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2010-04-01

This study investigates a new phenomenon whereby individuals conceived by donor insemination are searching for and contacting their donor and/or 'donor siblings' (i.e. donor offspring conceived by the same donor who are their genetic half siblings). On-line questionnaires were completed by members of the Donor Sibling Registry (DSR), a US-based registry that facilitates contact between donor conception families who share the same donor. Of the 165 donor offspring who completed the survey, 15% were searching for their donor siblings, 13% were searching for their donor, and 64% were searching for both. Differences were found according to family type and age of disclosure. Fewer offspring from heterosexual couple families had told their father about their search when compared with offspring from lesbian couple families who had told their co-parent. Offspring who had found out about their conception after age 18 were more likely to be searching for medical reasons, whereas those who had found out before age 18 tended to be searching out of curiosity. Some offspring had discovered large numbers of half siblings (maximum=13). The majority of offspring who had found their donor relations reported positive experiences and remained in regular contact with them. Copyright (c) 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

National Marrow Donor Program

National Research Council Canada - National Science Library

Setterholm, Michelle

2008-01-01

... a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. pa 3...

Bone marrow-derived T lymphocytes responsible for allograft rejection

International Nuclear Information System (INIS)

Senjanovic, M.; Marusic, M.

1984-01-01

Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

Role of T cells in sex differences in syngeneic bone marrow transfers

International Nuclear Information System (INIS)

Raveche, E.S.; Santoro, T.; Brecher, G.; Tjio, J.H.

1985-01-01

Transferred marrow cells will proliferate in normal mice not exposed to irradiation or any other type of stem cell depletion when five consecutive transfers of 40 million cells are given. Approximately 25% of the mitotic cells are of male donor origin observed cytogenetically in all of the female recipient spleens and marrow analyzed from two weeks to one and one-half years after transfusions. Male donor stem cells are accepted and form a stable component of the self-renewing stem cell pool. In contrast, only 5% female cells are found in male recipients. This sex difference in engraftment is not hormonal since castration of recipients does not alter the percentage of donor cells. Rigorous T depletion of female donor bone marrow, however, increases the percentage of donor engraftment to the level observed when male marrow, either whole or T depleted, is transferred to female recipients. The success of T-depleted female stem cells to seed male recipients is observed in both C57BL/6 and CBA/J. In addition, recipient nude BALB/c males, which lack a thymus, fail to accept whole bone marrow from BALB/c females. However, male bone marrow cells seed BALB/c nude females. These studies demonstrate that the poor engraftment of female cells in transfused male recipients is abrogated by the removal of T cells from the donor female marrow

Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry.

Science.gov (United States)

Saito, Takuro; Gotoh, Mitsukazu; Satomi, Susumu; Uemoto, Shinji; Kenmochi, Takashi; Itoh, Toshinori; Kuroda, Yoshikazu; Yasunami, Youichi; Matsumoto, Shnichi; Teraoka, Satoshi

2010-10-15

This report summarizes outcomes of islet transplantation employing donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan Islet Transplantation Registry. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus, including two patients who had prior kidney transplantation. All but one donor (64/65) was DCD at the time of harvesting. Factors influencing criteria for islet release included duration of low blood pressure of the donor, cold ischemic time, and usage of Kyoto solution for preservation. Multivariate analysis selected usage of Kyoto solution as most important. Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survival defined as C-peptide level more than or equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years, respectively, whereas corresponding graft survival after multiple transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients remained free of severe hypoglycemia while three achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients. Islet transplantation employing DCD can ameliorate severe hypoglycemic episodes, significantly improve HbA1c levels, sustain significant levels of C-peptide, and achieve insulin independence after multiple transplantations. Thus, DCD can be an important resource for islet transplantation if used under strict releasing criteria and in multiple transplantations, particularly in countries where heart-beating donors are not readily available.

H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

International Nuclear Information System (INIS)

Noguchi, M.; Onoe, K.; Ogasawara, M.; Iwabuchi, K.; Geng, L.; Ogasawara, K.; Good, R.A.; Morikawa, K.

1985-01-01

To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

Hepatocyte growth factor is constitutively produced by donor-derived bone marrow cells and promotes regeneration of pancreatic β-cells

International Nuclear Information System (INIS)

Izumida, Yoshihiko; Aoki, Takeshi; Yasuda, Daisuke; Koizumi, Tomotake; Suganuma, Chisaki; Saito, Koji; Murai, Noriyuki; Shimizu, Yoshinori; Hayashi, Ken; Odaira, Masanori; Kusano, Tomokazu; Kushima, Miki; Kusano, Mitsuo

2005-01-01

Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic β-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of β-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value. The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats

The establishment of a bank of stored clinical bone marrow stromal cell products

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Sabatino Marianna

2012-02-01

Full Text Available Abstract Background Bone marrow stromal cells (BMSCs are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. Methods The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. Results Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. Conclusions The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria.

Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone Marrow Transplantation.

Science.gov (United States)

Imus, Philip H; Blackford, Amanda L; Bettinotti, Maria; Iglehart, Brian; Dietrich, August; Tucker, Noah; Symons, Heather; Cooke, Kenneth R; Luznik, Leo; Fuchs, Ephraim J; Brodsky, Robert A; Matsui, William H; Huff, Carol Ann; Gladstone, Douglas; Ambinder, Richard F; Borrello, Ivan M; Swinnen, Lode J; Jones, Richard J; Bolaños-Meade, Javier

2017-11-01

Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1

Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMTCTN 0201.

Science.gov (United States)

Waller, Edmund K; Logan, Brent R; Harris, Wayne A C; Devine, Steven M; Porter, David L; Mineishi, Shin; McCarty, John M; Gonzalez, Corina E; Spitzer, Thomas R; Krijanovski, Oleg I; Linenberger, Michael L; Woolfrey, Ann; Howard, Alan; Wu, Juan; Confer, Dennis L; Anasetti, Claudio

2014-08-01

To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8(+) T cells (CD8Tns), or naïve CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. © 2014 by American Society of Clinical Oncology.

Transfer of immunity by transfer of bone marrow cells: T-cell dependency

International Nuclear Information System (INIS)

Marusic, M.

1978-01-01

Thymectomized, lethally irradiated mice reconstituted with normal bone marrow cells succumbed when challenged ip with rat Yoshida ascites sarcoma (YAS) cells 40 days after irradiation and reconstitution. In contrast, thymectomized irradiated mice reconstituted with bone marrow cells from YAS-immune donors rejected the subsequent tumor challenge. Pretreatment of the bone marrow cells from immune donors with anti-Thy 1.2 antiserum and complement completely abolished the transfer of anti-YAS resistance. Bone marrow cells from donors thymectomized 2 months before immunization enabled almost all recipients to reject YAS, but bone marrow cells from donors thymectomized 8 months before immunization protected only 50 percent of the recipients. Further analysis showed that mice thymectomized 8 months before immunization failed to generate anti-YAS antibody response, whereas the antibody response of mice thymectomized 2 months before immunization did not differ from that of non-thymectomized age-matched control mice. The data suggest that the immune reaction of mice against xenogeneic YAS requires long-lived T 2 lymphocytes

Donor Safety in Haemapheresis: Development of an Internet-Based Registry for Comprehensive Assessment of Adverse Events from Healthy Donors.

Science.gov (United States)

Heuft, Hans-Gert; Fischer, Eike; Weingand, Tina; Burkhardt, Thomas; Leitner, Gerda; Baume, Hagen; Schmidt, Jörg-Peter; Buser, Andreas; Fauchald, Gabriele; Reinicke Voigt, Ute; Mansouri-Taleghani, Behrouz

2017-06-01

Currently, there is an extensive but highly inconsistent body of literature regarding donor adverse events (AEs) in haemapheresis. As the reports diverge with respect to types and grading of AEs, apheresis procedures and machines, the range of haemapheresis-related AEs varies widely from about 0.03% to 6.6%. The German Society for Transfusion Medicine and Immunohaematology (DGTI) formed a 'Haemapheresis Vigilance Working Party' (Arbeitsgemeinschaft Hämapheresevigilanz; AGHV) to create an on-line registry for comprehensive and comparable AE assessment with all available apheresis devices in all types of preparative haemapheresis: plasmapheresis (PLS), plateletpheresis (PLT), red blood cell apheresis, all kind of leukaphereses (autologous/allogeneic blood stem cell apheresis, granulocyte apheresis, lymphocyte/monocyte apheresis) and all possible types of multi-component apheresis. To ensure the comparability of the data, the AGHV adopted the 'Standard for Surveillance of Complications Related to Blood Donation' from the International Society for Blood Transfusion in cooperation with the International Haemovigilance Network (IHN) and the American Association of Blood Banks for AE acquisition and automated evaluation. The registry is embedded in a prospective observational multi-centre study with a study period of 7 years. A preliminary evaluation encompassed the time period from January, 2012 to December, 2015. During this time, the system proved to be safe and stable. Out of approximately 345,000 haemaphereses 16,477 AEs were reported (4.9%) from 20 participating centres. The majority of AEs occurred in PLSs (63%), followed by PLT (34.5%) and SC (2.2%). Blood access injuries (BAI) accounted for about 55% of the supplied AEs, whereas citrate toxicity symptoms, vasovagal reactions and technical events (e.g. disposable leakages, software failures) rather equally affected haemaphereses at 8-15%. Out of 12,348 finalized AEs, 8,759 (70.1%) were associated with a procedure

Lethal graft-versus-host disease: modification with allogeneic cultured donor cells

International Nuclear Information System (INIS)

Mauch, P.; Lipton, J.M.; Hamilton, B.; Obbagy, J.; Kudisch, M.; Nathan, D.; Hellman, S.

1984-01-01

The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences

Kidney transplant outcomes from older deceased donors

DEFF Research Database (Denmark)

Pippias, Maria; Jager, Kitty J; Caskey, Fergus

2018-01-01

As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor...

Interim Technical Report for Grant N00014-97-1-0199

National Research Council Canada - National Science Library

Williams, Tracey

1998-01-01

...) members and other eligible personnel into the National Marrow Donor Program Registry; support the DoD contingency requirement for unrelated bone marrow donations and tissue typed matched blood platelets...

Interim Technical Report for Grant N00014-97-1-0199

National Research Council Canada - National Science Library

Brown, R

1999-01-01

...) members and other eligible personnel into the National Marrow Donor Program Registry; support the DoD contingency requirement for unrelated bone marrow donations and tissue typed matched blood platelets...

Stimulation and inhibition of erythropoiesis in donors and hematopoietic effect in irradiated recipient

Energy Technology Data Exchange (ETDEWEB)

Ninkov, V; Piletic, O; Stepanovic, D [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia); Belgrade Univ. (Yugoslavia). Inst. of Histology)

1976-03-01

Regeneration dynamics in bone marrow and spleen was studied in rats after irradiation of 800 R and transfusion of bone marrow cells from donors treated in different ways. Priority of the microenvironment of the recipient or of the information obtained in cell donors with respect to further hematopoietic cell differentiation was studied in irradiated recipients. Rats irradiated with 800 R were used as recipients in the experiments. The donors of marrow cells were the rats with stimulated or inhibited erythropoiesis. Stimulation of erythropoiesis was induced by bleeding and experimental polycythemia was provoked by packed erythrocytes. According to our results, it can be concluded that the processes of postirradiation hematopoiesis after transplantation of the bone marrow cells depend on the number and proliferative state of both donors and recipient stem cells, and microenvironment, not excluding the information introduced with the donor cell transplant.

The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

Science.gov (United States)

Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

2013-03-01

Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

Bone marrow transplantation - a field in continuous development

International Nuclear Information System (INIS)

Pfeffer, P.F.

1975-01-01

The symptoms of the radiation syndrome are described briefly and the Vinca accident in 1958 is used as an illustration of the application of bone marrow transplantation as a treatment in radiation accidents. Thereafter the immunological problems arising when a permanent substitution of donor marrow is required are discussed. Greatest experience in bone marrow transplantation has been had in the treatment of aplastic anemia and acute leukemia. In these cases the recipient's bone marrow cells must be killed by whole body irradiation or by cyclophosphamide to preclude graft-host reaction. The removal of marrow from the donor and transplanting in the recipient are described, as is the progress of the patient in a typical case. The graft-host reaction is then discussed, as is the danger of secondary infections. In conclusion the long term results are evaluated and the future developments of the treatment discussed. (JIW)

Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

International Nuclear Information System (INIS)

Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

1983-01-01

Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras

Donating blood for research: a potential method for enhancing customer satisfaction of permanently deferred blood donors.

Science.gov (United States)

Waller, Daniel; Thijsen, Amanda; Garradd, Allira; Hayman, Jane; Smith, Geoff

2017-01-01

Each year, a large number of individuals in Australia are deferred from donating blood. A deferral may have a negative impact on donor satisfaction and subsequent word-of-mouth communication. The Australian Red Cross Blood Service (the Blood Service) is, therefore, investigating options for managing service interactions with deferred donors to maintain positive relationships. While public research institutes in Australia have established independent research donor registries, other countries provide programmes allowing deferred donors to donate blood for research via blood collection agencies. This study examined attitudes towards donating blood for research use in a sample of permanently deferred Australian donors. Donors permanently deferred because of a risk of variant Creutzfeldt-Jakob disease (n=449) completed a postal survey that examined attitudes towards research donation. The majority of participants were interested in donating blood for research (96%), and joining a registry of research donors (93%). Participants preferred to donate for transfusion or clinical research, and were willing to travel large distances. Results indicated that positive attitudes towards the Blood Service would be extended if the opportunity to donate blood was provided. These findings indicate a desire for continued engagement with the Blood Service despite deferral. Donating blood for research is a potential way of maintaining positive relationships with permanently deferred donors which also benefits the health research community. Through maintaining positive relationships with deferred donors, positive word-of-mouth activity can be stimulated. Further work is needed to determine the feasibility of implementing research donation through the Blood Service in Australia.

Effect of Massive Blood Transfusion on the Therapeutic Efficiency of Homogenic Bone Marrow in Acute Radiation Illness

Energy Technology Data Exchange (ETDEWEB)

Seraphimov-Dimitrov, V.; Decheva, Z.; Nedyalkova, M. [Institute of Haematology and Blood Transfusion, Sofia (Bulgaria)

1969-07-15

Simultaneously with bone-marrow transplantation, the authors replaced the blood of the lethally irradiated recipient animals with blood from the bone-marrow donor. From experiments on dogs and rabbits it became clear that replacing 86% of the recipient's blood with blood from the bone-marrow donor considerably reduces the therapeutic effect of bone-marrow transplantation. The authors consider that the main cause of the animals' early death in experiments combining bone-marrow transplantation and massive donor blood transfusions is a secondary syndrome resulting from the graft-versus-host reaction. This does not exclude the inverse possibility - that the development of a host-versus-graft reaction is due to the presence of a massive number of antigens of the donor blood in the blood of the recipient. (author)

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors.

Science.gov (United States)

Farhan, Roiya; Urbanowska, Elżbieta; Zborowska, Hanna; Król, Małgorzata; Król, Maria; Torosian, Tigran; Piotrowska, Iwona; Bogusz, Krzysztof; Skwierawska, Kamila; Wiktor-Jędrzejczak, Wiesław; Snarski, Emilian

2017-10-01

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 10 6 , 7.6 × 10 6 , and 7.3 × 10 6 , respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of

Can bone marrow differentiate into renal cells?

Science.gov (United States)

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

Science.gov (United States)

Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A

1996-09-01

For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and

The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

International Nuclear Information System (INIS)

Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

1983-01-01

Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest

Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program.

Directory of Open Access Journals (Sweden)

Noa Slater

2015-04-01

Full Text Available Measures of allele and haplotype diversity, which are fundamental properties in population genetics, often follow heavy tailed distributions. These measures are of particular interest in the field of hematopoietic stem cell transplant (HSCT. Donor/Recipient suitability for HSCT is determined by Human Leukocyte Antigen (HLA similarity. Match predictions rely upon a precise description of HLA diversity, yet classical estimates are inaccurate given the heavy-tailed nature of the distribution. This directly affects HSCT matching and diversity measures in broader fields such as species richness. We, therefore, have developed a power-law based estimator to measure allele and haplotype diversity that accommodates heavy tails using the concepts of regular variation and occupancy distributions. Application of our estimator to 6.59 million donors in the Be The Match Registry revealed that haplotypes follow a heavy tail distribution across all ethnicities: for example, 44.65% of the European American haplotypes are represented by only 1 individual. Indeed, our discovery rate of all U.S. European American haplotypes is estimated at 23.45% based upon sampling 3.97% of the population, leaving a large number of unobserved haplotypes. Population coverage, however, is much higher at 99.4% given that 90% of European Americans carry one of the 4.5% most frequent haplotypes. Alleles were found to be less diverse suggesting the current registry represents most alleles in the population. Thus, for HSCT registries, haplotype discovery will remain high with continued recruitment to a very deep level of sampling, but population coverage will not. Finally, we compared the convergence of our power-law versus classical diversity estimators such as Capture recapture, Chao, ACE and Jackknife methods. When fit to the haplotype data, our estimator displayed favorable properties in terms of convergence (with respect to sampling depth and accuracy (with respect to diversity

42 CFR 482.102 - Condition of participation: Patient and living donor rights.

Science.gov (United States)

2010-10-01

... health, disability, or life insurance may be affected; (8) The donor's right to opt out of donation at... donor rights. 482.102 Section 482.102 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION FOR...

Bone-Marrow Storage and Transplantation

International Nuclear Information System (INIS)

Costăchel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N.

1969-01-01

The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: • Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. • While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. • No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4°C. • DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. • In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: • The best time to administer bone marrow is between 24 and 48 h after irradiation. • No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. • Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. • In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of certain typical signs of secondary syndrome

Bone-Marrow Storage and Transplantation

Energy Technology Data Exchange (ETDEWEB)

Costachel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N. [Oncological Institute, Bucharest (Romania)

1969-07-15

The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: Bullet Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. Bullet While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. Bullet No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4 Degree-Sign C. Bullet DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. Bullet In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: Bullet The best time to administer bone marrow is between 24 and 48 h after irradiation. Bullet No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. Bullet Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. Bullet In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of

The devil is in the details: retention of recipient group A type 5 years after a successful allogeneic bone marrow transplant from a group O donor.

Science.gov (United States)

Cooling, Laura L W; Herrst, Michelle; Hugan, Sherri L

2018-01-01

ABO-incompatible (ABOi) hematopoietic stem cell transplants (HSCTs) can present challenges in the blood bank. During transplantation, patients receive components that are ABO-compatible with both the donor graft and recipient; this practice can strain group O red blood cell (RBC) inventories.1 In addition, there are risks for acute hemolysis at the time of infusion and in the early post-transplant period.1,2 In ABO major-incompatible bone marrow HSCTs, which contain significant quantities of donor RBCs that are ABOi with recipient plasma, it is common to perform a RBC depletion of the bone marrow in an effort to minimize hemolysis at the time of infusion.2 Furthermore, patients with high-titer ABO antibodies may undergo a prophylactic, pre-transplant plasma exchange to further reduce the risk of acute hemolysis, delayed RBC engraftment, and pure RBC aplasia.2-4 ABO minor-incompatible HSCTs, in which donor plasma is ABOi with the recipient, have less risk for hemolysis at the time of infusion but can result in transient hemolysis approximately 10-21 days post-transplant, especially in patients undergoing nonmyeloablative HSCT and/or patients who have not received methotrexate for graft-versus-host-disease (GVHD) prophylaxis.1-4 In these patients, viable donor B-lymphocytes in the graft may expand and produce ABO antibodies capable of hemolyzing patient RBCs.

Bone marrow transplantation for an infant with neutrophil dysfunction

Energy Technology Data Exchange (ETDEWEB)

Camitta, B M; Quesenberry, P J; Parkman, R; Boxer, L A; Stossel, T P; Cassady, J R; Rappeport, J M; Nathan, D G [Harvard Medical School, Boston, Mass. (USA); Tufts Univ., Boston, Mass. (USA). School of Medicine)

1977-01-01

A child with severe neutrophil dysfunction and intractable infections received bone marrow transplants from histocompatible siblings. After a first transplant preceded by cyclophosphamide (CY), antithymocyte serum (ATS) and procarbazine (PCB) preconditioning, there was no evidence for engraftment and autologous marrow function rapidly returned. Cell mediated lysis showed no evidence of patient sensitization against the marrow donor suggesting that graft rejection did not cause the transplant failure. A second transplant was performed utilizing another matched sibling donor. Total body irradiation was added to CY, ATS, and PCB for preconditioning after in vitro studies of the colony forming capacity (CFUsub(c)) of the patient's marrow cells showed normal sensitivity to radiation. Full engraftment ensued with correction of granulocyte function abnormalities. The patient eventually died of intractable pulmonary disease. Experience with this child suggests that cyclophosphamide alone may be insufficient preparation for marrow transplantation in some patients with non-neoplastic hematologic disorders. Experimental and clinical data supporting this contention are reviewed.

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

Science.gov (United States)

Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

2014-08-15

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

Science.gov (United States)

Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

2012-02-15

We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

Unrelated haematopoietic stem cell transplantation in Taiwan and beyond.

Science.gov (United States)

Yang, K L; Chang, C Y; Lin, S; Shyr, M H; Lin, P Y

2009-06-01

Since its inception in October 1993, the world-renowned Buddhist Tzu Chi Marrow Donor Registry has facilitated more than 1800 cases of stem cell donations for patients in 27 countries to date. Under the auspices of the Buddhist Tzu Chi Stem Cells Center (BTCSCC), the Registry (> 310,000 donors) offers, on average, one case of stem cell donation every day to national or international transplantation community. The accomplishment of the Registry stems from the philosophy and spirit of giving without reward that was inspired by its founder Dharma Master Cheng Yen, the Samaritan devotions of selfless voluntary stem cell donors and the efforts from a dedicated network of volunteer workers. Demographically speaking, slightly less than one third of the donations are provided to domestic patients and the rest to mainland China and countries in Asia, North America, Europe, Middle East, Oceania, and South Africa. While most of the patients belong to the Oriental ethnic group, a few of the patients are non-Oriental. In addition to the Registry, a non-profit umbilical cord blood (UCB) bank is operating since 2002 to provide a complimentary role for patients unable to identify appropriate bone marrow stem cell donors in the Registry in time. To date, with an inventory of over 12,000 units of UCB cryopreserved in the Tzu Chi Cord Blood Bank, 47 units have been employed in 37 cases of transplantation for both paediatric and adult patients domestically and internationally. The fact that Buddhist Tzu Chi Marrow Donor Registry and Cord Blood Bank are established and operating without governmental financial support is unique and special. To facilitate haematopoietic stem cells to its domestic patients experiencing financial burdens, the BTCSCC offers financial aids to the underprivileged for their medical relief. This humanitarian approach and compassion is definitely a role model for many countries in the world.

The Brain Health Registry: An internet-based platform for recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies.

Science.gov (United States)

Weiner, Michael W; Nosheny, Rachel; Camacho, Monica; Truran-Sacrey, Diana; Mackin, R Scott; Flenniken, Derek; Ulbricht, Aaron; Insel, Philip; Finley, Shannon; Fockler, Juliet; Veitch, Dallas

2018-05-08

Recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies and clinical trials limit the development of new treatments. Widespread Internet use allows data capture from participants in an unsupervised setting. The Brain Health Registry, a website and online registry, collects data from participants and their study partners. The Brain Health Registry obtains self and study partner report questionnaires and neuropsychological data, including the Cogstate Brief Battery, Lumos Labs Neurocognitive Performance Test, and MemTrax Memory Test. Participants provide informed consent before participation. Baseline and longitudinal data were obtained from nearly 57,000 and 28,000 participants, respectively. Over 18,800 participants were referred to, and nearly 1800 were enrolled in, clinical Alzheimer's disease and aging studies, including five observational studies and seven intervention trials. Online assessments of participants and study partners provide useful information at relatively low cost for neuroscience studies and clinical trials and may ultimately be used in routine clinical practice. Copyright © 2018 the Alzheimer's Association. All rights reserved.

Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice

International Nuclear Information System (INIS)

Brecher, G.; Ansell, J.D.; Micklem, H.S.; Tjio, J.H.; Cronkite, E.P.

1982-01-01

The widely held view that transfused bone marrow cells will not proliferate in normal mice, not exposed to irradiation or other forms of bone marrow ablation, was reinvestigated. Forty million bone marrow cells from male donors were given to female recipients on each of 5 consecutive days, 5 to 10 times the number customarily used in the past. When the recipients were examined 2-13 weeks after the last transfusion, donor cells were found to average 16-25% of total marrow cells. Similar percentages of donor cells were found when variants of the enzyme phosphoglycerate kinase determined electrophoretically were used for identification of donor and recipient cells. Evidence is presented that the proportion of donor cells is compatible with a nonlinear dependence on the number of cells transfused over the range tested - i.e., 20-200 million bone marrow cells injected intravenously. Special proliferative sites thus do not appear to be required

What Is a Bone Marrow Transplant?

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... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... Copyright © 1996-2018 National Marrow Donor Program. All Rights Reserved.

Cord blood collection and banking from a population with highly diverse geographic origins increase HLA diversity in the registry and do not lower the proportion of validated cord blood units: experience of the Marseille Cord Blood Bank.

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Bordoni, C; Magalon, J; Gilbertas, C; Gamerre, M; Le Coz, P; Berthomieu, M; Chabannon, C; Di Cristofaro, J; Picard, C

2015-04-01

Several Cord Blood (CB) Bank studies suggested that ethnicity impaired CB unit (CBU) qualification. The Bone Marrow Donors Worldwide registries present an over-representation of unrelated donors (UD) from Northwestern European descent. This raises the question of equality of access to hematopoietic stem cells transplant, especially in the Mediterranean zone, which has taken in many waves of immigration. The aim of our study is to address whether, in the Marseille CB Bank, CBU qualification rate is impaired by geographic origin. The study compared biological characteristics of 106 CBU disqualified for total nucleated cell (TNC) count (dCBU) and 136 qualified CBU in relation to registry enrichment and haplotype origin. A high proportion (>80%) of both dCBU and CBU had at least one non-European haplotype and enrich CB and UD registries to a higher extent than those with two European haplotypes (Pdiverse Mediterranean origins do not have an impact on the CBU qualification rate. Partnership with Mediterranean birth clinics with highly trained staff is a reasonable option to increase the HLA diversity of CB Bank inventories and to improve the representation of minorities.

Lasting engraftment of histoincompatible bone marrow cells in dogs

International Nuclear Information System (INIS)

Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

1981-01-01

Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed

Lasting engraftment of histoincompatible bone marrow cells in dogs

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Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

1981-05-01

Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

Lasting engraftment of histoincompatible bone marrow cells in dogs

Energy Technology Data Exchange (ETDEWEB)

Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

1981-05-01

Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

A perspective on the selection of unrelated donors and cord blood units for transplantation

Science.gov (United States)

Spellman, Stephen R.; Eapen, Mary; Logan, Brent R.; Mueller, Carlheinz; Rubinstein, Pablo; Setterholm, Michelle I.; Woolfrey, Ann E.; Confer, Dennis L.; Hurley, Carolyn K.

2012-01-01

Selection of a suitable graft for allogeneic hematopoietic stem cell transplantation involves consideration of both donor and recipient characteristics. Of primary importance is sufficient donor-recipient HLA matching to ensure engraftment and acceptable rates of GVHD. In this Perspective, the National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research provide guidelines, based on large studies correlating graft characteristics with clinical transplantation outcomes, on appropriate typing strategies and matching criteria for unrelated adult donor and cord blood graft selection. PMID:22596257

42 CFR 482.90 - Condition of participation: Patient and living donor selection.

Science.gov (United States)

2010-10-01

... selected to receive a transplant, the center must document in the patient's medical record the patient... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Patient and living... Condition of participation: Patient and living donor selection. The transplant center must use written...

Natural history and Predictors of Progression to Sjögren's Syndrome Among Participants of the SICCA registry

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Shiboski, Caroline H; Baer, Alan N; Shiboski, Stephen C

2018-01-01

found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti-SSA/B antibodies, were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections......BACKGROUND/PURPOSE: To explore changes in the phenotypic features of Sjoögren's syndrome (SS), and in SS status among participants in the Sjoögren's International Collaborative Clinical Alliance (SICCA) registry over a 2 to 3-year interval. METHODS: All participants in the SICCA registry who were...

Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

International Nuclear Information System (INIS)

Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

1983-01-01

The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

Seleção de doador de medula óssea ou sangue periférico Bone marrow or peripheral blood donor selection

Directory of Open Access Journals (Sweden)

Noemi F. Pereira

2010-05-01

Full Text Available A compatibilidade HLA é o fator mais valorizado na escolha do doador de medula óssea voluntário, preconizando-se a realização de HLA de alta resolução nos locos HLA-A,B,C, DRB1 e DQB1. Tem sido dado preferência para o doador com consanguinidade alélica 8x8 (A,B,C, DRB1. Na presença de incompatibilidade na classe-I sugere-se a busca de doador com compatibilidade DQB1 (9x10. Já as incompatibilidades dos locos DPB1 não constituem critério de exclusão de doador, exceto quando existir presença de anticorpo contra o loco HLA-DP do doador.The HLA system is considered the most important factor in choosing a volunteer bone marrow donor with the recommendation of performing high resolution HLA tests for the HLA-A, B, C, DRB1 and DQB1 loci. A preference has been given for donor 8x8 (A, B, C, DRB1 allele matching. In the presence of class-I incompatibility a search for DQB1 (9x10 donor compatibility is suggested. The incompatibility of the DPB1 locus does not constitute exclusion of the donor, except when there is the presence of antibodies against the HLA-DP locus of the donor.

Effects and Complications of Bone-Marrow Transplantation in Man

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Mathe, G.; Schwarzenberg, L.; Miel, J.L. A; Schneider, M.; Cattan, A.; Schlumberger, J. R. [Institut de cancerologie et immunogenetique, Hopital Paul Brousse, Villejuif (France)

1969-07-15

Full text: Allogenic bone-marrow grafting in 24 human leukaemic subjects is described. The graft failed in 7 cases and took in 17 cases. In the latter group, all 17 cases were complicated by the secondary syndrome which was-fatal in 13 cases and controlled in 4 cases. The immunogenetic and immunological factors determining the establishment and evolution of haematological radiochimeras in man are discussed. The choice of donor is fundamental. Three tests are effective in donor selection, the indirect histocompatibility test, the leucocyte antigen test and the reaction of donor and recipient leucocytes in the dermis of an irradiated hamster. When marrow from several donors is transfused, the recipient spontaneously selects the genetically nearest. It seems likely there is more chance of finding a suitable donor among genetically related subjects than among those who are unrelated. The frequency of graft take seems slightly lower in recipients who have previously received blood transfusions. Total bone-marrow graft is associated with specific tolerance towards donor tissues. This is paralleled by the production in the chimera of immunoglobulins produced by the graft. The secondary syndrome seems, as in animals, to be related essentially to the graft-versus-host reaction. It is convenient to distinguish among its various manifestations, on the one hand, those lesions which are readily controlled such as hepatitis or erythrodermia associated with infiltration and proliferation of immunologically competent cells from the graft and, on the other hand, immune insufficiency with regard to micro-organisms, especially viruses and Candida albicans. This latter group, the mechanism of which is complex, still eludes attempts at preventive and curative control. The use of multiple donors and the administration of cortisone during marrow transfusion and A-methopterin and/or cyclophosphamide in the days following transfusions; seem to have reduced the severity of the secondary

[Information booklet for related hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Science.gov (United States)

Polomeni, Alice; Tardieu, Laure; Ainaoui, Malika; Andrianne, Christelle; Bancillon, Nelly; Chapel, Valerie; Chevallier, Nathalie; Evrard, Solène; Fournier, Isabelle; Gargallo, Guillaume; Godin, Sandrine; Issarni, Dominique; Le Bars, Laetitia; Renaud, Barbara; Yakoub-Agha, Ibrahim; Wallart, Anne; De Bentzmann, Natacha

2017-12-01

Providing information to living donors is first and foremost a legal obligation as well as an ethical one, not to mention necessary to health care provision. It's been shown that quality of information concerning the procedure's practical aspects, scheduling of clinical tests and examinations, withdrawing stem cells for the donation, post-donation symptoms, and support provided by healthcare teams, directly impacts the donor's quality of experience. Taking this into consideration our group decided it was essential to create an informational support for donors in the form of a booklet to be provided in different hematopoietic stem cell transplant centers across France. In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allergenic hematopoietic stem cell transplantation clinical practices harmonization workshops. As part of these workshops, our group worked collectively to develop a basis of indispensable information to be included in the booklet and presented using clear and accessible language. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Factors controlling the engraftment of transplanted dog bone marrow cells

International Nuclear Information System (INIS)

Vriesendorp, H.M.; Klapwyk, W.M.; Heidt, P.J.; Hogeweg, B.; Zurcher, C.; Bekkum, D.W. van

1982-01-01

The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrme was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility comples (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rateof hemopoietic recovery correlated with the number of BM cells given. Approximtely 2 x 10 7 autologous and 1 x 10 8 MHC identical BM cells.kg -1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterine inertia in female dogs after 7.5 GY TBI. Fertility in males or females was not changed by radiation. An increase of pancreas fibrosis was noted in dogs receiving fractions of 6.0 Gy TBI. (author)

Bone marrow transplantation for treatment of radiation disease. Problems involved

International Nuclear Information System (INIS)

Fliedner, T.M.

1992-01-01

Transplantation of bone marrow cells still is one of the major means available for treatment of radiation injuries. The decisive indication is the diagnostic of irreversible damage to the hemopoietic stem cells, which becomes manifest about 5 or 6 days after exposure, by severe granulocytopenia and simultaneous, progressive thrombopenia. The radiation dose provoking such severe injury is estimated to be at least 9-10 Gy of homogeneous whole-body irradiation. Preparatory measures for transplantation include proof of tissue compatibility of donor and patient, sufficient immunosuppression prior to and/or after irradiation and bone marrow transplantation. The donor's marrow should be free of T-cells. In spite of preparatory treatment, complications such as immunological reactions or disturbance of organ functions are to be very probable. These are treated according to therapy protocols. (orig./MG) [de

The impact of disclosure on donor gamete participants: donors, intended parents and offspring.

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Greenfeld, Dorothy A

2008-06-01

The present review examines recent publications that provide insight into how the trend toward nonanonymity and disclosure in gamete donation impacts donors, intended parents, and their donor-conceived children. Recent findings show an increase in donor programs that offer open-identity between donors and offspring. The psychological needs of gamete donors and their attitudes toward disclosure are increasingly given consideration. Qualitative research on how parents of donor gamete offspring make decisions about disclosure reveals that even when couples initially disagree about disclosing to offspring, most ultimately come to a united disclosure decision. The literature on the impact of disclosure on donor gamete offspring has extended to include children conceived through embryo donation and children born as a result of surrogacy. The absence of genetic or gestational link between parents and their child does not have a negative impact on parent-child relationships. Parents through surrogacy tend to disclose the method of family creation to their child, whereas parents through embryo donation tend to be secretive about their child's origins. The trend toward greater openness in gamete donation has been accompanied by an increase in programs offering open-identity donation. In addition, the psychological needs of gamete donors and their attitudes toward disclosure are increasingly being given consideration. Parents of donor gamete offspring give careful thought to their disclosure decisions, and the psychological well being of donor-conceived children does not seem to be impacted by those decisions.

Specific allogeneic unresponsiveness in irradiated dogs reconstituted with autologous bone marrow

International Nuclear Information System (INIS)

Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.; Ferrebee, J.W.

1980-01-01

Hemopoietic reconstitution of supralethally irradiated adult dogs of the Cooperstown colony with their own stored bone marrow can produce long-term unresponsiveness to DLA-identical kidney allografts with no need for any additional immunosuppression. Eleven of 18 kidneys transplanted 12 h after replacement of autologous marrow into irradiated recipients currently survive with normal function for as long as 1417 d; 8 of 13 organs transplanted 28 h after marrow replacement, and 8 of 13 organs transplanted 36 h after marrow injection, currently survive up to 502 d, with no further treatment. Alterations in the timing and sequence of each procedure decrease the incidence of unresponsiveness. Survival and function of the kidney allografts were not affected by the rejection of successive skin grafts from the kidney donor. Skin grafts from other DLA-identical donors and DLA-incompatible skin grafts were rejected by the same recipients in uniform fashion

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

Directory of Open Access Journals (Sweden)

Jill A Hollenbach

Full Text Available We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752 from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs, and the human leukocyte antigen (HLA genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents' information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

Science.gov (United States)

Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

2015-01-01

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

Expectations and experiences of gamete donors and donor-conceived adults searching for genetic relatives using DNA linking through a voluntary register.

Science.gov (United States)

van den Akker, O B A; Crawshaw, M A; Blyth, E D; Frith, L J

2015-01-01

What are the experiences of donor-conceived adults and donors who are searching for a genetic link through the use of a DNA-based voluntary register service? Donor-conceived adults and donors held positive beliefs about their search and although some concerns in relation to finding a genetically linked relative were reported, these were not a barrier to searching. Research with donor-conceived people has consistently identified their interest in learning about-and in some cases making contact with-their donor and other genetic relatives. However, donor-conceived individuals or donors rarely have the opportunity to act on these desires. A questionnaire was administered for online completion using Bristol Online Surveys. The survey was live for 3 months and responses were collected anonymously. The survey was completed by 65 donor-conceived adults, 21 sperm donors and 5 oocyte donors who had registered with a DNA-based voluntary contact register in the UK. The questionnaire included socio-demographic questions, questions specifically developed for the purposes of this study and the standardized Aspects of Identity Questionnaire (AIQ). Motivations for searching for genetic relatives were varied, with the most common reasons being curiosity and passing on information. Overall, participants who were already linked and those awaiting a link were positive about being linked and valued access to a DNA-based register. Collective identity (reflecting self-defining feelings of continuity and uniqueness), as assessed by the AIQ, was significantly lower for donor-conceived adults when compared with the donor groups (P 0.05) for donor-conceived adults. Participants were members of a UK DNA-based registry which is unique. It was therefore not possible to determine how representative participants were of those who did not register for the service, those in other countries or of those who do not seek information exchange or contact. This is the first survey exploring the

The association of donor and recipient age with graft survival in paediatric renal transplant recipients in a European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplantation Association Registry study

DEFF Research Database (Denmark)

Chesnaye, Nicholas C.; Van Stralen, Karlijn J.; Bonthuis, Marjolein

2017-01-01

from the ESPN/ERA-EDTA Registry. The effect of donor and recipient age combinations on 5-year graft-failure risk, stratified by donor source, was estimated using Kaplan-Meier survival curves and Cox regression, while adjusting for sex, primary renal diseases with a high risk of recurrence, pre......Background The impact of donor age in paediatric kidney transplantation is unclear. We therefore examined the association of donor-recipient age combinations with graft survival in children. Methods Data for 4686 first kidney transplantations performed in 13 countries in 1990-2013 were extracted......-emptive transplantation, year of transplantation and country. Results The risk of graft failure in older living donors (50-75 years old) was similar to that of younger living donors {adjusted hazard ratio [aHR] 0.74 [95% confidence interval (CI) 0.38-1.47]}. Deceased donor (DD) age was non-linearly associated with graft...

Total lymphatic irradiation and bone marrow in human heart transplantation

International Nuclear Information System (INIS)

Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

1984-01-01

Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

1982-01-01

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

Science.gov (United States)

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

Energy Technology Data Exchange (ETDEWEB)

James, N D; Apperley, J F; Kam, K C; Mackinnon, S; Goldman, J M; Goolden, A W.G.; Sikora, K [Royal Postgraduate Medical School, London (UK)

1989-03-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author).

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

International Nuclear Information System (INIS)

James, N.D.; Apperley, J.F.; Kam, K.C.; Mackinnon, S.; Goldman, J.M.; Goolden, A.W.G.; Sikora, K.

1989-01-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author)

Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells

International Nuclear Information System (INIS)

Yasumizu, R.; Onoe, K.; Iwabuchi, K.; Ogasawara, M.; Fujita, M.; Okuyama, H.; Good, R.A.; Morikawa, K.

1985-01-01

Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study

Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia

International Nuclear Information System (INIS)

Matsue, K.; Niki, T.; Shiobara, S.; Ueda, M.; Ohtake, S.; Mori, T.; Matsuda, T.; Harada, M.

1990-01-01

We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation

Influences on participant reporting in the World Health Organisation drugs exposure pregnancy registry; a qualitative study.

Science.gov (United States)

Allen, Elizabeth N; Gomes, Melba; Yevoo, Lucy; Egesah, Omar; Clerk, Christine; Byamugisha, Josaphat; Mbonye, Anthony; Were, Edwin; Mehta, Ushma; Atuyambe, Lynn M

2014-10-31

The World Health Organisation has designed a pregnancy registry to investigate the effect of maternal drug use on pregnancy outcomes in resource-limited settings. In this sentinel surveillance system, detailed health and drug use data are prospectively collected from the first antenatal clinic visit until delivery. Over and above other clinical records, the registry relies on accurate participant reports about the drugs they use. Qualitative methods were incorporated into a pilot registry study during 2010 and 2011 to examine barriers to women reporting these drugs and other exposures at antenatal clinics, and how they might be overcome. Twenty-seven focus group discussions were conducted in Ghana, Kenya and Uganda with a total of 208 women either enrolled in the registry or from its source communities. A question guide was designed to uncover the types of exposure data under- or inaccurately reported at antenatal clinics, the underlying reasons, and how women prefer to be asked questions. Transcripts were analysed thematically. Women said it was important for them to report everything they had used during pregnancy. However, they expressed reservations about revealing their consumption of traditional, over-the-counter medicines and alcohol to antenatal staff because of anticipated negative reactions. Some enrolled participants' improved relationship with registry staff facilitated information sharing and the registry tools helped overcome problems with recall and naming of medicines. Decisions about where women sought care, which influenced medicines used and antenatal clinic attendance, were influenced by pressure within and outside of the formal healthcare system to conform to conflicting behaviours. Conversations also reflected women's responsibilities for producing a healthy baby. Women in this study commonly take traditional medicines in pregnancy, and to a lesser extent over-the-counter medicines and alcohol. The World Health Organisation pregnancy registry

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

International Nuclear Information System (INIS)

Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

Does Social Capital Explain Community-Level Differences in Organ Donor Designation?

Science.gov (United States)

Ladin, Keren; Wang, Rui; Fleishman, Aaron; Boger, Matthew; Rodrigue, James R

2015-09-01

The growing shortage of life-saving organs has reached unprecedented levels, with more than 120,000 Americans waiting for them. Despite national attempts to increase organ donation and federal laws mandating the equitable allocation of organs, geographic disparities remain. A better understanding of the contextual determinants of organ donor designation, including social capital, may enhance efforts to increase organ donation by raising the probability of collective action and fostering norms of reciprocity and cooperation while increasing costs to defectors. Because community-level factors, including social capital, predict more than half the variation in donor designation, future interventions should tailor strategies to specific communities as the unit of intervention. The growing shortage of organs has reached unprecedented levels. Despite national attempts to increase donation and federal laws mandating the equitable allocation of organs, their availability and waiting times vary significantly nationwide. Organ donor designation is a collective action problem in public health, in which the regional organ supply and average waiting times are determined by the willingness of individuals to be listed as organ donors. Social capital increases the probability of collective action by fostering norms of reciprocity and cooperation while increasing costs to defectors. We examine whether social capital and other community-level factors explain geographic variation in organ donor designation rates in Massachusetts. We obtained a sample of 3,281,532 registered drivers in 2010 from the Massachusetts Department of Transportation Registry of Motor Vehicles (MassDOT RMV). We then geocoded the registry data, matched them to 4,466 census blocks, and linked them to the 2010 US Census, the American Community Survey (ACS), and other sources to obtain community-level sociodemographic, social capital (residential segregation, voter registration and participation, residential

The healthy donor effect impacts self-reported physical and mental health - results from the Danish Blood Donor Study (DBDS)

DEFF Research Database (Denmark)

Rigas, A S; Skytthe, A; Erikstrup, C

2017-01-01

AIMS: This study aimed at quantifying the healthy donor effect by comparing self-perceived mental and physical health between blood donors and non-donors. BACKGROUND: In theory, the selection process known as the healthy donor effect should result in better self-perceived, health-related quality...... of life in donors than in non-donors. METHODS: The Short Form-12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified......-perceived mental health was associated with a blood donor. With the increase in age, better self-perceived physical health was associated with blood donation....

Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

Science.gov (United States)

Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

2013-03-01

Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

Homing of bone marrow lymphoid cells

International Nuclear Information System (INIS)

Yoshida, Y.; Osmond, D.G.

1978-01-01

DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

Technical Report of the National Marrow Donor Program

National Research Council Canada - National Science Library

Setterholm, Michelle

2008-01-01

... a nationwide contingency response plan. Rapid Identification of Matched Donors: Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event...

In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice.

Science.gov (United States)

Chou, Shiu-Huey; Kuo, Tom K; Liu, Ming; Lee, Oscar K

2006-03-01

Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from human bone marrow and possess the potential to differentiate into progenies of embryonic mesoderm. However, current evidence is based predominantly on in vitro experiments. We used a murine model of in utero transplantation (IUT) to study the engraftment capabilities of human MSCs. MSCs were obtained from bone marrow by negative immunoselection and limiting dilution, and were characterized by flow cytometry and by in vitro differentiation into osteoblasts, chondrocytes, and adipocytes. MSCs were transplanted into fetal mice at a gestational age of 14 days. Engraftment of human MSCs was determined by flow cytometry, polymerase chain reaction, and fluorescence in situ hybridization (FISH). MSCs engrafted into tissues originating from all three germ layers and persisted for up to 4 months or more after delivery, as evidenced by the expression of the human-specific beta-2 microglobulin gene and by FISH for donor-derived cells. Donor-derived CD45+ cells were detectable in the peripheral blood of recipients, suggesting the participation of MSCs in hematopoiesis at the fetal stage. This model can further serve to evaluate possible applications of MSCs. Copyright 2006 Orthopaedic Research Society.

The Human Tissue Act 2004 and the child donor.

Science.gov (United States)

Baston, Jenny

2009-05-01

In 2001, the inquiry panel appointed to investigate the removal, retention and disposal of human organs and tissues at the Royal Liverpool Children's Hospital published its report. The panel's recommendations led to a new approach to consent for organ removal and storage under the new Human Tissue Act 2004. For child bone marrow donors, the new consent process requires all donor children or their parent to undergo a separate assessment before the bone marrow donation. They must be assessed by an accredited assessor who will submit a recommendation to the Human Tissue Authority for consideration. The unfortunate circumstances highlighted in the inquiry have led to changes to law, practice and culture that are benefiting other children and families.

Cancer Incidence and Mortality in a Cohort of US Blood Donors: A 20-Year Study

International Nuclear Information System (INIS)

Vahidnia, F.; Busch, M. P.; Custer, B.; Hirschler, N. V.; Chinn, A.; Agapova, M.; Busch, M. P.; Custer, B.

2013-01-01

Blood donors are considered one of the healthiest populations. This study describes the epidemiology of cancer in a cohort of blood donors up to 20 years after blood donation. Records from donors who participated in the Retroviral Epidemiology Donor Study (REDS, 1991-2002) at Blood Centers of the Pacific (BCP), San Francisco, were linked to the California Cancer Registry (CCR, 1991-2010). Standardized incidence ratios (SIR) were estimated using standard US 2000 population, and survival analysis used to compare all-cause mortality among donors and a random sample of non donors with cancer from CCR. Of 55,158 eligible allogeneic blood donors followed-up for 863,902 person-years, 4,236 (7.7%) primary malignant cancers were diagnosed. SIR in donors was 1.59 (95% CI = 1.54,1.64). Donors had significantly lower mortality (adjusted HR = 0.70, 95% CI = 0.66-0.74) compared with non donor cancer patients, except for respiratory system cancers (adjusted HR = 0.93, 95% CI = 0.82-1.05). Elevated cancer incidence among blood donors may reflect higher diagnosis rates due to health seeking behavior and cancer screening in donors. A “healthy donor effect” on mortality following cancer diagnosis was demonstrated. This population-based database and sample repository of blood donors with long-term monitoring of cancer incidence provides the opportunity for future analyses of genetic and other bio markers of cancer

Succesful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow

International Nuclear Information System (INIS)

Meredith, R.F.; OKunewick, J.P.; Kuhnert, P.M.; Brozovich, B.J.; Weaver, E.V.

1978-01-01

The therapeutic effectiveness on murine viral-leukemia of allogeneic or hybrid hematopoietic cells transplanted from leukemia-virus resistant donors was evaluated and compared with that of syngeneic cells. Transplantation of syngeneic cells gave no protection to the viral-leukemic mice. Transplantation of spleen cells from allogeneic donors resulted in early deaths of both leukemic and non-leukemic recipients. Transplantation of hybrid spleen cells resulted in no long-term survival of the leukemic mice. However, there were a number of long-term survivors among the leukemic recipients of allogeneic or hybrid marrow cells. Engraftment of allogeneic marrow resulted in a large number of survivors. Hybrid marrow recipients showed an even better survival, but some leukemia relapses. Tests of the longterm survivors revealed that even though they gave no evidence of leukemia they still harbored the active virus. This suggests that the mechanism of protection may be related to some inherent characteristic of the donor cells rendering them refractory to viral transformation. A difference in graft-versus-host (GvH) response between the leukemic and control mice was also found after transplantation of allogeneic cells. While all of the controls died of GvH reaction, none of the leukemic recipients showed severe GvH response, suggesting a possible effect of the leukemia on histocompatibility. No GvH reaction was found with hybrid marrow engraftment, although some of the leukemic recipients reconstituted with F 1 cells did die of leukemic relapse. (author)

Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

International Nuclear Information System (INIS)

Onoe, K.; Good, R.A.; Yamamoto, K.

1986-01-01

Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, [BR----AKR], as well as syngeneic marrow cells, [AKR----AKR], showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, [B10----AKR], [B10.AQR----AKR], [B10.A(4R)----AKR], or [B10.A(5R)----AKR], were almost completely unresponsive in DTH and antibacterial immunity. However, when [B10----AKR] H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type

Clinical verification of genetic results returned to research participants: findings from a Colon Cancer Family Registry.

Science.gov (United States)

Laurino, Mercy Y; Truitt, Anjali R; Tenney, Lederle; Fisher, Douglass; Lindor, Noralane M; Veenstra, David; Jarvik, Gail P; Newcomb, Polly A; Fullerton, Stephanie M

2017-11-01

The extent to which participants act to clinically verify research results is largely unknown. This study examined whether participants who received Lynch syndrome (LS)-related findings pursued researchers' recommendation to clinically verify results with testing performed by a CLIA-certified laboratory. The Fred Hutchinson Cancer Research Center site of the multinational Colon Cancer Family Registry offered non-CLIA individual genetic research results to select registry participants (cases and their enrolled relatives) from 2011 to 2013. Participants who elected to receive results were counseled on the importance of verifying results at a CLIA-certified laboratory. Twenty-six (76.5%) of the 34 participants who received genetic results completed 2- and 12-month postdisclosure surveys; 42.3% of these (11/26) participated in a semistructured follow-up interview. Within 12 months of result disclosure, only 4 (15.4%) of 26 participants reported having verified their results in a CLIA-certified laboratory; of these four cases, all research and clinical results were concordant. Reasons for pursuing clinical verification included acting on the recommendation of the research team and informing future clinical care. Those who did not verify results cited lack of insurance coverage and limited perceived personal benefit of clinical verification as reasons for inaction. These findings suggest researchers will need to address barriers to seeking clinical verification in order to ensure that the intended benefits of returning genetic research results are realized. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Molecular profile and cellular characterization of human bone marrow mesenchymal stem cells: donor influence on chondrogenesis.

Science.gov (United States)

Cicione, Claudia; Díaz-Prado, Silvia; Muiños-López, Emma; Hermida-Gómez, Tamara; Blanco, Francisco J

2010-01-01

The use of autologous or allogenic stem cells has recently been suggested as an alternative therapeutic approach for treatment of cartilage defects. Bone marrow mesenchymal stem cells (BM-MSCs) are well-characterized multipotent cells that can differentiate into different cell types. Understanding the potential of these cells and the molecular mechanisms underlying their differentiation should lead to innovative protocols for clinical applications. The aim of this study was to evaluate the usefulness of surface antigen selection of BM-MSCs and to understand the mechanisms underlying their differentiation. MSCs were isolated from BM stroma and expanded. CD105+ subpopulation was isolated using a magnetic separator. We compared culture-expanded selected cells with non-selected cells. We analyzed the phenotypic profiles, the expression of the stem cell marker genes Nanog, Oct3/4, and Sox2 and the multi-lineage differentiation potential (adipogenic, osteogenic, and chondrogenic). The multi-lineage differentiation was confirmed using histochemistry, immunohistochemistry and/or real-time polymerase chain reaction (qPCR) techniques. The selected and non-selected cells displayed similar phenotypes and multi-lineage differentiation potentials. Analyzing each cell source individually, we could divide the six donors into two groups: one with a high percentage of CD29 (β1-integrin) expression (HL); one with a low percentage of CD29 (LL). These two groups had different chondrogenic capacities and different expression levels of the stem cell marker genes. This study showed that phenotypic profiles of donors were related to the chondrogenic potential of human BM-MSCs. The chondrogenic potential of donors was related to CD29 expression levels. The high expression of CD29 antigen seemed necessary for chondrogenic differentiation. Further investigation into the mechanisms responsible for these differences in BM-MSCs chondrogenesis is therefore warranted. Understanding the mechanisms

Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID.

Science.gov (United States)

Stirnadel-Farrant, Heide; Kudari, Mahesh; Garman, Nadia; Imrie, Jessica; Chopra, Bikramjit; Giannelli, Stefania; Gabaldo, Michela; Corti, Ambra; Zancan, Stefano; Aiuti, Alessandro; Cicalese, Maria Pia; Batta, Rohit; Appleby, Jonathan; Davinelli, Mario; Ng, Pauline

2018-04-06

Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. Existing primary immunodeficiency registries are tailored to transplantation outcomes and do not capture the breadth of safety and efficacy endpoints required by the EMA for the long-term monitoring of gene therapies. Furthermore, for extended monitoring of Strimvelis, the young age of children treated, small patient numbers, and broad geographic distribution of patients all increase the risk of loss to follow-up before sufficient data have been collected. Establishing individual investigator sites would be impractical and uneconomical owing to the small number of patients from each location receiving Strimvelis. An observational registry has been established to monitor the safety and effectiveness of Strimvelis in up to 50 patients over a minimum of 15 years. To address the potential challenges highlighted above, data will be collected by a single investigator site at Ospedale San Raffaele (OSR), Milan, Italy, and entered into the registry via a central electronic platform. Patients/families and the patient's local physician will also be able to submit healthcare information directly to the registry using a uniquely designed electronic platform. Data entry will be monitored by a Gene Therapy Registry Centre (funded by GlaxoSmithKline) who will ensure that necessary information is collected and flows between OSR, the patient/family and the patient's local healthcare provider. The Strimvelis registry sets a precedent for the safety monitoring of future gene therapies. A unique, patient-focused design has been implemented to address the challenges of long-term follow-up of patients treated with gene therapy for a rare disease. Strategies to

Infusion of Sibling Marrow in a Patient with Purine Nucleoside Phosphorylase Deficiency Leads to Split Mixed Donor Chimerism and Normal Immunity

Directory of Open Access Journals (Sweden)

Laura Yeates

2017-06-01

Full Text Available Purine nucleoside phosphorylase (PNP deficiency, a rare autosomal recessive metabolic disease causes combined immunodeficiency and developmental delay, hypotonia, and spasticity. Patients present with recurrent infections associated with T-lymphocytopenia, characteristically presenting later than patients with classical severe combined immunodeficiency (SCID. PNP, with adenosine deaminase (ADA, is part of the purine salvage pathway. The only curative therapy is hematopoietic stem cell transplantation. Myeloablative conditioning is recommended to prevent rejection caused by residual immune function. However, HLA-identical sibling stem cell infusions in ADA-SCID result in some donor stem cell engraftment and long-term thymopoiesis. We report a patient with PNP deficiency, who received HLA-identical sibling marrow without chemotherapy because of disseminated cytomegalovirus (CMV infection. The patient presented at 14 months of age following recurrent infections, from early infancy, with persistent irritability, developmental delay, and hypotonia. She had neutropenia, pan-lymphocytopenia, and hypogammaglobulinemia with low plasma urate and erythrocyte PNP activity. Diagnosis was confirmed with a homozygous mutation in PNP. The patient was viremic with CMV detected in blood and CSF by PCR. Dual antiviral therapy improved the clinical condition and reduced the viral load. In view of the disseminated CMV infection, the decision was made to infuse stem cells without any pre-conditioning chemotherapy. She received a matched sibling donor unconditioned stem cell infusion at 16 months of age. The post-transplant course was uneventful. Blood PCR became negative for CMV. Global hypotonia persisted, although with significant improvement in irritability. At 4 years of age and 29 months post-transplant, the patient demonstrated normal T-lymphocyte and natural killer cell numbers. Recent thymic emigrants represented 12% of the total T

Eighteen years experience of granulocyte donations-acceptable donor safety?

Science.gov (United States)

Axdorph Nygell, Ulla; Sollén-Nilsson, Agneta; Lundahl, Joachim

2015-10-01

Granulocyte transfusions are given to patients with life-threatening infections, refractory to treatment. The donors are stimulated with corticosteroids ± granulocyte colony stimulating factor (G-CSF). However, data regarding the donors' safety is sparse. The objective was therefore to evaluate short- and long-term adverse events (AE) in G-CSF stimulated donors. All consecutive granulocyte donors from 1994 to 2012 were identified through our registry. From the donation records, the number of aphereses, stimulation therapy, AE, blood values post donation, and recent status were evaluated. One hundred fifty-four volunteer donors were mobilized for 359 collections. Age at first granulocyte donation was 43 years (median; range 19-64 years). Follow-up was 60 months (median; range 0-229 months). The dose of G-CSF per collection was 3.8 ug/kg body weight (median; range 1.6-6.0 ug/kg). Sedimentation agent was HES. Short-term AE were mild. Blood values 4 weeks post donation with minor reductions/elevations mostly resolved in later donations. Fourteen donors were excluded from the registry due to hypertension (4), diabetes (2), atrial flutter (1), breast carcinoma (1), urethral carcinoma in situ (1), MGUS (1), thrombosis (1), anaphylaxis (1), primary biliary cirrhosis (1), and unknown (1). Three donors are deceased due to diabetes, acute myocardial infarction, and unknown cause. All excluded/deceased donors except one were excluded/died at least 6 months after first granulocyte donation. No serious short-term AE were observed. Due to the variability of diagnoses among excluded/deceased donors, we propose that it is less likely that granulocyte donations have a causative impact on these donors' exclusion or death. © 2014 Wiley Periodicals, Inc.

Graft failure following bone marrow transplantation for severe aplastic anemia risk factors and treatment results

NARCIS (Netherlands)

Champlin, R.E.; Horowitz, M.M.; Bekkum, D.W. van; Camitta, B.M. Elfenbein, G.E.; Gale, R.P.; Gluckman, E.; Good, R.A.; Rimm, A.A. Rozman, C.; Speck, B. Bortin, M.M

1989-01-01

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in

Attention deficit hyperactivity disorder symptom severity and sleep problems in adult participants of the Netherlands sleep registry

NARCIS (Netherlands)

Vogel, Suzan W N; Bijlenga, Denise; Benjamins, Jeroen S; Beekman, Aartjan T F; Kooij, J J Sandra; Van Someren, Eus J W

2017-01-01

BACKGROUND: We examined whether current overall attention deficit hyperactivity disorder (ADHD), inattention, or hyperactivity symptom severities are associated with the current presence and persistent history of sleep problems. METHODS: N = 942 participants of the Netherlands Sleep Registry filled

Attention deficit hyperactivity disorder symptom severity and sleep problems in adult participants of the Netherlands sleep registry

NARCIS (Netherlands)

Vogel, Suzan W.N.; Bijlenga, Denise; Benjamins, Jeroen S.; Beekman, Aartjan T.F.; Kooij, J. J.Sandra; Van Someren, Eus J W

2017-01-01

Background We examined whether current overall attention deficit hyperactivity disorder (ADHD), inattention, or hyperactivity symptom severities are associated with the current presence and persistent history of sleep problems. Methods N = 942 participants of the Netherlands Sleep Registry filled

Successful bone marrow transplantation in sensitized recipients

International Nuclear Information System (INIS)

Levey, R.H.; Parkman, J.; Rappeport, J.; Nathan, D.G.; Rosen, F.

1979-01-01

Fourteen patients with aplastic anemia and one with the Wiskott-Aldrich syndrome who were specifically sensitized against their donors were successfully engrafted with bone marrow from those donors. Sensitivity was detected in antibody-independent and antibody-dependent cell-mediated lysis assays. In order to erase this immunity to non-MHR familial transplantation antigens, multiagent immunosuppression with cyclophosphamide, procarbazine, and whole rabbit antithymocyte serum (ATS) was used. The data suggest that ATS was largely responsible for abrogation of this sensitivity and indicate that immunity does not represent a barrier to successful transplantation

A qualitative study of blood and marrow transplant patient experiences participating in art making and music listening.

Science.gov (United States)

Mische Lawson, Lisa; Wedan, Lindsay; Stock, Morgan; Glennon, Cathy

2016-06-01

To explore patient experiences of engaging in art making or music listening while receiving treatment in a blood and marrow transplant clinic. Researchers recruited 25 individuals receiving blood and marrow transplant (BMT) treatment, 12 men and 13 women aged 22 to 74, from a Midwestern outpatient BMT clinic. Participants engaged in a painting activity or listened to music on an iPad using an internet music application for one hour. Researchers interviewed participants after the one-hour activity to gain insight into participants' perceptions of the art making or music listening experience. Interviews were recorded, transcribed verbatim, and independently coded by members of the research team. Researchers met on several occasions to analyse codes and agree on emerging themes. Nine themes emerged from the data including, Engaging in Activity, Art and Music in Daily Life, Expression, Engaging with Equipment, Novelty, BMT Process, Activity Process, Social Support, and Living Situation. Participants enjoyed art making and music listening and found the activities beneficial during treatment. Participants benefited from art making and music listening because these activities increased the variety of options available during treatment, allowed for self-expression, and could be done alone or with caregivers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Donor, dad, or…? Young adults with lesbian parents' experiences with known donors.

Science.gov (United States)

Goldberg, Abbie E; Allen, Katherine R

2013-06-01

In this exploratory qualitative study of 11 young adults, ages 19-29 years, we examine how young people who were raised by lesbian parents make meaning out of and construct their relationships with known donors. In-depth interviews were conducted to examine how participants defined their family composition, how they perceived the role of their donors in their lives, and how they negotiated their relationships with their donors. Findings indicate that mothers typically chose known donors who were family friends, that the majority of participants always knew who their donors were, and that their contact with donors ranged from minimal to involved. Further, participants perceived their donors in one of three ways: as strictly donors and not members of their family; as extended family members but not as parents; and as fathers. The more limited role of donors in participants' construction of family relationships sheds light on how children raised in lesbian, gay, and bisexual families are contributing to the redefinition and reconstruction of complex kinship arrangements. Our findings hold implications for clinicians who work with lesbian-mother families, and suggest that young adulthood is an important developmental phase during which interest in and contact with the donor may shift, warranting a transfer of responsibility from mother to offspring in terms of managing the donor-child relationship. © FPI, Inc.

Bone marrow transplantation for patients with chronic myeloid leukemia

International Nuclear Information System (INIS)

Goldman, J.M.; Apperley, J.F.; Jones, L.

1986-01-01

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72%, and the actuarial risk of relapse was 7%. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18%, and the actuarial risk of relapse was 42%. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established

Recruitment of feces donors among blood donors

DEFF Research Database (Denmark)

Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

2018-01-01

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

Science.gov (United States)

2018-02-28

Program HHQ Health History Questionnaire National Marrow Donor Program® N00014-16-1-2020 Development of Medical Technology for Contingency Response to...Report 3. DATES COVERED (From - To) DEC 2015 -November 2017 4. TITLE AND SUBTITLE Development of Medical Technology for Contingency Response to Marrow...immunobiologic and clinical research activities promote studies to advance the science and technology of HCT to improve outcomes and quality of life for

Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism

Directory of Open Access Journals (Sweden)

Rahul Pawar

2014-01-01

Full Text Available Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and skin biopsy showed large cell transformation. She was treated with multiple cycles of chemotherapy. Posttherapy PET scan showed resolution of lymphadenopathy. Later she underwent ablative preparative regimen followed by single cord blood transplant. Bone marrow chimerism studies at day +60 after transplant showed 100% donor cells without presence of lymphoma. However 5 months after transplant she had recurrence of MF with the same genotype as prior skin lesion. Bone marrow chimerism study continued to show 100% donor cells. Conclusion. A differential graft-versus-lymphoma effect in our case prevented lymphoma recurrence systemically but failed to do so in skin. We hypothesize that this response may be due to presence of other factors in the bone marrow and lymph node microenvironments preventing recurrence in these sites.

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Science.gov (United States)

Müller, Antonia M. S.; Poyser, Jessica; Küpper, Natascha J.; Burnett, Cassandra; Ko, Rose M.; Kohrt, Holbrook E.K.; Florek, Mareike; Zhang, Pei; Negrin, Robert S.

2014-01-01

Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique regimen that prepares recipients for allogeneic hematopoietic cell transplantation by targeting lymph nodes, while sparing large areas of the bone marrow. TLI is reported to increase the frequency of CD4+CD25+FoxP3+ T-regulatory cells (Treg) relative to conventional T cells. In this study, barriers to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but endogenous host HSC remained. Initial donor HSC engraftment occurred only in radiation exposed marrow sites, but gradually distributed to bone marrow outside the radiation field. Sustained donor engraftment required host lymphoid cells insofar as lymphocyte deficient Rag2γc−/− recipients had unstable engraftment compared with wild-type. TLI/ATG treated wild-type recipients had increased proportions of Treg that were associated with increased HSC frequency and proliferation. In contrast, Rag2γc−/− recipients who lacked Treg did not. Adoptive transfer of Treg into Rag2γc−/− recipients resulted in increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby promoting the exit of host HSC from the marrow niche. Our study highlights the unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg on HSC activity. PMID:24591203

The National Kidney Registry: 175 transplants in one year.

Science.gov (United States)

Veale, Jeffrey; Hil, Garet

2011-01-01

Since organizing its first swap in 2008, the National Kidney Registry had facilitated 389 kidney transplants by the end of 2011 across 45 U.S. transplant centers. Rapid innovations, advanced computer technologies, and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 94% as a result of improvements in the HLA typing process for donor antigens and enhanced mechanisms to list unacceptable HLA antigens for sensitized patients. By the end of 2011, the NKR had transplanted 66% of the patients enrolled since 2008. The 2011 wait time (from enrollment to transplant) for the 175 patients transplanted that year averaged 5 months.

Cancer Incidence and Mortality in a Cohort of US Blood Donors: A 20-Year Study

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Hirschler, Nora V.; Chinn, Artina; Busch, Michael P.; Custer, Brian

2013-01-01

Blood donors are considered one of the healthiest populations. This study describes the epidemiology of cancer in a cohort of blood donors up to 20 years after blood donation. Records from donors who participated in the Retroviral Epidemiology Donor Study (REDS, 1991–2002) at Blood Centers of the Pacific (BCP), San Francisco, were linked to the California Cancer Registry (CCR, 1991–2010). Standardized incidence ratios (SIR) were estimated using standard US 2000 population, and survival analysis used to compare all-cause mortality among donors and a random sample of nondonors with cancer from CCR. Of 55,158 eligible allogeneic blood donors followed-up for 863,902 person-years, 4,236 (7.7%) primary malignant cancers were diagnosed. SIR in donors was 1.59 (95% CI = 1.54,1.64). Donors had significantly lower mortality (adjusted HR = 0.70, 95% CI = 0.66–0.74) compared with nondonor cancer patients, except for respiratory system cancers (adjusted HR = 0.93, 95% CI = 0.82–1.05). Elevated cancer incidence among blood donors may reflect higher diagnosis rates due to health seeking behavior and cancer screening in donors. A “healthy donor effect” on mortality following cancer diagnosis was demonstrated. This population-based database and sample repository of blood donors with long-term monitoring of cancer incidence provides the opportunity for future analyses of genetic and other biomarkers of cancer. PMID:24489545

Cancer Incidence and Mortality in a Cohort of US Blood Donors: A 20-Year Study

Directory of Open Access Journals (Sweden)

Farnaz Vahidnia

2013-01-01

Full Text Available Blood donors are considered one of the healthiest populations. This study describes the epidemiology of cancer in a cohort of blood donors up to 20 years after blood donation. Records from donors who participated in the Retroviral Epidemiology Donor Study (REDS, 1991–2002 at Blood Centers of the Pacific (BCP, San Francisco, were linked to the California Cancer Registry (CCR, 1991–2010. Standardized incidence ratios (SIR were estimated using standard US 2000 population, and survival analysis used to compare all-cause mortality among donors and a random sample of nondonors with cancer from CCR. Of 55,158 eligible allogeneic blood donors followed-up for 863,902 person-years, 4,236 (7.7% primary malignant cancers were diagnosed. SIR in donors was 1.59 (95% CI = 1.54,1.64. Donors had significantly lower mortality (adjusted HR = 0.70, 95% CI = 0.66–0.74 compared with nondonor cancer patients, except for respiratory system cancers (adjusted HR = 0.93, 95% CI = 0.82–1.05. Elevated cancer incidence among blood donors may reflect higher diagnosis rates due to health seeking behavior and cancer screening in donors. A “healthy donor effect” on mortality following cancer diagnosis was demonstrated. This population-based database and sample repository of blood donors with long-term monitoring of cancer incidence provides the opportunity for future analyses of genetic and other biomarkers of cancer.

Bone marrow transplantation and other treatment after radiation injury

International Nuclear Information System (INIS)

Balner, H.

1977-01-01

This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

Overview of marrow transplantation

International Nuclear Information System (INIS)

Thomas, E.D.

1985-01-01

Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

Impact of starting material (fresh versus cryopreserved marrow) on mesenchymal stem cell culture.

Science.gov (United States)

Kaplan, Alesia; Sackett, Katie; Sumstad, Darin; Kadidlo, Dianne; McKenna, David H

2017-09-01

Mesenchymal stem cells (MSCs) continue to be investigated in multiple clinical trials as potential therapy for different disorders. There is ongoing controversy surrounding the clinical use of cryopreserved versus fresh MSCs. However, little is known about how cryopreservation affects marrow as starting material. The growth kinetics of MSC cultures derived from fresh versus cryopreserved marrow were compared. Data were reviewed on the growth kinetics of MSCs derived from fresh versus cryopreserved marrow of nine donors. Marrow harvested from each donor was separated into four aliquots (one fresh and three cryopreserved for culture). Data on the date of mononuclear cell cryopreservation/thaw, MSC counts at Passages 1 and 2, MSC doubling, MSC fold expansion, viability (of mononuclear cells and final MSCs), and on flow cytometry markers of mononuclear cells and final MSCs were analyzed for the fresh and cryopreserved marrow groups. In total, 21 MSC lots (seven fresh and 14 cryopreserved) were obtained. The average age of cryopreserved mononuclear cell product was 295 days (range, 18-1241 days). There were no significant differences between MSC numbers at Passage 1 (p = 0.1), final MSC numbers (p = 0.5), MSC doubling (p = 0.7), or MSC fold expansion (p = 0.7). A significant difference was observed in viability by flow cytometry for both mononuclear cells (p = 0.002) and final MSCs (p = 0.009), with higher viability in the fresh marrow group. This study demonstrates that MSCs derived from cryopreserved marrow have the same growth characteristics as fresh marrow-derived MSCs. Further studies are needed to explore potential differences in clinical efficacy. © 2017 AABB.

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

Science.gov (United States)

Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

2018-01-01

60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

Identifying specific non-attending groups in breast cancer screening - population-based registry study of participation and socio-demography

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Jensen Line

2012-11-01

Full Text Available Abstract Background A population-based breast cancer screening programme was implemented in the Central Denmark Region in 2008–09. The objective of this registry-based study was to examine the association between socio-demographic characteristics and screening participation and to examine whether the group of non-participants can be regarded as a homogeneous group of women. Method Participation status was obtained from a regional database for all women invited to the first screening round in the Central Denmark Region in 2008–2009 (n=149,234. Participation data was linked to registries containing socio-demographic information. Distance to screening site was calculated using ArcGIS. Participation was divided into ‘participants’ and ‘non-participants’, and non-participants were further stratified into ‘active non-participants’ and ‘passive non-participants’ based on whether the woman called and cancelled her participation or was a ‘no-show’. Results The screening participation rate was 78.9%. In multivariate analyses, non-participation was associated with older age, immigrant status, low OECD-adjusted household income, high and low level education compared with middle level education, unemployment, being unmarried, distance to screening site >20 km, being a tenant and no access to a vehicle. Active and passive non-participants comprised two distinct groups with different socio-demographic characteristics, with passive non-participants being more socially deprived compared with active non-participants. Conclusion Non-participation was associated with low social status e.g. low income, unemployment, no access to vehicle and status as tenant. Non-participants were also more likely than participants to be older, single, and of non-Danish origin. Compared to active non-participants, passive non-participants were characterized by e.g. lower income and lower educational level. Different interventions might be warranted to increase

Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

International Nuclear Information System (INIS)

Nakamura, H.; Gress, R.E.

1990-01-01

Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

Mechanism of stimulation of antibody-forming ability of bone marrow cells of mice immunized with staphylococci

International Nuclear Information System (INIS)

Lyashchenko, K.P.; Golovanova, T.A.; Bobrovnik, S.A.

1987-01-01

The purpose of this paper is to study the formation of the ability of the bone marrow cells of mice immunized with staphylococci to create antibodies to this antigen. The research includes a study of the effect of the irradiation in vitro of the bone marrow cells on their stimulating activity and the role played by the thymus and spleen in the formation of this activity. Experiments were carried out on CBA and BALB/c mice as well as on mice with congenital absence of the thymus. The bone marrow cell donors were immunized intravenously with staphylococcal corpuscular antigen. Receptor mice were irradiated with cobalt 60 gamma radiation and injected intravenously with bone marrow cell extract from the immunized donors and were immunized with the antigen. Spleen cells were labelled with chromium 51 and injected intravenously into intact syngeneic recipients together with as well as without the antigen. Three days later the level of radioactivity in the spleen and femora of the animals was determined by scintillation counting. Total radioactivity of the bone marrow was calculated. Irradiation of the bone marrow cells of immunized animals was shown to abolish their stimulating effect on the humoral immune response of intact syngeneic recipients to the staphylococcal corpuscular antigen. Consequently, the immunostimulating effect of bone marrow cells is realized through the proliferating and radiosensitive lymphoid cells rather than through the macrophages

Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita.

Science.gov (United States)

Nishio, Nobuhiro; Takahashi, Yoshiyuki; Ohashi, Haruhiko; Doisaki, Sayoko; Muramatsu, Hideki; Hama, Asahito; Shimada, Akira; Yagasaki, Hiroshi; Kojima, Seiji

2011-03-01

DC is an inherited bone marrow failure syndrome mainly characterized by nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure is the most common cause of death in patients with DC. Because previous results of HSCT with a myeloablative regimen were disappointing, we used a reduced-intensity conditioning regimen for two patients with classic DC, and one patient with cryptic DC who harbored the TERT mutation. Graft sources included two mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful engraftment was achieved with few regimen-related toxicities in all patients. They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen. © 2010 John Wiley & Sons A/S.

Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

NARCIS (Netherlands)

Lokhorst, H. M.; Lamme, T.; de Smet, M.; Klein, S.; de Weger, R. A.; van Oers, R.; Bloem, A. C.

1994-01-01

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Science.gov (United States)

Sharon, Eilon; Shi, Hao; Kharbanda, Sandhya; Koh, Winston; Martin, Lance R; Khush, Kiran K; Valantine, Hannah; Pritchard, Jonathan K; De Vlaminck, Iwijn

2017-08-01

Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

International Nuclear Information System (INIS)

Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

1991-01-01

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

Directory of Open Access Journals (Sweden)

Christopher A Smith

Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

Reasons for (not) signing the state registry: surveying Department of Motor Vehicles customers in New York state.

Science.gov (United States)

Feeley, Thomas Hugh; Reynolds-Tylus, Tobias; Anker, Ashley E; Evans, Melanie

2014-03-01

Prior research examining rationales for enrolling as an organ donor is biased because of its reliance on college student samples and retrospective recall. To characterize New York state residents' registry enrollment decisions in close proximity to a registration opportunity. -Surveys were conducted with customers exiting Department of Motor Vehicle offices. A total of 1325 customers were surveyed upon exiting 1 of 18 Department of Motor Vehicle offices spanning 9 counties. Customers making donation-relevant transactions (ie, license renewal/registration) reported whether they had registered as a donor that day, and all other customers reported whether they had registered as a donor in the past. Customers reported reasons to justify their enrollment decision through short interview questions. Among current donation-relevant transactions (n = 299), 27% reported enrolling in the registry. Of remaining customers, 39% reported enrolling in the state registry in the past. For those who elected not to enroll, many failed to communicate a reason for their decision, or reported a lack of opportunity to sign or decisional uncertainty. Among enrollees, reasons for registration included the altruistic benefits of donation, prior registration, personal experience with donation, and rational arguments for donation. The value of point-of-decision survey data are discussed in relation to strategic efforts to promote organ donor registration.

Mechanism of donor to host tolerance in rat bone marrow chimeras

International Nuclear Information System (INIS)

Tutschka, P.; Schwerdtfeger, R.; Slavin, R.; Santos, G.

1977-01-01

Lewis rats were conditioned with cyclophosphamide and grafted with AgB incompatible bone marrow. They were examined 250 days after transplantation and demonstrated to be healthy complete chimeras. Marrow cells from these chimeras were infused into lethally irradiated ACI, Lewis and BN recipients. Graft-versus-host disease occurred only in the BN rats. Other chimeric rats were given no treatment, busulfan, CY, or total body irradiation prior to the infusion of normal ACI BM. GvHD occurred only in animals given CY or TBI. Normal Lewis rats were conditioned with TBI and given ACI BM. In addition, they received whole blood, irradiated blood, or serum from chimeric rats. GvHD developed in all animals except those given unirradiated chimeric blood. These studies suggest that suppressor cell populations, sensitive to immunosuppression, are likely the fundamental mechanism of recovery from GvHD

Influence of intensity of bone marrow erythropoietic activity on radiosensitivity of mice

International Nuclear Information System (INIS)

Kwiek, S. Jr.

1985-01-01

Hypererythropoiesis was induced in mice by exposure to carbon monoxide. They became polycythemic after transfer to normal air. Mice irradiated with 550-650 R of X-rays in the state of polycythemia had higher 30-day survival than controls. Bone marrow levels of multipotential haemopoietic stem cells (CFU-S) were found to be elevated by 50% in polycythemic mice and after whole body sublethal irradiation (200 R) substantially faster regeneration of bone marrow was noted in them. It was estimated by renewal of bone marrow cellularity, content of CFU-S and ability to growth in diffusion chambers. Bone marrow from polycythemic mice was found to yield considerably less macrophages than the ones from hypererythropoietic and normal donors. 27 refs., 5 tabs. (author)

Gillick, bone marrow and teenagers.

Science.gov (United States)

Cherkassky, Lisa

2015-09-01

The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.1 of the Children Act 1989? There are no legal authorities on child bone marrow harvests in the United Kingdom. This article considers the best interests of the older saviour sibling and questions whether, for the purposes of welfare, the speculative benefits could outweigh the physical burdens. © The Author(s) 2015.

Engraftment of allogeneic bone marrow without graft-versus-host disease in mongrel dogs using total lymphoid irradiation

International Nuclear Information System (INIS)

Gottlieb, M.; Strober, S.; Hoppe, R.T.; Grumet, F.C.; Kaplan, H.S.

1980-01-01

We achieved long-term engraftment of unmatched bone marrow (BM) in dogs without graft-versus-host disease (GVHD) using a regimen of total lymphoid irradiation (TLI) which could be applied clinically. Twelve normal adult mongrel dogs were given TLI in 18 fractions of 100 rad each (total dose, 1800 rad) over 4 weeks to mantle and abdominal fields in continuity. Nine of the 12 were transfused with one or two random donor whole blood transfusions during the irradiation regimen to determine the risk of sensitization after the onset of immunosuppression. A mean (+- SD) of 0.71 +- 0.54 x 10 9 BM cells/kg of recipient body weight from unrelated sex-mismatched donors was infused within 24 h of the 18th irradiation fraction. Engraftment was assessed by demonstration of donor-type sex chromosomes in spontaneous metaphase spreads of recipient marrow aspirates, and by the appearance of donor-type red blood cells antigens (DEA) in the recipients' blood. Three untransfused and nine transfused recipients were shown to be stable mixed BM chimeras during a followup period of 2 to 11 months after transplantation. Blood transfusion during TLI did not result in graft rejection. We observed no clinical signs of acute or chronic GVHD. TLI has minimal toxicity when compared with conditioning regimens currently used in BM transplantation for aplastic anemia. Potential advantages of the TLI regimen include the opportunity to use unmatched marrow donors and protection from GVHD

[Information and consent forms for hematopoietic stem cell transplantation donors and recipients: Guidelines from the Franchophone society of bone marrow transplantation and cellular therapy (SFGM-TC)].

Science.gov (United States)

Bruno, Bénédicte; Thibert, Jean-Baptiste; Bancillon, Nelly; Desbos, Anna; Fawaz, Abir; Fournier, Isabelle; Genty, Carole; Issarni, Dominique; Leveille, Sandrine; Premel, Christelle; Polomeni, Alice; Renault, Myriam; Tarillon, Sylvie; Wallart, Anne; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

2016-11-01

Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Directory of Open Access Journals (Sweden)

Eilon Sharon

2017-08-01

Full Text Available Quantification of cell-free DNA (cfDNA in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD quantifies donor-derived cfDNA (dd-cfDNA by taking advantage of single-nucleotide polymorphisms (SNPs distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM of identity-by-descent (IBD states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD. These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

Participating in an International Stereotactic Radiotherapy Patient Registry: The Establishment of Data Collection Pathways.

Science.gov (United States)

Yahya, Aylin; Arneric, Eva; Kernutt, Elizabeth; Baldacchino, Fiona; Haworth, Claire; Kedda, Mary-Anne; Tang, Colin; Bydder, Sean; Corica, Tammy

2017-06-29

Aim To describe data collection pathways and practical challenges experienced by an academic comprehensive cancer centre aiming to record clinical data for patients being treated with a novel radiotherapy treatment modality. Methods Various options to capture data from all patients treated with the CyberKnife Robotic Radiosurgery System at Sir Charles Gairdner Hospital (SCGH) in Western Australia were explored. An international multicenter web-based secure database established and maintained by the Radiosurgery Society the RSSearch® Patient Registry was selected. Data were collected and entered over four contiguous phases, with either opt-in or opt-out consent and the completion of Patient Reported Outcome questionnaires for specific sub-groups. Results Between April 2014 and June 2016, 461 patients at Sir Charles Gairdner Hospital were enrolled in the RSSearch® Patient Registry with the collection of over 17,500 data items. From 461 patients enrolled, 447 patients were treated with the CyberKnife Robotic Radiosurgery System. The majority of patients were treated for either a malignant primary (43.2%) or metastatic disease (39.4%). The establishment of matrix organisational processes for data collection led to the development of improved workflow patterns and data collection pathways. Conclusions This article describes the processes developed by a single centre to establish an efficient system for data collection and participation in an international registry. The opt-out approach was more efficient in terms of patient recruitment compared to the informed-consent method used in earlier phases. The experience of this single centre may help inform other institutions considering data collection options for assessments of new or novel treatments.

Quarterly Performance/Technical Report of the National Marrow Donor Program

National Research Council Canada - National Science Library

Setterholm, Michelle

2009-01-01

... a nationwide contingency response plan. Rapid Identification of Matched Donors: Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event...

Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells

Directory of Open Access Journals (Sweden)

Thomas Bart

2010-10-01

Full Text Available Thomas BartSwiss Blood Stem Cells, Bern, SwitzerlandAbstract: Umbilical cord blood (CB has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT is given. The three main sources of hematopoietic stem cells: bone marrow (BM, peripheral blood stem cells (PBSC, and cord blood (CB are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.Keywords: health economy, cord blood, hematopoietic stem cell transplantation

Evaluating the Efficacy of a Registry linked to a Consent to Re-Contact Program and Communication Strategies for Recruiting and Enrolling Participants into Clinical Trials.

Science.gov (United States)

Flood-Grady, Elizabeth; Clark, Virginia C; Bauer, Angie; Morelli, Lauren; Horne, Patrick; Krieger, Janice L; Nelson, David R

2017-12-01

Although registries can rapidly identify clinical study participants, it is unknown which follow up methods for recruiting are most effective. Our goal is to examine the efficacy of three communication strategies for recruiting and enrolling patients who were identified via a contact registry (i.e., registry linked to a consent to re-contact program). Patients who met the study criteria were identified via the contact registry and targeted for recruitment. In condition 1, patients established in the university hepatology specialty clinics were contacted one time via phone call by the study coordinator and asked to participate (C1). In condition 2, non-established specialty clinic patients were mailed an IRB-approved letter with study information and instructions for calling the study coordinator to participate (C2). Condition 2A included patients who called within two weeks of receiving the letter (C2A); condition 2B included patients who did not call after receiving the letter but were subsequently contacted via phone call. A registry identified 1,060 patients, of which 661were eligible and targeted for recruiting. All 37 patients were reached in C1 and 17 (45.9%) were recruited. Nineteen of the 624 patients in C2A were reached and 10 were recruited whereas 120 of the 605 patients in C2B were reached and 53 (8.7%) were recruited. Seventy patients enrolled with C2B being the most effective (total, cost) recruitment strategy ( n = 50) ( p recruiting.

Quarterly Performance/Technical Report of the National Marrow Donor Program

National Research Council Canada - National Science Library

Coppo, Patrica A; Davis, Judy W; Spellman, Steve M

2006-01-01

... a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event...

Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells

International Nuclear Information System (INIS)

Britt, L.D.; Scharp, D.W.; Lacy, P.E.; Slavin, S.

1982-01-01

Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression

Development of a "Myeloma Risk Score" using a population-based registry on paraproteinemia and myeloma

NARCIS (Netherlands)

Ong, F; Hermans, J; Noordijk, E M; De Kieviet, W; Seelen, P J; Wijermans, P W; Kluin-Nelemans, J C

1997-01-01

Diagnostic systems for monoclonal gammopathies use bone marrow and X-ray examinations to exclude multiple myeloma (MM). Data from a population-based registry of unselected patients with paraproteinemia indicate that these tests are often done only when MM is suspected. We used 441 randomly selected

Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester

International Nuclear Information System (INIS)

Charley, M.; Thiele, D.L.; Bennett, M.; Lipsky, P.E.

1986-01-01

Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 microM Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 microM Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2'-deoxyuridine- 125 I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

Science.gov (United States)

Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

2015-04-01

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD. © 2014 John Wiley & Sons Ltd.

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

Science.gov (United States)

Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

2015-09-01

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of host lymphoid cells in antibody-facilitated bone marrow chimeras

International Nuclear Information System (INIS)

McCarthy, S.A.; Griffith, I.J.; Gambel, P.; Francescutti, L.H.; Wegmann, T.G.

1985-01-01

The authors have produced stable murine antibody-facilitated (AF) chimeras by the simultaneous injection of P1 bone marrow cells and anti-P2 monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These AF chimeras are healthy, long-lived, and exhibit no overt signs of graft-versus-host disease. They are immunocompetent and tolerant of host, P2-encoded alloantigens. Donor cell engraftment and takeover, monitored by glucosephosphate isomerase isozyme patterns, is usually complete (greater than 95%) in the peripheral blood, bone marrow, and hemopoietic stem cell compartments of long-term (greater than 3 months posttransplantation) AF chimeras. The authors report here, however, that splenic, lymph node, and thymic leukocytes of AF chimeras represent donor/host chimeric populations. Spleen cell populations of AF chimeras exhibit substantial chimera-to-chimera variation in the preponderant residual host cell type(s) present. Interpretations of the implications of these findings are discussed

The Impact of Total Ischemic Time, Donor Age and the Pathway of Donor Death on Graft Outcomes After Deceased Donor Kidney Transplantation.

Science.gov (United States)

Wong, Germaine; Teixeira-Pinto, Armando; Chapman, Jeremy R; Craig, Jonathan C; Pleass, Henry; McDonald, Stephen; Lim, Wai H

2017-06-01

Prolonged ischemia is a known risk factor for delayed graft function (DGF) and its interaction with donor characteristics, the pathways of donor death, and graft outcomes may have important implications for allocation policies. Using data from the Australian and New Zealand Dialysis and Transplant registry (1994-2013), we examined the relationship between total ischemic time with graft outcomes among recipients who received their first deceased donor kidney transplants. Total ischemic time (in hours) was defined as the time of the donor renal artery interruption or aortic clamp, until the time of release of the clamp on the renal artery in the recipient. A total of 7542 recipients were followed up over a median follow-up time of 5.3 years (interquartile range of 8.2 years). Of these, 1823 (24.6%) experienced DGF and 2553 (33.9%) experienced allograft loss. Recipients with total ischemic time of 14 hours or longer experienced an increased odd of DGF compared with those with total ischemic time less than 14 hours. This effect was most marked among those with older donors (P value for interaction = 0.01). There was a significant interaction between total ischemic time, donor age, and graft loss (P value for interaction = 0.03). There was on average, a 9% increase in the overall risk of graft loss per hour increase in the total ischemic time (adjusted hazard ratio, 1.09; 95% confidence interval, 1.01-1.18; P = 0.02) in recipients with older donation after circulatory death grafts. There is a clinically important interaction between donor age, the pathway of donor death, and total ischemic time on graft outcomes, such that the duration of ischemic time has the greatest impact on graft survival in recipients with older donation after circulatory death kidneys.

Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

International Nuclear Information System (INIS)

Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

1988-01-01

Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus

Simultaneous development of antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity in irradiated mice reconstituted with bone marrow cells

International Nuclear Information System (INIS)

Sihvola, M.; Hurme, M.

1987-01-01

Spleen cells from irradiated, bone marrow-reconstituted mice were tested for their ability to mediate antibody-dependent cellular cytotoxicity against P815 target (ADCC-P815), ADCC against sheep red blood cells (ADCC-SRBC), and natural killer (NK) activity judged as YAC-1 lysis at different times after bone marrow reconstitution. Donor-derived ADCC-P815 effectors were found to appear in the spleens 10-12 days after bone marrow reconstitution simultaneously with the appearance of donor-derived NK cells. NK cells recently derived from bone marrow are known to express the Thy-1 antigen; the phenotype of the ''early'' ADCC-P815 effectors was found to be the same as that of NK cells, i.e., Thy-1+, asialo-GM1+. These data suggest that ADCC-P815 effector cells belong to the NK cell population. ADCC-SRBC, in contrast to ADCC-P815 and NK activity, was already high on Day 7 after bone marrow reconstitution. However, it was mediated partly by recipient-derived effectors. ADCC-SRBC effectors were characterized to be different from ADCC-P815 effectors

The long and the short of telomeres in bone marrow recipient SCID patients.

Science.gov (United States)

Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G; Whitesides, John F; Buckley, Rebecca H

2011-04-01

Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant's vestigial thymus and to homeostatic proliferation of mature T cells in the peripheral organs. Since T-cell function, thymic output, and T-cell clonal diversity are maintained long term in these patients, we investigated whether donor T-cell engraftment resulted in increased telomere shortening. Our study of seven SCID patients, following successful bone marrow transplantation, demonstrates that the patients' peripheral T cells did not exhibit greater than normal telomere shortening.

HEMATOPOIETIC PROGENITOR CELL CONTENT OF VERTEBRAL BODY MARROW USED FOR COMBINED SOLID ORGAN AND BONE MARROW TRANSPLANTATION

Science.gov (United States)

Rybka, Witold B.; Fontes, Paulo A.; Rao, Abdul S.; Winkelstein, Alan; Ricordi, Camillo; Ball, Edward D.; Starzl, Thomas E.

2010-01-01

While cadaveric vertebral bodies (VB) have long been proposed as a suitable source of bone marrow (BM) for transplantation (BMT), they have rarely been used for this purpose. We have infused VB BM immediately following whole organ (WO) transplantation to augment donor cell chimerism. We quantified the hematopoietic progenitor cell (HPC) content of VB BM as well as BM obtained from the iliac crests (IC) of normal allogeneic donors (ALLO) and from patients with malignancy undergoing autologous marrow harvest (AUTO). Patients undergoing WOIBM transplantation also had AUTO BM harvested in the event that subsequent lymphohematopoietic reconstitution was required. Twenty-four VB BM, 24 IC BM-ALLO, 31 IC AUTO, and 24 IC WO-AUTO were harvested. VB BM was tested 12 to 72 hr after procurement and infused after completion ofWO grafting. IC BM was tested and then used or cryopreserved immediately. HPC were quantified by clonal assay measuring CFU-GM, BFU-E, and CFU-GEMM, and by flow cytometry for CD34+ progenitor cells. On an average, 9 VB were processed during each harvest, and despite an extended processing time the number of viable nucleated cells obtained was significantly higher than that from IC. Furthermore, by HPC content, VB BM was equivalent to IC BM, which is routinely used for BMT. We conclude that VB BM is a clinically valuable source of BM for allogeneic transplantation. PMID:7701582

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance.

Science.gov (United States)

de Swart, Louise; Smith, Alex; MacKenzie, Marius; Symeonidis, Argiris; Neukirchen, Judith; Mikulenková, Dana; Vallespí, Teresa; Zini, Gina; Paszkowska-Kowalewska, Malgorzata; Kruger, Anton; Saft, Leonie; Fenaux, Pierre; Bowen, David; Hellström-Lindberg, Eva; Čermák, Jaroslav; Stauder, Reinhard; Tatic, Aurelia; Holm, Mette Skov; Malcovati, Luca; Mądry, Krzysztof; Droste, Jackie; Blijlevens, Nicole; de Witte, Theo; Germing, Ulrich

2017-07-01

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

Thymic repopulation following intrathymic injection of mouse bone marrow cells in MHC matched and mismatched recipients

International Nuclear Information System (INIS)

Chervenak, R.

1986-01-01

T cell precursors (pre-T cells) have traditionally been detected by their ability to repopulate the thymus of heavily irradiated mice following intravenous injection. Recently, Goldschneider et. al. developed an assay system which involves the direct injection of pre-T cells into the thymus. The authors used this technique to evaluate the ability of bone marrow cells to repopulate thymuses in various donor-host strain combinations. Sub-lethally irradiated (600R) mice were injected intrathymically with 2 x 10 6 bone marrow cells which differed from the recipient with respect to their Thy 1 allotype. The percentage of thymus cells expressing either the donor or recipient type Thy 1 marker was determined 14 to 21 days after injection. These experiments showed that in MHC matched donor-host combinations (AKR/cum → AKR/J and CBA/J → AKR/J), cells derived from the donor inoculum accounted for 40% to 75% of the total thymus population. MHC mismatched donor-host combinations (C57BL/6J → AKR/J and Balb/c → AKR/J) resulted in significantly less donor-type repopulation of the thymus. In these cases, donor repopulation typically ranged from 0% to 4%. The ability of the pre-T cells detected by intrathymic injection to proliferate in the thymic environment, therefore, appears to be influenced by the MHC. This may reflect commitment of pre-T cells to MHC haplotype recognition prior to their migration to the thymus

Living related donor liver transplantation.

Science.gov (United States)

Chen, C L; Chen, Y S; Liu, P P; Chiang, Y C; Cheng, Y F; Huang, T L; Eng, H L

1997-10-01

Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra-operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra-operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n = 10) and glycogen storage disease (n = 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.

Bone marrow transplantation for acute myelogenous leukemia: factors associated with early mortality

International Nuclear Information System (INIS)

Bortin, M.M.; Gale, R.P.; Kay, H.E.; Rimm, A.A.

1983-01-01

Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells.It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid Leukemia.

Science.gov (United States)

Elmariah, Hany; Pratz, Keith W

2017-07-01

Adult acute myeloid leukemia (AML) is often associated with a poor prognosis, with allogeneic transplantation representing the greatest chance of cure for eligible patients. Historically, the preferred donor source is a human leukocyte antigen-matched blood relative, although only approximately 30% of patients have access to such a donor. Alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical related donors, are available for almost every patient and are increasingly being used for patients without a matched related donor. Survival outcomes with these alternative donor sources now approximate those of matched related donor transplants. Given the safety and success of alternative donor transplants, comparative trials are needed to reassess the optimal donor source for patients with AML. This review summarizes the available data on these alternative donor transplants. Further investigation is needed to contemporize donor selection algorithms, but, in the current era, donor availability should no longer preclude a patient's eligibility for an allogeneic blood or marrow transplant. Copyright © 2017 by the National Comprehensive Cancer Network.

[Favorable current prognosis after HLA-identical bone marrow transplantation for children with required severe aplastic anemia; evaluation of 30 years of bone marrow transplantation at the Leiden University Medical Center

NARCIS (Netherlands)

Steekelenburg, M. van; Weel-Sipman, M.H. van; Zwinderman, A.H.; Hoogerbrugge, P.M.; Vossen, J.M.J.J.; Egeler, R.M.

2002-01-01

OBJECTIVE: To evaluate the results of 30 years of allogeneic HLA-identical bone marrow transplantation (BMT) as the treatment for children with acquired severe aplastic anaemia. DESIGN: Retrospective, descriptive. METHOD: Of all patients who underwent an HLA-identical sibling-donor BMT for severe

Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

Directory of Open Access Journals (Sweden)

Margarida Dantas Brito

2014-01-01

Full Text Available Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogeneic SCT was performed with peripheral blood stem cells from an unrelated Portuguese matched donor. In the following months, patient developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and 80∗109/L. The only significant complaint was intermittent tiredness. The common causes for thrombocytopenia in this setting were excluded—no evidence of graft versus host disease, no signs of viral or bacterial infection, and no signs of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months after transplantation revealed an unsuspected diagnosis: a massive bone marrow infiltration with amastigotes.

Brain donation in psychiatry: results of a Dutch prospective donor program among psychiatric cohort participants.

Science.gov (United States)

de Lange, Geertje M; Rademaker, Marleen; Boks, Marco P; Palmen, Saskia J M C

2017-10-20

Human brain tissue is crucial to study the molecular and cellular basis of psychiatric disorders. However, the current availability of human brain tissue is inadequate. Therefore, the Netherlands Brain Bank initiated a program in which almost 4.000 participants of 15 large Dutch psychiatric research cohorts were asked to register as prospective brain donors. We approached patients with schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, families with a child with autism or Attention Deficit Hyperactivity Disorder, healthy relatives and healthy unrelated controls, either face-to-face or by post. We investigated whether diagnosis, method of approach, age, and gender were related to the likelihood of brain-donor registration. We found a striking difference in registration efficiency between the diagnosis groups. Patients with bipolar disorder and healthy relatives registered most often (25% respectively 17%), followed by unrelated controls (8%) and patients with major depressive disorder, post-traumatic stress disorder, and obsessive-compulsive disorder (9%, 6% resp. 5%). A face-to-face approach was 1.3 times more effective than a postal approach and the likelihood of registering as brain donor significantly increased with age. Gender did not make a difference. Between 2013 and 2016, our prospective brain-donor program for psychiatry resulted in an almost eightfold increase (from 149 to 1149) in the number of registered psychiatric patients at the Netherlands Brain Bank. Based on our results we recommend, when starting a prospective brain donor program in psychiatric patients, to focus on face to face recruitment of people in their sixties or older.

Bone marrow transplantation in miniature swine: I. Autologous and SLA matched allografts

International Nuclear Information System (INIS)

Pennington, L.R.; Pescovitz, M.D.; Popitz, F.; Sachs, D.H.; Sakamoto, K.

1986-01-01

We developed a successful bone marrow transplant protocol in MHC-inbred miniature swine (MS). Three groups of MS were studied: irradiation controls, autologous bone marrow transplants and SLA matched bone marrow allografts. One day prior to irradiation, all animals underwent Hickman catheter placement via the external jugular vein. Bone marrow was harvested by direct mechanical removal of marrow from four long bones in Groups 2 and 3 one day prior to irradiation. All animals received 900 rads of midline body radiation from a Cobalt-60 source, were treated 1 g of cephalothin IV bid from day 1 to 14, 20 mg of genetamicin IV bid, from day 4 through 14 and 250 to 350 ml of fresh, irradiated whole blood from blood group identical donors on days 7, 11 and 14. Bone marrow was filtered, washed, stored overnight at 4 C and reinfused one to six hr after irradiation. Engraftment was defined by return of the peripheral WBC to 1000/mm 3 . All six animals in Group 1 died of aplasia between days 7 and 12. Marrow engrafted in eight of 12 animals in Group 2 and 7 of 10 animals in Group 3. This model provides a means to study the biological characteristics of bone marrow transplantation in immunologically well characterized large animals and should prove useful as a model for bone marrow transplants in man

Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry.

Science.gov (United States)

Patton, William Nigel; Nivison-Smith, Ian; Bardy, Peter; Dodds, Anthony; Ma, David; Shaw, Peter John; Kwan, John; Wilcox, Leonie; Butler, Andrew; Carter, John M; Blacklock, Hilary; Szer, Jeffrey

2017-01-01

A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A quality of life study in 20 adult long-term survivors of unrelated donor bone marrow transplantation.

Science.gov (United States)

Marks, D I; Gale, D J; Vedhara, K; Bird, J M

1999-07-01

There are few specific data available concerning quality of life (QOL) of survivors of unrelated donor bone marrow transplantation (UD-BMT). The procedure is expensive, difficult and is being employed increasingly yet we have little information concerning the QOL of survivors to justify this intervention. In this study, 20 long-term (>1 year post-BMT) survivors were studied with four self report questionnaires designed to assess quality of life, satisfaction with life, social support and employment status. Overall, satisfaction with life measures was above average but there was dissatisfaction with physical strength and appearance. The post-transplant employment data indicates that 60% of long-term survivors returned to full-time work and 15% to part-time work. Failure to return to work was not correlated with graft-versus-host disease (GVHD), relapse, age at or time since transplant. In general, there was a good correlation between the clinician's and patient's view of their health but the clinician's assessment of the patients mental health and energy was higher than the patients reported. Further research is required in the area of QOL post-UD-BMT. This will enable transplant physicians to counsel patients better pre-BMT and to evaluate fully the results achieved by different centres performing the procedure.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

Science.gov (United States)

Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

2009-09-01

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

Science.gov (United States)

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

The United States Transuranium and Uranium Registries: overview and recent progress

International Nuclear Information System (INIS)

Kathren, R.L.

1989-01-01

This paper describes the organisation, activities and recent scientific accomplishments of the United States Transuranium and Uranium Registries. Through voluntary donations of tissue obtained at autopsies, the Registries carry out studies of the concentration, distribution and biokinetics of actinides in occupationally exposed persons. Findings from tissue analyses from more than 200 autopsies include the following: a greater proportion of the americium intake, as compared with plutonium, is found in the skeleton; the half-time of americium in liver is significantly shorter than that of plutonium; the concentration of actinide in the skeleton is inversely proportional to the calcium and ash content of the bone; only a small percentage of the total skeletal deposition of plutonium is found in the marrow, implying a smaller risk from irradiation of the marrow relative to the bone surfaces; estimates of plutonium body burden made from urinalysis typically exceed those made from autopsy data; pathologists are unable to discriminate between a group of uranium workers and persons without known occupational exposure on the basis of evaluation of microscopic kidney slides; the skeleton is an important long-term depot for uranium and its fractional uptake by both skeleton and kidney may be greater than indicated by current models. These and other findings and current studies are discussed in depth. (author)

Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

Science.gov (United States)

Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

1993-03-01

When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

Karyotype of cryopreserved bone marrow cells

Directory of Open Access Journals (Sweden)

M.L.L.F. Chauffaille

2003-07-01

Full Text Available The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis. Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05. Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05. GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

Karyotype of cryopreserved bone marrow cells.

Science.gov (United States)

Chauffaille, M L L F; Pinheiro, R F; Stefano, J T; Kerbauy, J

2003-07-01

The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases) to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis). Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively) were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05). Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05). GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

Ceramic hydroxyapatite coating on titanium implants drives selective bone marrow stromal cell adhesion.

NARCIS (Netherlands)

Torensma, R.; Brugge, P.J. ter; Jansen, J.A.; Figdor, C.G.

2003-01-01

The aim of this study was to determine the cell characteristics that regulate implant osseointegration. The heterogeneity of bone marrow stromal cells obtained from 11 donors was assessed by measuring the expression of a large panel of adhesion molecules. Large differences in expression of adhesion

Quarterly Performance/Technical Report of the National Marrow Donor Program (Trademark)

National Research Council Canada - National Science Library

Setterholm, Michelle

2008-01-01

... a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. 3...

Provocation of skin graft rejection across murine class II differences by non--bone-marrow-derived cells

International Nuclear Information System (INIS)

Stuart, P.M.; Beck-Maier, B.; Melvold, R.W.

1984-01-01

We have evaluated the relative contribution of bone-marrow-derived cells to skin allograft immunogenicity in mice differing only at class II major histocompatibility genes by using bone marrow radiation chimeras as donors. The mouse strains used were C57BL/6Kh (B6) and B6.C-H-2bm12 (bm12), which differ only at at A beta gene of the I region of the mouse H-2 complex. Our results demonstrated that skin from (B6----bm12) chimeras was accepted by bm12 recipients and rejected by B6 mice in a manner indistinguishable from that of normal bm12 skin. Likewise, naive bm12 mice rejected (bm12----B6) chimeric skin and normal B6 skin equally well, and B6 animals accepted both types of skin grafts. Our data argues that the donor cell-type leading to graft rejection across limited I region differences is not of bone marrow origin, and that these cells must--at least under certain circumstances--express class II antigens

The effect of variation in donor platelet function on transfusion outcome: a semirandomized controlled trial.

Science.gov (United States)

Kelly, Anne M; Garner, Stephen F; Foukaneli, Theodora; Godec, Thomas R; Herbert, Nina; Kahan, Brennan C; Deary, Alison; Bakrania, Lekha; Llewelyn, Charlotte; Ouwehand, Willem H; Williamson, Lorna M; Cardigan, Rebecca A

2017-07-13

The effect of variation in platelet function in platelet donors on patient outcome following platelet transfusion is unknown. This trial assessed the hypothesis that platelets collected from donors with highly responsive platelets to agonists in vitro assessed by flow cytometry (high-responder donors) are cleared more quickly from the circulation than those from low-responder donors, resulting in lower platelet count increments following transfusion. This parallel group, semirandomized double-blinded trial was conducted in a single center in the United Kingdom. Eligible patients were those 16 or older with thrombocytopenia secondary to bone marrow failure, requiring prophylactic platelet transfusion. Patients were randomly assigned to receive a platelet donation from a high- or low-responder donor when both were available, or when only 1 type of platelet was available, patients received that. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary end point was the platelet count increment 10 to 90 minutes following transfusion. Analysis was by intention to treat. Fifty-one patients were assigned to receive platelets from low-responder donors, and 49 from high-responder donors (47 of which were randomized and 53 nonrandomized). There was no significant difference in platelet count increment 10 to 90 minutes following transfusion in patients receiving platelets from high-responder (mean, 21.0 × 10 9 /L; 95% confidence interval [CI], 4.9-37.2) or low-responder (mean, 23.3 × 10 9 /L; 95% CI, 7.8-38.9) donors (mean difference, 2.3; 95% CI, -1.1 to 5.7; P = .18). These results support the current policy of not selecting platelet donors on the basis of platelet function for prophylactic platelet transfusion. © 2017 by The American Society of Hematology.

Transplantation of cryopreserved allogeneic bone marrow after its long-term storage to lethally irradiated dogs

International Nuclear Information System (INIS)

Novikova, N.N.; Fedotenkov, A.G.; Sukyasyan, G.V.; Timakova, L.A.

1982-01-01

The study of the dog bone marrow preserved at -196 deg C during 6-12 years has shown that in the body of lethally irradiated animals (8Gy), due to the antigenic difference in the tissues of the donor and the irradiated recipients, the cells of cryopreserved allogeneic bone marrow were differentiated by the lymphoid type similar to that observed in transplantation of freshly prepared myelocaryocytes. However, their proliferative activity in the period of active lymphocyte transformation was quantitatively less manifest than in freshly transplanted cells. The results of the study evidence that the bone marrow cells cryopreserved during 6-12 years retain their functional activity

Hemopoietic regeneration in murine spleen following transfusion of normal and irradiated marrow: different response of granulocyte/macrophage and erythroid precursors

International Nuclear Information System (INIS)

Wangenheim, K.-H. von; Peterson, H.-P.; Huebner, G.E.; Feinendegen, L.E.

1987-01-01

To investigate cell proliferation in regenerating spleen, bone marrow of normal and gamma-irradiated donor mice (3 weeks after 5 Gy) was transfused into lethally irradiated recipients. In the donors and in the recipient spleens numbers of CFU-S and progenitor cells were determined. In the irradiated donors the progenitors were at control level after 3 weeks of recovery although CFU-S were still at 50% of control. Recipients of the irradiated marrow received therefore an increased proportion of progenitors. CFU-C appeared to be self-renewing and/or increased in number due to enhanced CFU-S differentiation, but not the erythroid progenitors. CFU-S self-renewal was reduced after 5 Gy. The data suggest that cell differentiation and maturation proceed during early splenic regeneration. The quantity of CFU-C does not necessarily mirror the situation in the stem cell compartment. (author)

Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

1986-01-01

In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

Nuclear accidents and bone marrow graft

International Nuclear Information System (INIS)

Bernard, J.

1988-01-01

In case of serious contamination, the only efficacious treatment is the bone marrow grafts. The graft types and conditions have been explained. To restrict the nuclear accidents consequences, it is recommended to: - take osseous medulla of the personnel exposed to radiations and preserve it , that permits to carry out rapidly the auto-graft in case of accidents; - determine, beforehand, the HLA group of the personnel; - to register the voluntary donors names and addresses, and their HLA group, that permits to find easily a compatible donar in case of allo-graft. (author)

Impact of HLA diversity on donor selection in organ and stem cell transplantation.

Science.gov (United States)

Tiercy, Jean-Marie; Claas, Frans

2013-01-01

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

Directory of Open Access Journals (Sweden)

Rajkumar JS

2007-01-01

Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

Transplantation With Livers From Deceased Donors Older Than 75 Years

DEFF Research Database (Denmark)

Thorsen, Trygve; Aandahl, Einar Martin; Bennet, William

2015-01-01

BACKGROUND: The availability of donor organs limits the number of patients in need who are offered liver transplantation. Measures to expand the donor pool are crucial to prevent on-list mortality. The aim of this study was to evaluate the use of livers from deceased donors who were older than 75...... years. METHODS: Fifty-four patients who received a first liver transplant (D75 group) from 2001 to 2011 were included. Donor and recipient data were collected from the Nordic Liver Transplant Registry and medical records. The outcome was compared with a control group of 54 patients who received a liver...... graft from donors aged 20 to 49 years (D20-49 group). Median donor age was 77 years (range, 75-86 years) in the D75 group and 41 years (range, 20-49 years) in the D20-49 group. Median recipient age was 59 years (range, 31-73 years) in the D75 group and 58 years (range, 31-74 years) in the D20-49 group...

A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

2007-01-01

Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

Tetraspanin CD9 participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis.

Science.gov (United States)

Desterke, Christophe; Martinaud, Christophe; Guerton, Bernadette; Pieri, Lisa; Bogani, Costanza; Clay, Denis; Torossian, Frederic; Lataillade, Jean-Jacques; Hasselbach, Hans C; Gisslinger, Heinz; Demory, Jean-Loup; Dupriez, Brigitte; Boucheix, Claude; Rubinstein, Eric; Amsellem, Sophie; Vannucchi, Alessandro M; Le Bousse-Kerdilès, Marie-Caroline

2015-06-01

Primary myelofibrosis is characterized by clonal myeloproliferation, dysmegakaryopoiesis, extramedullary hematopoiesis associated with myelofibrosis and altered stroma in the bone marrow and spleen. The expression of CD9, a tetraspanin known to participate in megakaryopoiesis, platelet formation, cell migration and interaction with stroma, is deregulated in patients with primary myelofibrosis and is correlated with stage of myelofibrosis. We investigated whether CD9 participates in the dysmegakaryopoiesis observed in patients and whether it is involved in the altered interplay between megakaryocytes and stromal cells. We found that CD9 expression was modulated during megakaryocyte differentiation in primary myelofibrosis and that cell surface CD9 engagement by antibody ligation improved the dysmegakaryopoiesis by restoring the balance of MAPK and PI3K signaling. When co-cultured on bone marrow mesenchymal stromal cells from patients, megakaryocytes from patients with primary myelofibrosis displayed modified behaviors in terms of adhesion, cell survival and proliferation as compared to megakaryocytes from healthy donors. These modifications were reversed after antibody ligation of cell surface CD9, suggesting the participation of CD9 in the abnormal interplay between primary myelofibrosis megakaryocytes and stroma. Furthermore, silencing of CD9 reduced CXCL12 and CXCR4 expression in primary myelofibrosis megakaryocytes as well as their CXCL12-dependent migration. Collectively, our results indicate that CD9 plays a role in the dysmegakaryopoiesis that occurs in primary myelofibrosis and affects interactions between megakaryocytes and bone marrow stromal cells. These results strengthen the "bad seed in bad soil" hypothesis that we have previously proposed, in which alterations of reciprocal interactions between hematopoietic and stromal cells participate in the pathogenesis of primary myelofibrosis. Copyright© Ferrata Storti Foundation.

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

Directory of Open Access Journals (Sweden)

Bakonyi Neto Alexandre

2003-01-01

Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

OpenAIRE

Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

2014-01-01

Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of t...

Female-partnered and single women's contact motivations and experiences with donor-linked families.

Science.gov (United States)

Goldberg, A E; Scheib, J E

2015-06-01

-sharing were conducted with parents from one American donor insemination program. Findings are limited to individuals who were open enough to share their experiences and able to take the time to do so. As donor-linking services become established independently (e.g. donor insemination program registries) or by the government (e.g. Victoria, Australia's Voluntary Register), these findings provide evidence that linking services are valued by individuals affected by donor conception. Caution is warranted, however, in that some participants reported mismatched expectations, both across donor-linked families and within families (e.g. between partners), suggesting the need for information and guidance both during and after matching. Overall, the range and balance of reported positives and negatives indicate that donor-linking can provide individuals with support and donor origins information-which are particularly important when these are not available elsewhere. Clark University provided support. No competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

ISHKS joint registry: A preliminary report.

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Pachore, Jawahir A; Vaidya, Shrinand V; Thakkar, Chandrasekhar J; Bhalodia, Haresh Kumar P; Wakankar, Hemant M

2013-09-01

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are the most widely practiced surgical options for arthritis all over the world and its application is rising in India. Indian Society of Hip and Knee Surgeons (ISHKS) has established a joints registry and has been collecting data for last 6 years. All members of ISHKS are encouraged to actively participate in the registry. A simple two page knee and hip form can be downloaded from the website www.ishks.com. The information collected includes patient demographics, indication for surgery, implant details and in case of revision arthroplasty: the details of implants removed and the cause of failure of primary arthroplasty. These forms are mailed to the central registry office and the data is fed in computerized registry. Data collection started in October 2006. Joint registry is a very important initiative of ISHKS and till date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across India. Some important observations have emerged. Data of 34,478 TKAs was assessed: These included 8612 males (25%) and 25,866 females (75%). Average age was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range: 22 to 74 years). Average body mass index was 29.1 (Range: 18.1 to 42.9). The indication for TKA was osteoarthritis in 33,444 (97%) and rheumatoid arthritis in 759 (2.2%). Total of 3604 THA procedures were recorded. These included 2162 (60%) male patients and 1442 (40%) female patients. Average age was 52 years (Range 17 to 85 years) and average BMI was 25.8 (Range: 17.3 to 38.5). The indications for THA was AVN in 49%. The registry will become more meaningful in years to come. Active participation of all arthroplasty surgeons across India is vital for the success of the joints registry.

Inter- and Intrapersonal Barriers to Living Donor Kidney Transplant among Black Recipients and Donors.

Science.gov (United States)

Davis, LaShara A; Grogan, Tracy M; Cox, Joy; Weng, Francis L

2017-08-01

End-stage renal disease (ESRD) is more common among Blacks, but Blacks are less likely to receive a live donor kidney transplant (LDKT). The objective of this study is to identify barriers and coping mechanisms that Black LDKT recipients and donors experienced while receiving or donating a kidney. A qualitative study was conducted using structured interviews. Thematic analysis was used for data interpretation. All 20 participants identified as Black, with two participants identifying themselves as multiracial. The mean age for the 14 recipients was 60, and the average age for the 6 living donors was 47. Themes emerging from the data suggest both recipients and donors faced barriers in the LDKT experience. Recipients faced barriers associated with their denial and avoidance of the severity of their ESRD, their desire to maintain the privacy of their health status, and their refusal to approach potential donors. Donors encountered negative responses from others about the donors' desire to donate and the initial refusal of recipients to accept a LDKT offer. Recipients identified faith as a coping mechanism, while donors identified normalization of donation as their method of coping. Various types of social support helped donors and recipients navigate the transplant process. Black LDKT recipients and donors must overcome barriers prior to receiving or donating a kidney. Most of these barriers arise from communication and interactions with others that are either lacking or undesirable. Future interventions to promote LDKT among Blacks may benefit by specifically targeting these barriers.

Improving Organ Donor Registration Using Kiosks in Primary Care Clinics

Science.gov (United States)

Salim, Ali; Berry, Cherisse; Ley, Eric J.; Schulman, Danielle; Anderson, Jacqueline; Navarro, Sonia; Zheng, Ling; Chan, Linda S.

2015-01-01

Objective: In the USA, organ donor shortage is especially pronounced among minority ethnic populations such as Hispanics, who are 60% less likely to donate compared to non-Hispanic Whites. Recent evidence suggests that US Hispanics may consent to organ donation via a registry within a doctor's office. The objective of this study was to investigate…

Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus

International Nuclear Information System (INIS)

Kearns, M.; Lala, P.K.

1982-01-01

Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells

Common variables in European pancreatic cancer registries

DEFF Research Database (Denmark)

De Leede, E. M.; Sibinga Mulder, B. G.; Bastiaannet, E.

2016-01-01

Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer...... registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between...

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

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Samuel, G N; Kerridge, I H; Vowels, M; Trickett, A; Chapman, J; Dobbins, T

2007-10-01

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR). It also examines the ethnic diversity of those patients who, after requesting a haematopoietic stem cell transplantation in the 2-year period between 2003 and 2005, managed to find a suitably matched bone marrow or UCB donor. We show that the ethnic mix of donors to the SCBB has remained generally broad in source, is comparative to the Australian population, and is more diverse than the ABMDR. This, however, may still not be sufficient to substantially increase the likelihood of finding a donor for some ethnic minority groups.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

Science.gov (United States)

Martinez-Selles, Manuel; Almenar, Luis; Paniagua-Martin, Maria J; Segovia, Javier; Delgado, Juan F; Arizón, Jose M; Ayesta, Ana; Lage, Ernesto; Brossa, Vicens; Manito, Nicolás; Pérez-Villa, Félix; Diaz-Molina, Beatriz; Rábago, Gregorio; Blasco-Peiró, Teresa; De La Fuente Galán, Luis; Pascual-Figal, Domingo; Gonzalez-Vilchez, Francisco

2015-03-01

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women. © 2014 Steunstichting ESOT.

Allogeneic radiation chimeras respond to TNP-modified donor and host targets

International Nuclear Information System (INIS)

Lattime, E.C.; Gershon, H.E.; Stutman, O.

1980-01-01

Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 x DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 x CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells

CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus.

Science.gov (United States)

Mikulska, Małgorzata; Raiola, Anna Maria; Bruzzi, Paolo; Varaldo, Riccardo; Annunziata, Silvana; Lamparelli, Teresa; Frassoni, Francesco; Tedone, Elisabetta; Galano, Barbara; Bacigalupo, Andrea; Viscoli, Claudio

2012-01-01

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

International Nuclear Information System (INIS)

Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

1984-01-01

Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI

PROGRESS IN ORGAN DONATION AND TRANSPLANTATION IN RUSSIAN FEDERATION IN 2006–2010. 3RD REPORT OF NATIONAL REGISTRY

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S. V. Gautier

2011-01-01

Full Text Available The article presents the third report of the Registry of Russian transplant society, taking into account donor and transplant activity in the Russian Federation in 2006–2010. Data analysis proves clear positive trends during the last 5 years. The further progress is possible through the creation and modernization of regional donor infra- structures whose activities should be aimed at increasing of the number of donor hospitals and its rational use by expansion of brain death verification and performance of multiorgan procurement. 

Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry.

Science.gov (United States)

Fagioli, Franca; Quarello, Paola; Zecca, Marco; Lanino, Edoardo; Corti, Paola; Favre, Claudio; Ripaldi, Mimmo; Ramenghi, Ugo; Locatelli, Franco; Prete, Arcangelo

2014-06-01

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Diamond Blackfan anaemia (DBA). We report the transplantation outcome of 30 Italian DBA patients referred to the Italian Association of Paediatric Haematology and Oncology Registry between 1990 and 2012. This is one of the largest national registry cohorts of transplanted DBA patients. Most patients (83%) were allografted after 2000. A matched sibling donor was employed in 16 patients (53%), the remaining 14 patients (47%) were transplanted from matched unrelated donors. Twenty-eight of the 30 patients engrafted. One patient died at day +6 due to veno-occlusive disease without achieving neutrophil recovery and another patient remained transfusion-dependent despite the presence of a full donor chimerism. The 5-year overall survival and transplant-related mortality was 74·4% and 25·6%, respectively. Patients younger than 10 years as well as those transplanted after 2000 showed a significantly higher overall survival and a significantly lower risk of transplant-related mortality. No difference between donor type was observed. Our data suggest that allogeneic HSCT from a related or unrelated donor was a reasonable alternative to transfusion therapy in young and well chelated DBA patients. © 2014 John Wiley & Sons Ltd.

Expanding the donor pool: can the Spanish model work in the United States?

Science.gov (United States)

Chang, George J; Mahanty, Harish D; Ascher, Nancy L; Roberts, John P

2003-10-01

Since the creation of the Organizacion Nacional de Trasplantes (ONT) in 1989, the organ donation rate in Spain has doubled. Although often attributed to improved donor recruitment efforts, this increase may also represent higher utilization of marginal donors. Therefore, age-related donor recruitment in Spain and the US was evaluated. Data from the ONT, the US Scientific Registry of Transplant Recipients (SRTR), the US Census Bureau, and the Tempus databank of Spain's Instituto Nacional de Estadistica (INE) were analyzed. Between 1989 and 1999, the number of donors in Spain increased from 14.3 to 33.7 per million population (pmp; 136% increase) compared with an increase in the US from 16.2 to 21.5 donors pmp (33%). The largest difference between Spain and the US in the increased number of donors was in the 45-year-old group, representing 30.3% of donors in Spain in 1999 (44 donors pmp). If the US increased its older donor rates to match Spain's, an incremental 1235 donors per year would be realized. The high Spanish organ donation rates are largely attributable to increased use of older donors. Utilizing similar proportions of older donors in the US would increase the donor pool by almost 40%.

Bone Marrow Derivation of Interstitial Cells of Cajal in Small Intestine Following Intestinal Injury

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Dengqun Liu

2010-01-01

Full Text Available Interstitial cells of Cajal (ICCs in gastrointestinal tract are specialized cells serving as pacemaker cells. The origin of ICCs is currently not fully characterized. In this work, we aimed to study whether bone marrow-derived cells (BMDCs could contribute to the origin of ICCs in the muscular plexus of small intestine using GFP-C57BL/6 chimeric mice.Engraftment of BMDCs in the intestine was investigated for GFP expression. GFP positive bone marrow mononuclear cells reached a proportion of 95.65%±3.72% at different times in chimerism. Donor-derived cells distributed widely in all the layers of the gastrointestinal tract. There were GFP positive BMDCs in the myenteric plexus, which resembled characteristics of ICCs, including myenteric location, c-Kit positive staining, and ramified morphology. Donor-derived ICCs in the myenteric plexus contributed to a percentage ranging 9.25%±4.9% of all the ICCs in the myenteric plexus. In conclusion, here we described that donor-derived BMDCs might differentiate into gastrointestinal ICCs after radiation injury, which provided an alternative source for the origin of the ICCs in the muscular plexus of adult intestine. These results further identified the plasticity of BMDCs and indicated therapeutic implications of BMDCs for the gastrointestinal dysmotility caused by ICCs disorders.

Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

International Nuclear Information System (INIS)

Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

1982-01-01

Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed

Transfusão de plaquetas: do empirismo ao embasamento científico Platelet transfusion: from empiricism to scientific evidence

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Aline A. Ferreira

2010-01-01

Full Text Available Despite major advances in Brazilian blood transfusion therapy with a growing number of scientific publications, an increased number of repeat donors and a decline in serological ineligibility, a lack of conformity in the application of pre-transfusion tests that may compromise transfusion safety is still observed at transfusion agencies in the fringes of the blood transfusion therapy system. Additionally, although high rates of platelet transfusion refractoriness and significant rates of alloimmunization have been demonstrated in the international literature, few Brazilian centers have been concerned with the study of platelet alloimmunization and even fewer centers have evaluated the efficacy of platelet concentrate transfusion. As more than one million Brazilians, including many repeat blood donors, are listed in the National Bone Marrow Donor Registry (Redome, why not grant transfusion therapy services access to the HLA typing of these blood and marrow donors after obtaining their consent? And why not make use of the Redome data to evaluate the HLA compatibility of donors for alloimmunized patients who are candidates for bone marrow transfusion and who have already been typed? These measures, together with the identification of ABO and HPA antigens, will permit a complete assessment of platelet immunology, will guarantee the transfusion safety of this blood component, and will put Brazil at the same level as the so-called developed countries in terms of transfusion medicine.

Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

Science.gov (United States)

Benito, Juliana; Ramirez, Marc S; Millward, Niki Zacharias; Velez, Juliana; Harutyunyan, Karine G; Lu, Hongbo; Shi, Yue-Xi; Matre, Polina; Jacamo, Rodrigo; Ma, Helen; Konoplev, Sergej; McQueen, Teresa; Volgin, Andrei; Protopopova, Marina; Mu, Hong; Lee, Jaehyuk; Bhattacharya, Pratip K; Marszalek, Joseph R; Davis, R Eric; Bankson, James A; Cortes, Jorge E; Hart, Charles P; Andreeff, Michael; Konopleva, Marina

2016-04-01

To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models. Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models. Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells. These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins. ©2015 American Association for Cancer Research.

Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

Science.gov (United States)

Chang, Ying-Jun; Huang, Xiao-Jun

2011-01-01

In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G-CSF-stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation. © 2010 John Wiley & Sons A/S.

Bone marrow transplantation (1958-1978): conditioning and graft-versus-host disease, indications in aplasias and leukemias

International Nuclear Information System (INIS)

Mathe, G.; Schwarzenberg, L.

1979-01-01

Bone marrow transplantation (BMT), which stimulated great hope for treatment of aplasias and leukemias in 1958 following our first success in grafting this tissue, is, after a long period of study and development, experiencing renewed interest since it is now possible to obtain, in case of transplantation with genotypically matched sibling donors, 70% long survival (cures) in aplasia (under the condition that the recipient is not sensitized by previous transfusions) and in leukemia (under the condition that the recipient is transplanted in a period of remission and is not sensitized by transfusions). When the patient does not possess any genotypically matched donor, a trial of incompatible bone marrow transplantation after conditioning with antilymphocyte serum is reasonable, since we have obtained good, although unexplained, results with this method, which should be pursued. In any case, these transplants must be done in intensive care units in hemato-oncology departments

Bone marrow transplantation (1958-1978): conditioning and graft-versus-host disease, indications in aplasias and leukemias

Energy Technology Data Exchange (ETDEWEB)

Mathe, G; Schwarzenberg, L [Hopital Paul Brousse, 94 - Villejuif (France)

1979-06-01

Bone marrow transplantation (BMT), which stimulated great hope for treatment of aplasias and leukemias in 1958 following our first success in grafting this tissue, is, after a long period of study and development, experiencing renewed interest since it is now possible to obtain, in case of transplantation with genotypically matched sibling donors, 70% long survival (cures) in aplasia (under the condition that the recipient is not sensitized by previous transfusions) and in leukemia (under the condition that the recipient is transplanted in a period of remission and is not sensitized by transfusions). When the patient does not possess any genotypically matched donor, a trial of incompatible bone marrow transplantation after conditioning with antilymphocyte serum is reasonable, since we have obtained good, although unexplained, results with this method, which should be pursued. In any case, these transplants must be done in intensive care units in hemato-oncology departments.

Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

Science.gov (United States)

Yin, Yuxin; Lan, James H; Nguyen, David; Valenzuela, Nicole; Takemura, Ping; Bolon, Yung-Tsi; Springer, Brianna; Saito, Katsuyuki; Zheng, Ying; Hague, Tim; Pasztor, Agnes; Horvath, Gyorgy; Rigo, Krisztina; Reed, Elaine F; Zhang, Qiuheng

2016-01-01

Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA. Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C) from promotor to 3' UTR. Class II genes (DRB1, DQB1) were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML) format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing. Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%), 92 rare alleles (0.091%) and 42 exon novelties (0.042%). Long

Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

Directory of Open Access Journals (Sweden)

Yuxin Yin

Full Text Available Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT, HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP registry donors using long-range PCR by next generation sequencing (NGS approach on buccal swab DNA.Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C from promotor to 3' UTR. Class II genes (DRB1, DQB1 were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing.Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%, 92 rare alleles (0.091% and 42 exon novelties (0.042%.Long

Clinical presentations of 23 half-siblings from a mosaic neurofibromatosis type 1 sperm donor.

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Ejerskov, C; Farholt, S; Skovby, F; Vestergaard, E M; Haagerup, A

2016-03-01

The Danish sperm donor number 7042 has fathered several offspring with neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss-of-function mutations in the NF1 gene and more than 1000 NF1 mutations are identified. Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic deletion involving exons 15-29 in the NF1 gene. At the two Danish reference centres for NF1 patients, we evaluated 23 half-siblings from the donor. Nine were diagnosed with NF1. The severity grade of NF1 progressed from minimal to mild/moderate within 3 years of follow-up. The NF1 phenotype shows great variability in intra- and inter-family expressivity and to date only two NF1 genotype-phenotype correlations have been established. This rare possibility of a long-term follow-up of a cohort of half-siblings with NF1 makes further studies including phenotypic variability and search for modifier genes possible. To achieve this goal, we have initiated The International Donor 7042 NF1 Offspring Registry. Research facilitated via this registry may reveal important new knowledge of clinical characteristics and prognostics for the specific NF1 genotype and thereby contribute to future individualised targeted clinical follow-up and treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS)--registry Swabia.

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Nagel, Gabriele; Unal, Hatice; Rosenbohm, Angela; Ludolph, Albert C; Rothenbacher, Dietrich

2013-02-17

The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2-5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case-control study was implemented based on the registry that also included the collection of various biological materials.Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case-control study. All participants in the case-control study provided also a blood sample. The prospective part of the study is ongoing. The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms.

Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

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Domaratskaya, E.; Starostin, V.

The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations

Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element

International Nuclear Information System (INIS)

Hinrichs, D.J.; Wegmann, K.W.; Dietsch, G.N.

1987-01-01

The adoptive transfer of clinical and histopathologic signs of experimental allergic encephalomyelitis (EAE) requires MHC compatibility between cell donor and cell recipient. The results of adoptive transfer studies using F1 to parent bone marrow chimeras as recipients of parental-derived BP-sensitive spleen cells indicate that this restriction is not expressed at the level of the endothelial cell but is confined to the cells of bone marrow derivation. Furthermore, these results indicate that the development of EAE is not dependent on the activity of MHC-restricted cytotoxic cells

Discovery of the rare HLA-B*39:77 allele in an unrelated Taiwanese bone marrow stem cell donor using the sequence-based typing method.

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Yang, K L; Lee, S K; Lin, P Y

2013-08-01

We detected a rare HLA-B locus allele, B*39:77, in a Taiwanese unrelated marrow stem cell donor in our routine HLA sequence-based typing (SBT) exercise for a possible haematopoietic stem cell donation. In exons 2, 3 and 4, the DNA sequence of B*39:77 is identical to the sequence of B*39:01:01:01 except one nucleotide at nucleotide position 733 (G->A) in exon 4. The nucleotide variation caused one amino acid alteration at residue 221 (Gly->Ser). B*39:77 was probably derived from a nucleotide substitution event involving B*39:01:01:01. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with B*39:77 may be deduced as A*02:01-B*39:77-C*07:02-DRB1*08:03-DQB1*06:01. Our discovery of B*39:77 in Taiwanese adds further polymorphism of B*39 variants in Taiwanese population. © 2013 John Wiley & Sons Ltd.

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

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Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

2014-01-01

Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection

DEFF Research Database (Denmark)

Hokland, M; Jacobsen, N; Ellegaard, J

1988-01-01

Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes......) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90...

Treated of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue

International Nuclear Information System (INIS)

Yasumizu, R.; Sugiura, K.; Iwai, H.

1987-01-01

Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans

In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

International Nuclear Information System (INIS)

Lum, L.G.; Seigneuret, M.C.; Storb, R.F.; Witherspoon, R.P.; Thomas, E.D.

1981-01-01

Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation

Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

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Doney, K; Buckner, C D; Sale, G E; Ramberg, R; Boyd, C; Thomas, E D [Fred Hutchinson Cancer Research Institute; Washington Univ., Seattle (USA). School of Medicine)

1978-01-01

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.

Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Doney, K.; Buckner, C.D.; Sale, G.E.; Ramberg, R.; Boyd, C.; Thomas, E.D.; Washington Univ., Seattle

1978-01-01

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration. (Author)

Cohort profile: the TrueNTH Global Registry - an international registry to monitor and improve localised prostate cancer health outcomes.

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Evans, Sue M; Millar, Jeremy L; Moore, Caroline M; Lewis, John D; Huland, Hartwig; Sampurno, Fanny; Connor, Sarah E; Villanti, Paul; Litwin, Mark S

2017-11-28

Globally, prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry project was established as an international registry monitoring care provided to men with localised prostate cancer (CaP). Sites with existing CaP databases in Movember fundraising countries were invited to participate in the international registry. In total, 25 Local Data Centres (LDCs) representing 113 participating sites across 13 countries have nominated to contribute to the project. It will collect a dataset based on the International Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised CaP. A governance strategy has been developed to oversee registry operation, including transmission of reversibly anonymised data. LDCs are represented on the Project Steering Committee, reporting to an Executive Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have been established. A project was undertaken to compare existing datasets, understand capacity at project commencement (baseline) to collect the ICHOM dataset and assist in determining the final data dictionary. 21/25 LDCs provided data dictionaries for review. Some ICHOM data fields were well collected (diagnosis, treatment start dates) and others poorly collected (complications, comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory fields due to poor capture by most existing registries. Participating sites will transmit data through a web interface biannually to the DCC. Recruitment to the TrueNTH Global Registry-PCOR project will commence in late 2017 with sites progressively contributing reversibly anonymised data following ethical review in local regions. Researchers will have capacity to source deidentified data after the establishment phase. Quality indicators are to be established through a modified Delphi approach in later 2017, and it is anticipated that reports on

Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

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Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

2017-07-01

The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

Rapid and automated processing of bone marrow grafts without Ficoll density gradient for transplantation of cryopreserved autologous or ABO-incompatible allogeneic bone marrow.

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Schanz, U; Gmür, J

1992-12-01

The growing number of BMTs has increased interest in safe and standardized in vitro bone marrow processing techniques. We describe our experience with a rapid automated method for the isolation of mononuclear cells (MNC) from large volumes of bone marrow using a Fenwal CS-3000 cell separator without employing density gradient materials. Forty bone marrow harvests with a mean volume of 1650 +/- 307 ml were processed. A mean of 75 +/- 34% (50 percentile range 54-94%) of the original MNCs were recovered in a volume of 200 ml with only 4 +/- 2% of the starting red blood cells (RBC). Removal of granulocytes, immature myeloid precursors and platelets proved to be sufficient to permit safe cryopreservation and successful autologous BMT (n = 25). Allogeneic BMT (n = 14, including three major ABO-incompatible) could be performed without additional manipulation. In both groups of patients timely and stable engraftment comparable to historical controls receiving Ficoll gradient processed autologous (n = 17) or unprocessed allogeneic BMT (n = 54) was observed. Moreover, 70 +/- 14% of the RBC could be recovered from the grafts. They were used for autologous RBC support of donors, rendering unnecessary autologous blood pre-donations.

Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

International Nuclear Information System (INIS)

Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

1985-01-01

Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and 14 C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of 14 C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose

Describing the first 2000 registrations to the Research Registry®: A study protocol

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Alexander J. Fowler

Full Text Available Background: In 2013, the Declaration of Helsinki was updated and required the registration of all research studies involving human participants. Prior registries focussed on the registration of clinical trials and systematic reviews, and we estimate that only 10% of observational research is registered in a publically accessible registry. The Research Registry® was established to provide a venue of registration for any study, prospectively or retrospectively, involving human participants. This protocol describes the analysis for the first 2000 registrations received to the Research Registry®. Methods and analysis: Data for each registration to the Research Registry® (www.researchregistry.com, adapted from the World Health Organisation minimum data set, has been collected since the launch of the registry in 2015. A weekly curation process ensures that inappropriate registrations, such as duplicate studies or those not involving human participants, are removed from the registry. We will present the characteristics of the first 2000 registrations and how they have changed overtime. A quality score will be calculated for each registration by two independent teams, and inter-rater reliability will be calculated. Funding sources of work registered will also be presented. This process will also be performed for the systematic review portion of the registry (‘The Review Registry’, which will be considered separately. Ethics and dissemination: Ethical approval is not required for this study as it involves no human participants. The findings will be presented at international conferences and published in a peer reviewed journal.

Graft-versus-leukemia, donor selection for adoptive immunotherapy in mice

International Nuclear Information System (INIS)

LeFeber, W.P.; Truitt, R.L.; Rose, W.C.; Bortin, M.M.

1977-01-01

The optimal donor for adoptive immunotherapy would exhibit great antitumor reactivity and no antihost reactivity. Immunocompetent cells from 11 strains of mice were tested in vivo for their reactivity against a long-passage AKR acute lymphoblastic leukemia and against immunosuppressed nonleukemic AKR mice. Donor mice were syngeneic, unprimed H-2 compatible, primed H-2 compatible, congenic, or H-2 incompatible with AKR. Bioassays were used to evaluate the relative graft-vs.-leukemia (GvL) reactivity and the relative graft-vs.-host (GvH) reactivity of transplanted bone marrow and lymph-node cells from the panel of donors. No significant GvL reactivity was found when cells from syngeneic, unprimed H-2 compatible, or congenic donors were tested. H-2 compatible donors that were immunized with γ-irradiated AKR leukemic spleen cells showed modest GvL reactivity, but associated with the immunization was a disproportionate increase in acute and delayed GvH mortality. Among the H-2 mismatched donors, mice of the SJL strain appeared to most closely approach the ideal because of least intense GvH reactivity and maximal GvL reactivity. As measured in these experiments there was no correlation between the severity of GvH disease and the efficacy of the GvL reaction; GvL reactivity in unprimed donors was always associated with H-2 incompatibility; disparity between donor and recipient at H-2 did not guarantee an effective GvL reaction; and the increase in GvL reactivity obtained by immunizing H-2 compatible donors was overshadowed by the increase in GvH disease

US Transuranium Registry report on the 241Am content of a whole body. Part I: Introduction and history of the case

International Nuclear Information System (INIS)

Breitenstein, B.D.; Newton, C.E.; Norris, H.T.

1985-01-01

The first whole-body analysis of the U.S. Transuranium Registry was initiated in 1979. The donor was a 49-yr-old male Caucasian radiochemist who died of metastatic malignant melanoma. The donor had a recognized, longstanding 241 Am internal deposition first identified in a routine urine sample in 1958. A summary of the clinical and postmortem findings is presented with the chronologic sequence of the procedures

Role of donor lymphoid cells in the transfer of allograft tolerance

International Nuclear Information System (INIS)

Pierce, G.E.; Watts, L.M.

1985-01-01

Tolerance to murine skin allografts across a MHC disparity was induced by conditioning primary hosts with sublethal fractionated total-body irradiation (FTBI) and transfusion of allogeneic bone marrow (BM). Tolerance could be adoptively transferred to secondary hosts conditioned by FTBI with infusion of spleen cells from hosts bearing intact skin allografts greater than 60 days. Tolerance could not be transferred by tolerant host spleen (THS) preparations from which cells of the donor genotype had been deleted by cytotoxic alloantisera. Deletion of host genotype cells, however, did not diminish the capability of THS to transfer tolerance. All of the tolerizing activity of THS appeared to reside within cells of the donor genotype. Small numbers of normal donor spleen cells could induce tolerance in FTBI hosts but only at the expense of very high mortality, in contrast to the low mortality observed with tolerizing injections of allogeneic donor cells from THS or injections of normal semiallogeneic F1 hybrid spleen cells. If an active immune response is responsible for tolerance induction/transfer in this model, allogeneic donor lymphoid cells derived from BM, in contrast to donor spleen cells, must be capable of mounting this response without concomitant severe GVHD. In future experiments, cells of donor genotype can be isolated from THS and purified in sufficient numbers to compare their tolerizing efficiency vs. that of normal donor cells, detect possible suppression of normal host cell alloreactivity in vitro and identify the donor cell phenotypes involved

Analysis of the motivation for hematopoietic stem cell donation.

Science.gov (United States)

Aurelio, M T; Aniasi, A; Haworth, S E; Colombo, M B; Dimonopoli, T; Mocellin, M C; Poli, F; Torelli, R; Crespiatico, L; Serafini, M; Scalamogna, M

2011-05-01

The Italian Bone Marrow Donor Register is the institutional organization for management of unrelated hematopoietic stem cell donors. The law requires only a donor's clinical history, but not a psychosocial profile for registration. We have studied the donor's motivation for enlistment on the donor registry and the medical staff's need for this information to interact correctly with the donor. For this purpose we distributed a questionnaire to new donors at the 20 centers in the Lombardy Region over a period of 1 year. The analysis of the responses revealed a prevalence of extrinsic motivations that would not ensure continued registration for donation. Therefore, it is necessary that the donor be well informed and better educated about all aspects of donation, in order to produce a shift to an intrinsic motivation. This objective can be facilitated via professional training of health workers in communication. Copyright © 2011 Elsevier Inc. All rights reserved.

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

Science.gov (United States)

Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

2015-11-01

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. 2

International Nuclear Information System (INIS)

Mulder, A.H.; Visser, J.W.M.; Zoetelief, J.; Bekkum, D.W. van

1988-01-01

The time of entry of prothymocytes into the thymus after lethal irradiation and bone marrow transplantation (BMT) was determined by exposing the thymus only or the whole body with the thymus shielded to a second irradiation after different intervals. The repopulation of the thymus by donor type cells was determined by a thymus repopulation assay using donor specific markers. Reirradiation of the thymus kills the prothymocytes that have entered the thymus during the interval. It was found that reirradiation of the thymus from 48 hours after BMT onwards increasingly delayed thymus regeneration. This shows that donor prothymocytes do not enter the thymus until about 2 days after BMT and that they continue to do so during at least 3 subsequent days. In the second reirradiation protocol thymus regeneration occurred earlier in the shielded thymus than in thymuses of whole body irradiated mice. Earlier thymus regeneration was not seen in mice that were reirradiated at 24 hours after BMT, but occurred only when irradiation took place at 48 hours and later. These data are consistent with those obtained in the first protocol. The results are in contradiction with results of direct homing experiments, which showed entrance of donor cells within 3 hours after BMT. A functional assay demonstrated that the early appearing cells cannot be prothymocytes. In retransplantation experiments it was shown that the bone marrow may indeed be the initial homing site of prothymocytes. 14 refs.; 5 figs.; 1 table

Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS - registry Swabia

Directory of Open Access Journals (Sweden)

Nagel Gabriele

2013-02-01

Full Text Available Abstract Background The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS registry Swabia, located in the South of Germany. Methods/Design The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010 and prospective (from 01.10.2010 collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case–control study was implemented based on the registry that also included the collection of various biological materials. Retrospectively, 420 patients (222 men and 198 women were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case–control study. All participants in the case–control study provided also a blood sample. The prospective part of the study is ongoing. Discussion The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms.

Subtotal body irradiation with linear accelerator as preparation for marrow engraftment in aplastic anemia

International Nuclear Information System (INIS)

Walbom-Joergensen, S.; Ernst, P.

1979-01-01

Two cases of multitransfused severe aplastic anemia were retransplanted with bone marrow from the same HLA compatible sibling donors after subtotal body irradiation (800 r). Only minor non hematologic toxicity was observed. No permanent take was seen in relation to this procedure. During the survival time of the patients (78-120 days) no signs of interstitial pneumonia were observed

HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease

DEFF Research Database (Denmark)

Ødum, Niels; Platz, P; Jakobsen, B K

1987-01-01

Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP...... a role as transplantation antigens....

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

Science.gov (United States)

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-06-01

The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

Experiences and Motives of Australian Single Mothers by Choice who make Early Contact with their Child’s Donor Relatives

Science.gov (United States)

Dempsey, Deborah J

2016-01-01

Abstract An increasing number of Australian parents of donor-conceived children are making contact with their child’s donor relatives prior to their child reaching the age of majority. This process, often referred to as ‘donor linking’, can be achieved in Australia through either formal or informal mechanisms. Formal mechanisms exist in three states, each of which has legislation enabling donor linking in certain circumstances. Donor linking may also be achieved through informal mechanisms, such as online donor registries, social media searches, direct-to-consumer genetic testing, and fertility clinics which act as intermediaries between donors and recipients. Drawing on qualitative interview data, this article explores the donor linking practices of twenty-five single women who conceived using donated gametes. The findings suggest that early contact with donors is extremely popular among single women and that, even when formal legislative mechanisms are available, informal linking remains common. PMID:28137771

Clinical studies on bone marrow transplantation of acute leukemia and aplastic anemia

International Nuclear Information System (INIS)

Morishima, Yasuo

1979-01-01

Since 1974, we have done bone marrow transplantation (BMT) in six patients of acute leukemia and two of aplastic anemia. Leukemia patients were premedicated by CY+TBI method; cyclophosphamide (CY) 60 mg/kg/day was administered for two successive days and two days later, total body irradiation (TBI) was done in a dose of 800 - 1000 rad at a rate of 20-28 rad/min by linear accerelator. Patients with aplastic anemia were premedicated by CY method; CY 50 mg/kg/day for four successive days. Bone marrow graft was obtained from donor under general anesthesia. The nucleated bone marrow cells, ranged from 0.7 x 10 10 to 1.4 x 10 10 were transfused into the patient intravenously. Any lethal side effects did not develop in all patient during these procedures. Two died on day 10 and 12 with septicemia. The other 6 patients showed engraftment of bone marrow indicated by rising blood counts, return of marrow cellularity and in one case by blood cytogenetic markers. Relapse of leukemia did not occur in five patients treated with CY + TBI method. Three patients with allogeneic BMT developed moderately severe to severe Graft versus Host Disease. Survival time after BMT were 12, 35, 63, 68, 98, 125 days. 15 months in leukemia, and 10 days, 12 + months in aplastic anemia. (author)

Section 4. Further expanding the criteria for HCC in living donor liver transplantation: the Tokyo University experience.

Science.gov (United States)

Tamura, Sumihito; Sugawara, Yasuhiko; Kokudo, Norihiro

2014-04-27

In Asia, evidence-based guidelines for the management of hepatocellular carcinoma (HCC) have evolved, including the option of liver transplantation. Because of the continuing serious organ shortage, however, living donor liver transplantation (LDLT) remains the mainstream in Japan. Unlike deceased donor transplantation, living donor transplantation is not always limited by the restrictions imposed by the nationwide organ allocation system. The decision for transplantation may depend on institutional or case-by-case considerations, balancing the will of the donor, the operative risk, and the overall survival benefit. Cumulative data from the Japanese national multicenter registry analysis as well as individual center experiences suggest further expanding the criteria for LDLT for HCC from the Milan criteria is feasible with acceptable outcomes.

Experiences and Motives of Australian Single Mothers by Choice Who Make Early Contact with their Child's Donor Relatives.

Science.gov (United States)

Kelly, Fiona J; Dempsey, Deborah J

2017-01-30

An increasing number of Australian parents of donor-conceived children are making contact with their child's donor relatives prior to their child reaching the age of majority. This process, often referred to as 'donor linking', can be achieved in Australia through either formal or informal mechanisms. Formal mechanisms exist in three states, each of which has legislation enabling donor linking in certain circumstances. Donor linking may also be achieved through informal mechanisms, such as online donor registries, social media searches, direct-to-consumer genetic testing, and fertility clinics which act as intermediaries between donors and recipients. Drawing on qualitative interview data, this article explores the donor linking practices of twenty-five single women who conceived using donated gametes. The findings suggest that early contact with donors is extremely popular among single women and that, even when formal legislative mechanisms are available, informal linking remains common. © The Author 2017. Published by Oxford University Press.

Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

DEFF Research Database (Denmark)

Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian

2003-01-01

Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maxi...

Full likelihood analysis of genetic risk with variable age at onset disease--combining population-based registry data and demographic information.

Directory of Open Access Journals (Sweden)

Janne Pitkäniemi

Full Text Available BACKGROUND: In genetic studies of rare complex diseases it is common to ascertain familial data from population based registries through all incident cases diagnosed during a pre-defined enrollment period. Such an ascertainment procedure is typically taken into account in the statistical analysis of the familial data by constructing either a retrospective or prospective likelihood expression, which conditions on the ascertainment event. Both of these approaches lead to a substantial loss of valuable data. METHODOLOGY AND FINDINGS: Here we consider instead the possibilities provided by a Bayesian approach to risk analysis, which also incorporates the ascertainment procedure and reference information concerning the genetic composition of the target population to the considered statistical model. Furthermore, the proposed Bayesian hierarchical survival model does not require the considered genotype or haplotype effects be expressed as functions of corresponding allelic effects. Our modeling strategy is illustrated by a risk analysis of type 1 diabetes mellitus (T1D in the Finnish population-based on the HLA-A, HLA-B and DRB1 human leucocyte antigen (HLA information available for both ascertained sibships and a large number of unrelated individuals from the Finnish bone marrow donor registry. The heterozygous genotype DR3/DR4 at the DRB1 locus was associated with the lowest predictive probability of T1D free survival to the age of 15, the estimate being 0.936 (0.926; 0.945 95% credible interval compared to the average population T1D free survival probability of 0.995. SIGNIFICANCE: The proposed statistical method can be modified to other population-based family data ascertained from a disease registry provided that the ascertainment process is well documented, and that external information concerning the sizes of birth cohorts and a suitable reference sample are available. We confirm the earlier findings from the same data concerning the HLA-DR3

Bone marrow aspiration

Science.gov (United States)

Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

United States Transuranium Registry. Annual report, October 1, 1983-September 30, 1984

International Nuclear Information System (INIS)

Swint, M.J.; Kathren, R.L.

1985-04-01

This report provides an overview of the objectives, program, facilities and FY-84 accomplishments of the United States Transuranium Registry. Specific activities summarized include postmortem radiochemical analysis of two whole bodies, one with a significant deposition of 241 Am and the other with a deposition of 239 Pu. Results of a followup of early Manhattan District workers as potential registrants, a possible relationship between actinide concentration in bone and ash content, and interlaboratory cooperative activities are briefly discussed along with the initiation of studies of actinides in bone marrow and hair

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

Science.gov (United States)

Kurekci, Emin; Küpesiz, Alphan; Anak, Sema; Öztürk, Gülyüz; Gürsel, Orhan; Aksoylar, Serap; Ileri, Talia; Kuşkonmaz, Barış; Eker, İbrahim; Cetin, Mualla; Tezcan Karasu, Gülsün; Kaya, Zühre; Fışgın, Tunç; Ertem, Mehmet; Kansoy, Savaş; Yeşilipek, Mehmet Akif

2017-05-01

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 10 6 CD 34 + cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Statewide Quality Improvement Initiative to Reduce Early Elective Deliveries and Improve Birth Registry Accuracy.

Science.gov (United States)

Kaplan, Heather C; King, Eileen; White, Beth E; Ford, Susan E; Fuller, Sandra; Krew, Michael A; Marcotte, Michael P; Iams, Jay D; Bailit, Jennifer L; Bouchard, Jo M; Friar, Kelly; Lannon, Carole M

2018-04-01

To evaluate the success of a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data accuracy rapidly and at scale in Ohio. Between February 2013 and March 2014, participating hospitals were involved in a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data. This initiative was designed as a learning collaborative model (group webinars and a single face-to-face meeting) and included individual quality improvement coaching. It was implemented using a stepped wedge design with hospitals divided into three balanced groups (waves) participating in the initiative sequentially. Birth registry data were used to assess hospital rates of nonmedically indicated inductions at less than 39 weeks of gestation. Comparisons were made between groups participating and those not participating in the initiative at two time points. To measure birth registry accuracy, hospitals conducted monthly audits comparing birth registry data with the medical record. Associations were assessed using generalized linear repeated measures models accounting for time effects. Seventy of 72 (97%) eligible hospitals participated. Based on birth registry data, nonmedically indicated inductions at less than 39 weeks of gestation declined in all groups with implementation (wave 1: 6.2-3.2%, Pinitiative, they saw significant decreases in rates of early elective deliveries as compared with wave 3 (control; P=.018). All waves had significant improvement in birth registry accuracy (wave 1: 80-90%, P=.017; wave 2: 80-100%, P=.002; wave 3: 75-100%, Pinitiative enabled statewide spread of change strategies to decrease early elective deliveries and improve birth registry accuracy over 14 months and could be used for rapid dissemination of other evidence-based obstetric care practices across states or hospital systems.

It 'did what it said on the tin' - participant's views of the content and process of donor conception parenthood preparation workshops.

Science.gov (United States)

Crawshaw, Marilyn; Montuschi, Olivia

2014-03-01

Using donor conception treatment for family building brings challenges as well as rewards. As social model approaches to managing genetic difference within families gradually replace earlier medical models, parents are encouraged to be open with their children about their origins amidst greater social acceptance. Little is known about effective interventions to help prospective parents prepare for such family life. A survey was sent to participants in 16 Preparation for Parenthood workshops run in England by Donor Conception Network, a peer support organisation, between 2008 and 2010. The 79 respondents (32.4% response) included heterosexual couples, lesbian couples and single women considering sperm, egg or double donation. In 86% couples, both partners responded. The use of a range of techniques, a family lifespan approach, facilitators with personal as well as professional experience, medical and psychosocial specialists, and access to peer support were well received. Results suggest the value of attending cognitive and affective processes, acknowledging the impact of stigma and discussing how the donor's biography/presence can be conjoined with that of the new family. Findings suggest workshop approaches to donor conception parenthood preparation can be useful for prospective lesbian/single women/heterosexual-headed families considering donor conception. Such interventions have not previously been reported.

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

Science.gov (United States)

Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

Relative frequencies of DRB1*11 alleles and their DRB3 associations in five major population groups in a United States bone marrow registry.

Science.gov (United States)

Tang, T F; Huang, A Y; Pappas, A; Slack, R; Ng, J; Hartzman, R J; Hurley, C K

2000-08-01

One hundred sixty-one individuals from each of five US population groups, Caucasians (CAU), African Americans (AFA), Asians/Pacific Islanders (API), Hispanics (HIS), and Native Americans (NAT), were randomly selected from a volunteer bone marrow registry database consisting of 14,452 HLA-DRB1*11 positive individuals. This sampling provided at least an 80% probability of detecting a rare allele that occurred at 1% in the DRB1*11 positive population. Samples were typed for DRB1*11 alleles by polymerase chain reaction-sequence specific oligonucleotide probe typing (PCR-SSOP). A total of 10 DRB1*11 alleles out of 27 possible alleles were detected. The distribution and diversity of DRB1*11 alleles varied among populations although DRB1*1101 was the predominant DRB1*11 allele in all populations. Caucasians were the least diversified; only four common alleles (DRB1*1101-*1104) were observed. As well as the four common alleles, other groups also carried one or two other less frequent alleles including DRB1*1105 (API), *1106 (API), *1110 (AFA), *1114 (HIS), *1115 (NAT), and *1117 (AFA). A subset (418) of these individuals were also typed for DRB3 alleles. Most (97.6%) showed a strong association of DRB1*11 with DRB3*0202.

Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

International Nuclear Information System (INIS)

Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

1988-01-01

From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) [or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)], 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group

HLA-B8 association with late-stage melanoma – an immunological lesson?

Directory of Open Access Journals (Sweden)

Andersen Mads

2006-03-01

Full Text Available Abstract Background Differences in HLA allele frequencies between the diseased and healthy populations may signify efficient immune responses, a notion that has been successfully tested for infectious diseases or for association with genetic elements involved in a distinct type of immunity. This retrospective study is intended to detect differences in MHC class I carrier frequencies of advanced melanoma patients compared to healthy bone marrow donors. Methods The HLA-A and -B carrier frequencies of 748 stage IV melanoma patients retrieved from serotyping at 6 different centers in Germany were compared using a chi-square test to 13,386 fully HLA typed bone marrow donors registered in the German national bone marrow donor registry. Results The comparison of HLA carrier frequencies in advanced cancer patients with healthy bone marrow donors revealed a significant decrease in HLA-B8 carrier frequencies, which was also apparent in patients with advanced disease compared to patients with loco-regional disease. Conclusion The data suggest that protective immune responses restricted to distinct MHC class I molecules may be operational in a subset of melanoma patients, which is the prerequisite for a large scale screen for the corresponding epitopes. Alternatively, the known association of the ancestral haplotype HLA-A1, -B8 and -DR3 with genetic elements such as distinct TNF-α alleles might have a protective effect on disease progression. In any case, identification of the cause of protection within this patient subset might lead to a significant improvement in the efficacy of current immunotherapeutic approaches.

Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

Science.gov (United States)

Pan, L; Bressler, S; Cooke, K R; Krenger, W; Karandikar, M; Ferrara, J L

1996-10-01

Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

Correction of lysosomal enzyme deficiency in various organs of beta-glucuronidase-deficient mice by allogeneic bone marrow transplantation

NARCIS (Netherlands)

Hoogerbrugge, P. M.; Poorthuis, B. J.; Mulder, A. H.; Wagemaker, G.; Dooren, L. J.; Vossen, J. M.; van Bekkum, D. W.

1987-01-01

The correction of lysosomal enzyme deficiency was investigated for various organs of beta-glucuronidase-deficient C3H/Rij mice after allogeneic bone marrow transplantation from an enzymatically normal donor strain (C57BL/Rij). In the hemopoietic organs, the enzyme level increased to levels found in

Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission

DEFF Research Database (Denmark)

Nagler, Arnon; Labopin, Myriam; Shimoni, Avichai

2012-01-01

Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data...... to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from...

Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

Science.gov (United States)

Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N

2017-01-01

With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

Directory of Open Access Journals (Sweden)

Itır Sirinoglu Demiriz

2012-01-01

Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

Donor body mass index is an important factor that affects peripheral blood progenitor cell yield in healthy donors after mobilization with granulocyte-colony-stimulating factor.

Science.gov (United States)

Chen, Jian; Burns, Kevin M; Babic, Aleksandar; Carrum, George; Kennedy, Martha; Segura, Francisco J; Garcia, Salvador; Potts, Sandra; Leveque, Christopher

2014-01-01

The use of hematopoietic progenitor cell (HPC) transplantation has rapidly expanded in recent years. Currently, several sources of HPCs are available for transplantation including peripheral blood HPCs (PBPCs), cord blood cells, and marrow cells. Of these, PBPC collection has become the major source of HPCs. An important variable in PBPC collection is the response to PBPC mobilization, which varies significantly and sometime causes mobilization failure. A retrospective study of 69 healthy donors who underwent PBPC donation by leukapheresis was performed. All of these donors received 10 μg/kg/day or more granulocyte-colony-stimulating factor (G-CSF) for 5 days before PBPC harvest. Donor factors were evaluated and correlated with mobilization responses, as indicated by the precollection CD34 count (pre-CD34). Donors with a pre-CD34 of more than 100 × 10(6) /L had higher body mass index (BMI) compared with donors whose pre-CD34 was 38 × 10(6) to 99 × 10(6) /L or less than 38 × 10(6) /L (32.0 ± 1.04 kg/m(2) vs. 28.7 ± 0.93 kg/m(2) vs. 25.9 ± 1.27 kg/m(2) , respectively; p donors with high BMIs had higher pre-CD34 on a per-kilogram-of-body-weight basis compared with donors with low BMIs. BMI is an important factor that affects donor's response to mobilization and consequently the HPC yield. This effect may be due to a relatively high dose of G-CSF administered to donors with higher BMI or due to the presence of unknown intrinsic factors affecting mobilization that correlate with the amount of adipose tissue in each donor. © 2013 American Association of Blood Banks.

Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

International Nuclear Information System (INIS)

Onoe, K.; Yasumizu, R.; Oh-Ishi, T.; Kakinuma, M.; Good, R.A.; Morikawa, K.

1981-01-01

Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient

Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Styczynski, Jan; Tridello, Gloria; Gil, Lidia; Ljungman, Per; Hoek, Jennifer; Iacobelli, Simona; Ward, Katherine N; Cordonnier, Catherine; Einsele, Hermann; Socie, Gerard; Milpied, Noel; Veelken, Hendrik; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Maertens, Johan; Blaise, Didier; Cornelissen, Jan; Michallet, Mauricette; Daguindau, Etienne; Petersen, Eefke; Passweg, Jakob; Greinix, Hildegard; Duarte, Rafael F; Kröger, Nicolaus; Dreger, Peter; Mohty, Mohamad; Nagler, Arnon; Cesaro, Simone

2016-07-01

We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P donors did not have an increased risk of GVHD. Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT. © 2016 by American Society of Clinical Oncology.

Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells

International Nuclear Information System (INIS)

Joysey, H.S.; Wakelin, D.; Rose, M.E.

1988-01-01

The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to infection with this parasite is expressed through bone-marrow-derived cells

Characterization of hemopoietic stem cell chimerism in antibody-facilitated bone marrow chimeras

International Nuclear Information System (INIS)

Francescutti, L.H.; Gambel, P.; Wegmann, T.G.

1985-01-01

The authors have previously described a model for bone marrow transplantation that involves preparation of the host with monoclonal antibody against class I or class II antigens instead of irradiation or cytotoxic drugs. This allows engraftment and subsequent repopulation of the host by donor tissue. They have previously reported on chimerism in the peripheral blood of P1----(P1 X P2)F1 animals. In this report, the authors describe the examination of the bone marrow and spleen stem cell chimerism of these antibody-facilitated (AF) chimeras, by determining, with an isozyme assay, the phenotype of methylcellulose colonies grown from stem cells. They have found a correlation between peripheral blood chimerism and the stem cell constitution of both spleen and bone marrow. The peripheral blood chimerism also correlates with the level of chimerism in macrophages derived from peritoneal exudate cells. These findings indicate that assaying the peripheral blood of such chimeras provides an excellent indication of the degree of chimerism at the stem cell level and stands in sharp contrast to the level of chimerism in certain lymphoid compartments

Circulating endothelial progenitor cell numbers are not associated with donor organ age or allograft vasculopathy in cardiac transplant recipients.

Science.gov (United States)

Thomas, H E; Parry, G; Dark, J H; Arthur, H M; Keavney, B D

2009-02-01

Increasing age is associated with reduced numbers of circulating endothelial progenitor cells (EPCs). It is unclear whether this relates to depletion or impairment of bone marrow progenitors, or to deficient mobilization signals from aging tissues. In cardiac transplant patients, one previous study has reported an association between circulating EPCs and the risk of cardiac allograft vasculopathy (CAV). We investigated whether increased donor heart age, a strong risk factor for CAV, was associated with reduced circulating EPC numbers in a group of cardiac transplant recipients matched for factors which influence EPC numbers, but with maximally discordant donor heart ages. We identified 32 patient pairs, matched for factors known to influence EPC numbers, but who had discordant donor heart ages by at least 20 years. EPCs were quantified using flow cytometry for absolute counts of cells expressing all the combinations of CD45, CD34, CD133 and the kinase domain receptor (KDR). There were no significant differences in the numbers of circulating EPCs between patients with old or young donor heart age. There was no association between the presence of CAV and circulating EPC numbers. We suggest that the increased susceptibility to CAV of older donor hearts is not mediated via circulating EPCs. Our results are consistent with the theory that the normal age-related decline in EPC numbers relates to bone marrow aging rather than failure of target tissues to induce EPC mobilization.

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

Science.gov (United States)

Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

2006-08-01

Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green

Donor transplant programme

International Nuclear Information System (INIS)

Abu Bakar Sulaiman

1999-01-01

The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

eRegistries: Electronic registries for maternal and child health.

Science.gov (United States)

Frøen, J Frederik; Myhre, Sonja L; Frost, Michael J; Chou, Doris; Mehl, Garrett; Say, Lale; Cheng, Socheat; Fjeldheim, Ingvild; Friberg, Ingrid K; French, Steve; Jani, Jagrati V; Kaye, Jane; Lewis, John; Lunde, Ane; Mørkrid, Kjersti; Nankabirwa, Victoria; Nyanchoka, Linda; Stone, Hollie; Venkateswaran, Mahima; Wojcieszek, Aleena M; Temmerman, Marleen; Flenady, Vicki J

2016-01-19

The Global Roadmap for Health Measurement and Accountability sees integrated systems for health information as key to obtaining seamless, sustainable, and secure information exchanges at all levels of health systems. The Global Strategy for Women's, Children's and Adolescent's Health aims to achieve a continuum of quality of care with effective coverage of interventions. The WHO and World Bank recommend that countries focus on intervention coverage to monitor programs and progress for universal health coverage. Electronic health registries - eRegistries - represent integrated systems that secure a triple return on investments: First, effective single data collection for health workers to seamlessly follow individuals along the continuum of care and across disconnected cadres of care providers. Second, real-time public health surveillance and monitoring of intervention coverage, and third, feedback of information to individuals, care providers and the public for transparent accountability. This series on eRegistries presents frameworks and tools to facilitate the development and secure operation of eRegistries for maternal and child health. In this first paper of the eRegistries Series we have used WHO frameworks and taxonomy to map how eRegistries can support commonly used electronic and mobile applications to alleviate health systems constraints in maternal and child health. A web-based survey of public health officials in 64 low- and middle-income countries, and a systematic search of literature from 2005-2015, aimed to assess country capacities by the current status, quality and use of data in reproductive health registries. eRegistries can offer support for the 12 most commonly used electronic and mobile applications for health. Countries are implementing health registries in various forms, the majority in transition from paper-based data collection to electronic systems, but very few have eRegistries that can act as an integrating backbone for health

Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

International Nuclear Information System (INIS)

Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

1980-01-01

A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation

Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway.

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Mariotti, Jacopo; Foley, Jason; Ryan, Kaitlyn; Buxhoeveden, Nicole; Kapoor, Veena; Amarnath, Shoba; Fowler, Daniel H

2008-12-01

Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.

Organ Donor Registration Preferences among Hispanic Populations: Which Modes of Registration Have the Greatest Promise?

Science.gov (United States)

Siegel, Jason T.; Alvaro, Eusebio M.; Jones, Sara Pace

2005-01-01

There is little debate over Hispanics' need for viable organs. Although organ donor registries can potentially assist in alleviating this need, the U.S. Department of Health and Human Services (DHHS) has called on researchers to investigate methods to maximize such potential. This research effort answers the aforementioned call by surveying…

Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone.

Science.gov (United States)

Rahhal, Dina N; Xu, Hong; Huang, Wei-Chao; Wu, Shengli; Wen, Yujie; Huang, Yiming; Ildstad, Suzanne T

2009-09-27

Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

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Yiannis N Kallis

Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

International Nuclear Information System (INIS)

Skidmore, B.J.; Miller, L.S.

1978-01-01

A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 10 5 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

Establishment of an oocyte donor program. Donor screening and selection.

Science.gov (United States)

Quigley, M M; Collins, R L; Schover, L R

1991-01-01

IVF with donated oocytes, followed by embryo placement in the uterus of a recipient who has been primed with exogenous steroids, is a successful treatment for special cases of infertility. Preliminary results indicate that the success rate in this situation is even greater than that usually seen with normal IVF (with placement of the embryos back into the uteri of the women from whom the oocytes were recovered). Although different sources for donated oocytes have been identified, the use of "excess" oocytes from IVF cycles and the attempted collection of oocytes at the time of otherwise indicated pelvic surgery have ethical and practical problems associated with their use. We have herein described the establishment of a successful program relying on anonymous volunteers who go through ovarian stimulation, monitoring, and oocyte recovery procedures solely to donate oocytes. The potential donors go through an exhaustive screening and education process before they are accepted in the program. Psychological evaluation of our potential donors indicated a great degree of turmoil in their backgrounds and a wide variety of motivations for actually participating. Despite the extensive educational and screening process, a substantial percentage of the donors did not complete a donation cycle, having either voluntarily withdrawn or been dropped because of lack of compliance. Further investigation of the psychological aspects of participating in such a program is certainly warranted. The use of donated oocytes to alleviate specific types of infertility is quite successful, but the application of this treatment is likely to be limited by the relative unavailability of suitable oocyte donors.

Role of bone marrow transplantation for correcting hemophilia A in mice

Science.gov (United States)

Follenzi, Antonia; Raut, Sanj; Merlin, Simone; Sarkar, Rita

2012-01-01

To better understand cellular basis of hemophilia, cell types capable of producing FVIII need to be identified. We determined whether bone marrow (BM)–derived cells would produce cells capable of synthesizing and releasing FVIII by transplanting healthy mouse BM into hemophilia A mice. To track donor-derived cells, we used genetic reporters. Use of multiple coagulation assays demonstrated whether FVIII produced by discrete cell populations would correct hemophilia A. We found that animals receiving healthy BM cells survived bleeding challenge with correction of hemophilia, although donor BM-derived hepatocytes or endothelial cells were extremely rare, and these cells did not account for therapeutic benefits. By contrast, donor BM-derived mononuclear and mesenchymal stromal cells were more abundant and expressed FVIII mRNA as well as FVIII protein. Moreover, injection of healthy mouse Kupffer cells (liver macrophage/mononuclear cells), which predominantly originate from BM, or of healthy BM-derived mesenchymal stromal cells, protected hemophilia A mice from bleeding challenge with appearance of FVIII in blood. Therefore, BM transplantation corrected hemophilia A through donor-derived mononuclear cells and mesenchymal stromal cells. These insights into FVIII synthesis and production in alternative cell types will advance studies of pathophysiological mechanisms and therapeutic development in hemophilia A. PMID:22368271

Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology.

Science.gov (United States)

Yeh, Jason S; Steward, Ryan G; Dude, Annie M; Shah, Anish A; Goldfarb, James M; Muasher, Suheil J

2014-05-01

To use a large and recent national registry to provide an updated report on the effect of recipient age on the outcome of donor oocyte in vitro fertilization (IVF) cycles. Retrospective cohort study. United States national registry for assisted reproductive technology. Recipients of donor oocyte treatment cycles between 2008 and 2010, with cycles segregated into five age cohorts: ≤34, 35 to 39, 40 to 44, 45 to 49, and ≥50 years. None. Implantation, clinical pregnancy, live-birth, and miscarriage rates. In donor oocyte IVF cycles, all age cohorts ≤39 years had similar rates of implantation, clinical pregnancy, and live birth when compared with the 40- to 44-year-old reference group. Patients in the two oldest age groups (45 to 49, ≥50 years) experienced statistically significantly lower rates of implantation, clinical pregnancy, and live birth compared with the reference group. Additionally, all outcomes in the ≥50-year-old group were statistically significantly worse than the 45- to 49-year-old group, demonstrating progressive decline with advancing age. Recent national registry data suggest that donor oocyte recipients have stable rates of pregnancy outcomes before age 45, after which there is a small but steady and significant decline. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

Science.gov (United States)

Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

2003-01-01

There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

Science.gov (United States)

Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

2014-01-01

Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45−/14−). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10−7 M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10−6 M (Group 1, A), 10−5 M (Group 2, B), 10−4 M (Group 3, A/B), and together with 10−7 M iloprost (Groups 4–6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34−, CD45−, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). Results Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. Conclusions Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin

Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study

International Nuclear Information System (INIS)

Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Hitomi, K.; Utsuyama, M.

1985-01-01

Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

Science.gov (United States)

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

Directory of Open Access Journals (Sweden)

Raphael P H Meier

Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

Starvation marrow – gelatinous transformation of bone marrow

Directory of Open Access Journals (Sweden)

Eric Osgood

2014-09-01

Full Text Available Gelatinous bone marrow transformation (GMT, also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

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Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both pbones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

EMI Registry Design

CERN Document Server

Memon, S

2011-01-01

Grid services are the fundamental building blocks of today's Distributed Computing Infrastructures (DCI). The discovery of services in the DCI is a primary function that is a precursor to other tasks such as workload and data management. In this context, a service registry can be used to fulfil such a requirement. Existing service registries, such as the ARC Information Index or UNICORE Registry, are examples that have proven themselves in production environments. Such implementations provide a centralized service registry, however, todays DCIs, such as EGI, are based on a federation model. It is therefore necessary for the service registry to mirror such a model in order for it to seamlessly fit into the operational and management requirements - a DCI built using federated approach. This document presents an architecture for a federated service registry and a prototype based on this architecture, the EMI Registry. Special attention is given to how the federated service registry is robust to environment failu...

T-cell depleted haploidentical three loci mismatched bone-marrow and peripheral blood stem cell transplantation in acute leukaemia patients

International Nuclear Information System (INIS)

Aristei, C.; Aversa, F.; Panizza, B.M.; Perrucci, E.; Barone, V.; Marafioti, L.; Raymondi, C.; Terenzi, A.; Martelli, M.F.; Latini, P.

1996-01-01

Objectives: Allogeneic bone-marrow transplantation (BMT) is an established treatment for many haematological malignancies. Unfortunately, most patients lack an HLA geno typically identical sibling and require an alternative donor, such as an HLA-haploidentical mismatched related donor, an HLA phenotypically matched or partially mismatched unrelated donor or an HLA-similar cord blood stem cell donor. However, these types of BMT increase the risk of graft-versus-host disease (GvHD), graft failure, delayed immuno reconstitution and fatal infection that observed after a sibling matched donor. Many centers are exploring the possibility of using donors other than matched sibling. Our approach has been to employ T-cell depleted mismatched haploidentical familial donor BMT to solve the problem of GvHD, a highly immuno- and myelo-suppressive conditioning regimen to reduce the incidence of graft failure and relapse, a graft inoculum plus G-CSF donor mobilized peripheral blood stem cells (PBSC) to overcome the host-versus-graft barrier. Patients and methods: Thirty-six patients (25 male, 11 female; median age 22 years, range 2-51) were treated with an allogeneic T-depleted haploidentical three loci mismatched bone-marrow and G-CSF mobilized PBSC transplantation from a familiar donor (18 siblings, 17 parents and 1 cousin) between March 1993 and June 1995. All had high-risk or advanced stage acute myeloid (12) or acute lymphoid (24) leukaemia; 18 were in haematological complete remission (CR) and 18 in chemo resistant relapse. Patients were conditioned with 8 Gy single dose TBI administered on day -5 at an instantaneous dose-rate of 13.4-31.7 cGy/min/midplane and average of 6.7-12.12 cGy/min/midplane. Shields were used to reduce the lung dose to 7 Gy in the first 23 cases and to 6 Gy in the last 13. 10 mg/Kg thiotepa were administered on day -4, 5 mg/Kg rabbit ATG from day -4 to day -1, 60 or 50 mg/Kg/cyclophosphamide on days -3 and -2. Bone-marrow and PBSC were infused on day

Differences in social representation of blood donation between donors and non-donors: an empirical study.

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Guarnaccia, Cinzia; Giannone, Francesca; Falgares, Giorgio; Caligaris, Aldo Ozino; Sales-Wuillemin, Edith

2015-11-04

Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. Participants filled in the Adapted Self-Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non-donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non-donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments.

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation.

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Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

2014-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor. The aim was to explore patients' experiences, immediately before transplantation, regarding having a sibling as donor. Ten adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being in no man's land is a metaphor for the patients' complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient's experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor's safety during donation. These emotions intensify the patients' sense of dependency and loss of control. In caring for HSCT patients the nurses should be aware of the complexity of the patients' situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

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Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

The Kinetic Family Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

Science.gov (United States)

Packman, Wendy L.; Crittenden, Mary R.; Fischer, Jodie B. Rieger; Cowan, Morton J.; Long, Janet K.; Gruenert, Carol; Schaeffer, Evonne; Bongar, Bruce

1998-01-01

Utilizes the Kinetic Family Drawings-Revised (KFD-R) to measure siblings' (N=44) feelings and attitudes toward bone marrow transplants. Data from drawings and discussions with siblings underscore that not all children are affected by stress in the same way. How a particular child responds depends on factors such as life history, personality,…

Automated processing of human bone marrow can result in a population of mononuclear cells capable of achieving engraftment following transplantation.

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Areman, E M; Cullis, H; Spitzer, T; Sacher, R A

1991-10-01

A concentrate of mononuclear bone marrow cells is often desired for ex vivo treatment with pharmacologic agents, monoclonal antibodies, cytokines, and other agents prior to transplantation. A method has been developed for automated separation of mononuclear cells from large volumes of harvested bone marrow. A programmable instrument originally designed for clinical ex vivo cell separation and the plasma-pheresis of patients and blood donors was adapted to permit rapid preparation, in a closed sterile system, of a bone marrow product enriched with mononuclear cells. A mean (+/- SEM) of 53 +/- 30 percent of the original mononuclear cells was recovered in a volume of 125 +/- 42 mL containing 82 +/- 12 percent mononuclear cells. This technique removed 95 +/- 9 percent of the red cells in the original marrow. No density gradient materials or sedimenting agents were employed in this process. Of 36 marrows processed by this technique, 19 autologous (6 of which were purged with 4-hydroperoxycyclophosphamide) and 7 allogeneic marrows have been transplanted, with all evaluable patients achieving a neutrophil count of 0.5 x 10(9) per L in a mean (+/- SEM) of 21 +/- 6 days.

Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

International Nuclear Information System (INIS)

Breathnach, S.M.; Katz, S.I.

1984-01-01

Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes

Summary of data held by the National Registry for Radiation Workers

CERN Document Server

Kendall, G M; O'Hagen, J A; Rees, S; Walker, S M

1988-01-01

This report summarises the data held by the National Registry for Radiation Workers at the end of 1985. Agreement has been reached with the participating organisations for transfer of records on 97,000 individuals. However, some individuals have been employed by more than one participating organisation and a few (2%) have refused to participate, so the final study population will be somewhat smaller. Over 95% of participants have been registered and arrangements are in hand to include most of the remainder. Although some information is still outstanding, there has been a considerable improvement since the publication of the second supplement to NRPB-R116 (Protocol for the National Registry for Radiation Workers) which described the database at the end of 1983. Details are given for each of the participating organisations.

Pathological changes after bone marrow and skin allograft transplantation in rats inflicted with severe combined radiation-burn injury

International Nuclear Information System (INIS)

Zheng Huaien; Cheng Tianmin; Yan Yongtang

1994-01-01

Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

ISHKS joint registry: A preliminary report

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Jawahir A Pachore

2013-01-01

form can be downloaded from the website www.ishks.com. The information collected includes patient demographics, indication for surgery, implant details and in case of revision arthroplasty: the details of implants removed and the cause of failure of primary arthroplasty. These forms are mailed to the central registry office and the data is fed in computerized registry. Data collection started in October 2006. Results: Joint registry is a very important initiative of ISHKS and till date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across India. Some important observations have emerged. Data of 34,478 TKAs was assessed: These included 8612 males (25% and 25,866 females (75%. Average age was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range: 22 to 74 years. Average body mass index was 29.1 (Range: 18.1 to 42.9. The indication for TKA was osteoarthritis in 33,444 (97% and rheumatoid arthritis in 759 (2.2%. Total of 3604 THA procedures were recorded. These included 2162 (60% male patients and 1442 (40% female patients. Average age was 52 years (Range 17 to 85 years and average BMI was 25.8 (Range: 17.3 to 38.5. The indications for THA was AVN in 49%. Conclusion: The registry will become more meaningful in years to come. Active participation of all arthroplasty surgeons across India is vital for the success of the joints registry.

Effects Of Hypoxia in Long-Term In Vitro Expansion of Human Bone Marrow Derived Mesenchymal Stem Cells.

Science.gov (United States)

Pezzi, Annelise; Amorin, Bruna; Laureano, Álvaro; Valim, Vanessa; Dahmer, Alice; Zambonato, Bruna; Sehn, Filipe; Wilke, Ianaê; Bruschi, Lia; Silva, Maria Aparecida Lima da; Filippi-Chiela, Eduardo; Silla, Lucia

2017-10-01

Mesenchymal stem cells (MSC) are considered multipotent stromal, non-hematopoietic cells with properties of self-renovation and differentiation. Optimal conditions for culture of MSC have been under investigation. The oxygen tension used for cultivation has been studied and appears to play an important role in biological behavior of mesenchymal cells. The aim is characterize MSC in hypoxia and normoxia conditions comparing their morphological and functional characteristics. Bone marrow-derived mesenchymal stem cells obtained from 15 healthy donors and cultured. MSC obtained from each donor were separated into two cultivation conditions normoxia (21% O 2 ) and hypoxia (three donors at 1%, three donors at 2%, five donors at 3%, and four donors at 4% O 2 ) up to second passage. MSC were evaluated for proliferation, differentiation, immunophenotyping, size and cell complexity, oxidative stress, mitochondrial activity, and autophagy. Culture conditions applied did not seem to affect immunophenotypic features and cellular plasticity. However, cells subjected to hypoxia showed smaller size and greater cellular complexity, besides lower proliferation (P cells cultured in low O 2 tension had lower mitochondrial activity (P Cell. Biochem. 118: 3072-3079, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

EFFECT ON LIFESPAN OF HIGH YIELD NONMYELOABLATING TRANSPLANTATION OF BONE MARROW FROM YOUNG TO OLD MICE

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Marina eKovina

2013-08-01

Full Text Available Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SC. An interesting question is whether donor stem cells are capable to prolong the lifespan of an ageing organism by tissue renewal.. In this work we investigated the possible use of bone marrow SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting bone marrow from young 1.5-month donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5×108 cells, that is, about 25 % of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (± 0.1 months for the control and experimental groups, respectively, corresponding to a 39% ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation a considerably smaller quantity of donor cells (5×106 was used, about 1 % of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals X-ray dose which eliminated the possibility of studying the lifespan extension by this method.

The long and the short of telomeres in bone marrow recipient SCID patients

OpenAIRE

Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G.; Whitesides, John F.; Buckley, Rebecca H.

2011-01-01

Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant’s vestigial thymus and to homeostatic proliferation...

Adoption and implementation of mandated diabetes registries by community health centers.

Science.gov (United States)

Helfrich, Christian D; Savitz, Lucy A; Swiger, Kathleen D; Weiner, Bryan J

2007-07-01

Innovations adopted by healthcare organizations are often externally mandated. However, few studies examine how mandated innovations progress from adoption to sustained effective use. This study uses Rogers's model of organizational innovation to explore community health centers' (CHCs') mandated adoption and implementation of disease registries in the federal Health Disparities Collaborative (HDC). Case studies were conducted on six CHCs in North Carolina participating in the HDC on type 2 diabetes mellitus. Data were collected from semistructured interviews with key staff, and from site-level and individual-level surveys. Although disease registry adoption and implementation were mandated, CHCs exercised prerogative in the timing of registry adoption and the functions emphasized. Executive and medical director involvement, often directly on the HDC teams, was the single most salient influence on adoption and implementation. Staff members' personal experience with diabetes also provided context and gave registries added significance. Participants lauded HDC's technique of small-scale, rapid-cycle change, but valued even more shared problem solving and peer learning among HDC teams. However, lack of cross-training, inadequate resources, and staff turnover posed serious threats to sustainability of the registries. The present study illustrates the usefulness of Rogers's model for studying mandated innovation and highlights several key factors, including direct, personal involvement of organizational leadership, and shared problem solving and peer learning facilitated by the HDC. However, these six CHCs elected to participate early in the HDC, and may not be typical of North Carolina's remaining CHCs. Furthermore, most face important long-term challenges that threaten routinization.

Transfer of innate resistance and susceptibility to Leishmania donovani infection in mouse radiation bone marrow chimaeras

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Crocker, P.R.; Blackwell, J.M.; Bradley, D.J. (London School of Hygiene and Tropical Medicine (UK))

1984-07-01

Reciprocal radiation bone marrow chimaeras were made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshsup(r) and Lshsup(s) alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. It is concluded that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage.

Transfer of innate resistance and susceptibility to Leishmania donovani infection in mouse radiation bone marrow chimaeras

International Nuclear Information System (INIS)

Crocker, P.R.; Blackwell, J.M.; Bradley, D.J.

1984-01-01

Reciprocal radiation bone marrow chimaeras mere made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshsup(r) and Lshsup(s) alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. It is concluded that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage. (author)

Support for immunization registries among parents of vaccinated and unvaccinated school-aged children: a case control study

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Pan William KY

2006-09-01

Full Text Available Abstract Background Immunizations have reduced childhood vaccine preventable disease incidence by 98–100%. Continued vaccine preventable disease control depends on high immunization coverage. Immunization registries help ensure high coverage by recording childhood immunizations administered, generating reminders when immunizations are due, calculating immunization coverage and identifying pockets needing immunization services, and improving vaccine safety by reducing over-immunization and providing data for post-licensure vaccine safety studies. Despite substantial resources directed towards registry development in the U.S., only 48% of children were enrolled in a registry in 2004. Parental attitudes likely impact child participation. Consequently, the purpose of this study was to assess the attitudes of parents of vaccinated and unvaccinated school-aged children regarding: support for immunization registries; laws authorizing registries and mandating provider reporting; opt-in versus opt-out registry participation; and financial worth and responsibility of registry development and implementation. Methods A case control study of parents of 815 children exempt from school vaccination requirements and 1630 fully vaccinated children was conducted. Children were recruited from 112 elementary schools in Colorado, Massachusetts, Missouri, and Washington. Surveys administered to the parents, asked about views on registries and perceived utility and safety of vaccines. Parental views were summarized and logistic regression models compared differences between parents of exempt and vaccinated children. Results Surveys were completed by 56.1% of respondents. Fewer than 10% of parents were aware of immunization registries in their communities. Among parents aware of registries, exempt children were more likely to be enrolled (65.0% than vaccinated children (26.5% (p value = 0.01. A substantial proportion of parents of exempt children support immunization

Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Cesaro, Simone; Peffault de Latour, Regis; Tridello, Gloria; Pillon, Marta; Carlson, Kristina; Fagioli, Franca; Jouet, Jean-Pierre; Koh, Mickey B C; Panizzolo, Irene Sara; Kyrcz-Krzemien, Slawomira; Maertens, Johan; Rambaldi, Alessandro; Strahm, Brigitte; Blaise, Didier; Maschan, Alexei; Marsh, Judith; Dufour, Carlo

2015-11-01

We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17 days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3·5 years, the 5-year overall survival (OS) was 60·7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score ≥80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases. © 2015 John Wiley & Sons Ltd.

Data mining of mental health issues of non-bone marrow donor siblings.

Science.gov (United States)

Takita, Morihito; Tanaka, Yuji; Kodama, Yuko; Murashige, Naoko; Hatanaka, Nobuyo; Kishi, Yukiko; Matsumura, Tomoko; Ohsawa, Yukio; Kami, Masahiro

2011-07-20

Allogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis. A 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family. This single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

Proliferation differentiation and therapeutic effect of short-term cultured murine bone marrow cells

International Nuclear Information System (INIS)

Zhao Zekun; Cong Jianbo

1986-01-01

Murine bone marrow cells were cultured in conditioned medium of muscle. After 24 hours of culture, both adherent and suspended cells appeared in the culture. The adherent cells mainly consisted of macrophages and the suspended cells were predominantly granulocytes. After 6 days, the total number of nucleated cells and CFU-C in the culture increased about 400% and 600% respectively, but CFU-S reduced to 21% approximately. Lymphocytes persisted only for 4 days. The stem cells (CFU-S) from 6-day culture were injected into the lethally irradiated syngenic mice. The 30 day survival rate of the treated mice was 89% whereas that of the controls was only 7%. The bone marrow cells in 2/8 of recipients sacrificed at 30 or 60 days were of donor type and 6/8 of the recipients were chimeras

Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

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Brend Ray-Sea Hsu

2017-01-01

Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: Effect on bone marrow microenvironment.

Directory of Open Access Journals (Sweden)

Soraya Carrancio

Full Text Available The aim of the present study was to determine how mesenchymal stem cells (MSC could improve bone marrow (BM stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34(+ progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin, involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (i.v. or intrabone (i.b. route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

Science.gov (United States)

Adams, Zachary; Morris, Gail; Campbell, Todd; Mostert, Karen; Dibdin, Nicholas; Fearon, Margaret; Elmoazzen, Heidi; Mercer, Dena; Young, Kimberly; Allan, David

2018-04-01

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The association of IgA deficiency on infection rate, self-perceived health, and levels of C-reactive protein in healthy blood donors

DEFF Research Database (Denmark)

Hauge, Sabina Chaudhary; Jensen, Charlotte Kæstel; Nielsen, Leif Kofoed

2018-01-01

The clinical importance of immunoglobulin A (IgA) deficiency in otherwise healthy individuals is not well described. We aimed to investigate the self-reported mental and physical health and the risk of infection in IgA-deficient blood donors compared to healthy control blood donors. Infectious...... events, recorded in public health registries either as prescriptions filled of any antimicrobial medicine or as hospital infections, were compared between 177 IgA-deficient blood donors and 1770 control blood donors. A subset of the IgA-deficient donors were further characterized by self-reported health...... was found with hospital infections (hazard ratio = 1.02, p = 0.95) or self-reported physical health (p = 0.86). IgA-deficient blood donors have impaired self-reported mental health, enhanced inflammation and possibly an increased risk of infection. Despite these findings, this study does not provide...

United States transuranium and uranium registries - 25 years of growth, research, and service. Annual report, April 1992--September 1993

International Nuclear Information System (INIS)

Kathren, R.L.; Harwick, L.A.; Toohey, R.E.; Russell, J.J.; Filipy, R.E.; Dietert, S.E.; Hunacek, M.M.; Hall, C.A.

1994-01-01

The Registries originated in 1968 as the National Plutonium Registry with the name changed to the United States Transuranium Registry the following year to reflect a broader concern with the heavier actinides as well. Initially, the scientific effort of the USTR was directed towards study of the distribution and dose of plutonium and americium in occupationally exposed persons, and to assessment of the effects of exposure to the transuranium elements on health. This latter role was reassessed during the 1970's when it was recognized that the biased cohort of the USTR was inappropriate for epidemiologic analysis. In 1978, the administratively separate but parallel United States Uranium Registry was created to carry out similar work among persons exposed to uranium and its decay products. A seven member scientific advisory committee provided guidance and scientific oversight. In 1992, the two Registries were administratively combined and transferred from the purview of a Department of Energy contractor to Washington State University under the provisions of a grant. Scientific results for the first twenty-five years of the Registries are summarized, including the 1985 publication of the analysis of the first whole body donor. Current scientific work in progress is summarized along with administrative activities for the period

United States transuranium and uranium registries - 25 years of growth, research, and service. Annual report, April 1992--September 1993

Energy Technology Data Exchange (ETDEWEB)

Kathren, R.L.; Harwick, L.A.; Toohey, R.E.; Russell, J.J.; Filipy, R.E.; Dietert, S.E.; Hunacek, M.M.; Hall, C.A.

1994-10-01

The Registries originated in 1968 as the National Plutonium Registry with the name changed to the United States Transuranium Registry the following year to reflect a broader concern with the heavier actinides as well. Initially, the scientific effort of the USTR was directed towards study of the distribution and dose of plutonium and americium in occupationally exposed persons, and to assessment of the effects of exposure to the transuranium elements on health. This latter role was reassessed during the 1970`s when it was recognized that the biased cohort of the USTR was inappropriate for epidemiologic analysis. In 1978, the administratively separate but parallel United States Uranium Registry was created to carry out similar work among persons exposed to uranium and its decay products. A seven member scientific advisory committee provided guidance and scientific oversight. In 1992, the two Registries were administratively combined and transferred from the purview of a Department of Energy contractor to Washington State University under the provisions of a grant. Scientific results for the first twenty-five years of the Registries are summarized, including the 1985 publication of the analysis of the first whole body donor. Current scientific work in progress is summarized along with administrative activities for the period.

Postirradiation bone marrow damage in chickens

International Nuclear Information System (INIS)

Skardova, I.; Ojeda, F.

1994-01-01

The frequency of bone marrow damage induced by the continuous gamma irradiation was studied. Effect of dose rate and level of cumulated doses of radiation was evaluated in clinical and hematological examinations and bone marrow damage was determined by chromosome aberrations in anaphase. The regulative ability of hematopoiesis of many cytokines are discussed. Positive regulators are inducers of cell proliferation, and negative regulators are inducers of apoptosis /programmed cell death/. Birds corresponding with similarities in thymus-T and bursal-B cells appear to be an interesting model for studying the possible participation of apoptosis in radiation disease. Our recent experimental studies continue to progress in this direction. (author) 17 refs.; 3 figs.; 2 tabs

Windows registry forensics advanced digital forensic analysis of the Windows registry

CERN Document Server

Carvey, Harlan

2011-01-01

Harlan Carvey brings readers an advanced book on Windows Registry - the most difficult part of Windows to analyze in forensics! Windows Registry Forensics provides the background of the Registry to help develop an understanding of the binary structure of Registry hive files. Approaches to live response and analysis are included, and tools and techniques for postmortem analysis are discussed at length. Tools and techniques will be presented that take the analyst beyond the current use of viewers and into real analysis of data contained in the Registry. This book also has a DVD containing tools, instructions and videos.

Acquisition of vernal and atopic keratoconjunctivitis after bone marrow transplantation.

Science.gov (United States)

Tabbara, Khalid F; Nassar, Amr; Ahmed, Syed Osman; Al Mohareb, Fahad; Aljurf, Mahmoud

2008-09-01

Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) result from genetic and environmental factors. We present patients who had no history of atopic disorders before bone marrow transplantation (BMT) and who seem to have acquired VKC or AKC from their donors, who had atopic disorders. Observational case series. The patients in this study were part of a cohort of patients who had undergone allogeneic hemapoietic stem cell transplantation (HSCT) from January 1997 through December 2007. Of 621 HSCT recipients, four recipients who were free of allergic disorders acquired VKC or AKC from their afflicted donors after HSCT. Each patient underwent complete ophthalmologic examination, determination of the total serum immunoglobulin (Ig) E, and conjunctival scrapings. Four (0.64%) of 621 patients who had undergone HSCT acquired VKC or AKC after BMT. The donors had VKC or atopic dermatitis. In addition, in two of these four patients, asthma developed. One patient had elevated total serum IgE. Conjunctival scrapings of all four patients revealed the presence of eosinophils. One patient had concurrent graft-versus-host disease. VKC and AKC are systemic allergic disorders characterized by local ocular manifestations. This report suggests the possibility of the acquisition of VKC or AKC after BMT by adoptive transfer.

The effect of cyclic hydrostatic pressure on the functional development of cartilaginous tissues engineered using bone marrow derived mesenchymal stem cells.

Science.gov (United States)

Meyer, E G; Buckley, C T; Steward, A J; Kelly, D J

2011-10-01

Mechanical signals can play a key role in regulating the chondrogenic differentiation of mesenchymal stem cells (MSCs). The objective of this study was to determine if the long-term application of cyclic hydrostatic pressure could be used to improve the functional properties of cartilaginous tissues engineered using bone marrow derived MSCs. MSCs were isolated from the femora of two porcine donors, expanded separately under identical conditions, and then suspended in cylindrical agarose hydrogels. Constructs from both donors were maintained in a chemically defined media supplemented with TGF-β3 for 42 days. TGF-β3 was removed from a subset of constructs from day 21 to 42. Loaded groups were subjected to 10 MPa of cyclic hydrostatic pressurisation at 1 Hz for one hour/day, five days/week. Loading consisted either of continuous hydrostatic pressure (CHP) initiated at day 0, or delayed hydrostatic pressure (DHP) initiated at day 21. Free swelling (FS) constructs were cultured in parallel as controls. Constructs were assessed at days 0, 21 and 42. MSCs isolated from both donors were morphologically similar, demonstrated comparable colony forming unit-fibroblast (CFU-F) numbers, and accumulated near identical levels of collagen and GAG following 42 days of free swelling culture. Somewhat unexpectedly the two donors displayed a differential response to hydrostatic pressure. For one donor the application of CHP resulted in increased collagen and GAG accumulation by day 42, resulting in an increased dynamic modulus compared to FS controls. In contrast, CHP had no effect on matrix accumulation for the other donor. The application of DHP had no effect on either matrix accumulation or construct mechanical properties for both donors. Variability in the response to hydrostatic pressure was also observed for three further donors. In conclusion, this study demonstrates that the application of long-term hydrostatic pressure can be used to improve the functional properties of

The Psychosocial and Independent Living Donor Advocate Evaluation and Post-surgery Care of Living Donors.

Science.gov (United States)

Rudow, Dianne LaPointe; Swartz, Kathleen; Phillips, Chelsea; Hollenberger, Jennifer; Smith, Taylor; Steel, Jennifer L

2015-09-01

Solid organ transplantation as a treatment for end stage organ failure has been an accepted treatment option for decades. Despite advances in medicine and technology, and increased awareness of organ donation and transplantation, the gap between supply and demand continues to widen. Living donation has been an option that has increased the number of transplants despite the continued shortage of deceased organs. In the early 2000s live donor transplantation reached an all-time high in the United States. As a result, a consensus meeting was convened in 2000 to increase the oversight of living donor transplantation. Both the Centers for Medicare and Medicaid Services and the United Network for Organ Sharing developed regulations that transplant programs performing live donor transplantation. These regulations and guidelines involve the education, evaluation, informed consent process and living donor follow-up care. Two areas in which had significant changes included the psychosocial and the independent living donor advocate (ILDA) evaluation. The purpose of this paper was to outline the current regulations and guidelines associated with the psychosocial and ILDA evaluation as well as provide further recommendations for the administration of a high quality evaluation of living donors. The goals and timing of the evaluation and education of donors; qualifications of the health care providers performing the evaluation; components of the evaluation; education provided to donors; documentation of the evaluation; participation in the selection committee meeting; post-decline and post-donation care of donors is described. Caveats including the paired donor exchange programs and non-directed and directed donation are also considered.

Optimal use of MRI in clinical trials, clinical care and clinical registries of patients with rheumatoid arthritis

DEFF Research Database (Denmark)

Østergaard, Mikkel; Møller-Bisgaard, Signe

2014-01-01

the benefits of including MRI in treat-to-target strategies. The benefits of incorporating MRI into clinical registries are not yet known, but may include improved knowledge about the real-life advantages of MRI, as well as opportunities to develop better clinical and laboratory composite measures to monitor......Magnetic resonance imaging (MRI) clearly is more sensitive than clinical examination and conventional radiography (x-ray) for detection of inflammation (synovitis, bone marrow oedema (osteitis) and tenosynovitis) and damage (bone erosion and cartilage loss/joint space narrowing) in patients...... with rheumatoid arthritis (RA). The question is when and how MRI should be used. The present article reviews our knowledge about, and provides suggestions for, the use of MRI in clinical trials, clinical care and clinical registries. In clinical trials, the OMERACT RA MRI scoring system (RAMRIS) is a thoroughly...

Ethical aspects of registry-based research in the Nordic countries.

Science.gov (United States)

Ludvigsson, Jonas F; Håberg, Siri E; Knudsen, Gun Peggy; Lafolie, Pierre; Zoega, Helga; Sarkkola, Catharina; von Kraemer, Stephanie; Weiderpass, Elisabete; Nørgaard, Mette

2015-01-01

National health care registries in the Nordic countries share many attributes, but different legal and ethical frameworks represent a challenge to promoting effective joint research. Internationally, there is a lack of knowledge about how ethical matters are considered in Nordic registry-based research, and a lack of knowledge about how Nordic ethics committees operate and what is needed to obtain an approval. In this paper, we review ethical aspects of registry-based research, the legal framework, the role of ethics review boards in the Nordic countries, and the structure of the ethics application. We discuss the role of informed consent in registry-based research and how to safeguard the integrity of study participants, including vulnerable subjects and children. Our review also provides information on the different government agencies that contribute registry-based data, and a list of the major health registries in Denmark, Finland, Iceland, Norway, and Sweden. Both ethical values and conditions for registry-based research are similar in the Nordic countries. While Denmark, Finland, Iceland, Norway, and Sweden have chosen different legal frameworks, these differences can be resolved through mutual recognition of ethical applications and by harmonizing the different systems, likely leading to increased collaboration and enlarged studies.

Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013

DEFF Research Database (Denmark)

Fosby, Bjarte; Melum, Espen; Bjøro, Kristian

2015-01-01

AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage...

Bone marrow ablation with Ho-166 pharmaceuticals as preparation for bone marrow transplants

International Nuclear Information System (INIS)

Parks, N.J.; Kawakami, T.; Avila, M.; White, R.; Cain, G.; Moore, P.F.

1991-01-01

Bone marrow ablation is required preparation for leukemia patients where bone marrow transplantation is to be the therapeutic modality. Presently, the total body irradiation that is used produces appreciable morbidity in terms of radiation sickness, but an evenly distributed dose to marrow. The authors have shown in Beagles that bone-seeking radiolanthanide (Ho-166, t 1/2 = 25 h, 1.8 MeB beta, carrier added) phosphonic acid chelates can be used to completely ablate bone marrow with little morbidity. The research plan, incorporating bone marrow ablation with bone-seeking radionuclides and in vitro purging of aspirated leukemic marrow for use in autologous marrow transplants, is presented. Phosphonic acid complexes of Sm-153 also localize in the skeleton and have found use in the palliation of bone pain. However, the dose distribution is uneven because these radiopharmaceuticals distribute according to available surface; 2-4 times the skeletal average in trabecular vs cortical bone. Thus, the marrow dose can vary. The authors' research group and the Radiation Interactions Division of NIST have announced the discovery that beta radiation-induced excited electrons are trapped in the hydroxyapatite mineral of bone and provide a potential direct dosimetric method for marrow dose when combined with routine bone marrow (and included bone) biopsies. The overall research plan sets the hypothesis that reduced morbidity marrow ablation can be successfully followed by bone marrow transplantation (BMT) with autologous marrow purged in vitro by antibody-targeted alpha emitters

The Brazilian Twin Registry.

Science.gov (United States)

Ferreira, Paulo H; Oliveira, Vinicius C; Junqueira, Daniela R; Cisneros, Lígia C; Ferreira, Lucas C; Murphy, Kate; Ordoñana, Juan R; Hopper, John L; Teixeira-Salmela, Luci F

2016-12-01

The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

Science.gov (United States)

Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

2004-08-27

The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma

International Nuclear Information System (INIS)

Fonti, R.; Del Vecchio, S.; Zannetti, A.; Di Gennaro, F.; Pace, L.; Salvatore, M.; De Renzo, A.; Catalano, L.; Califano, C.; Rotoli, B.

2001-01-01

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99m Tc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99m Tc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99m Tc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99m Tc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99m Tc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P 99m Tc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments. (orig.)

Second generation registry framework.

Science.gov (United States)

Bellgard, Matthew I; Render, Lee; Radochonski, Maciej; Hunter, Adam

2014-01-01

Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage. This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised. We introduce the second generation RDRF that

The Mid-Atlantic Twin Registry, revisited.

Science.gov (United States)

Lilley, Emily C H; Silberg, Judy L

2013-02-01

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 56,000 twins primarily born or living in Virginia, North Carolina, and South Carolina. The MATR employs several methods of ascertaining twins, and devotes considerable resources to tracking and maintaining communication with MATR participants. Researchers may utilize the MATR for administration of research services including study recruitment, collection of DNA, archival data set creation, as well as data collection through mailed, phone, or online surveys. In addition, the MATR houses the MATR Repository, with over 1,200 blood samples available for researchers interested in DNA genotyping. For over 35 years MATR twins have participated in research studies with investigators from diverse scientific disciplines and various institutions. These studies, which have resulted in numerous publications, have covered a range of topics, including the human microbiome, developmental psychopathology, depression, anxiety, substance use, epigenetics of aging, children of twins, pre-term birth, social attitudes, seizures, eating disorders, as well as sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.

Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

Science.gov (United States)

Eichler, Hermann; Orth, Patrick

2017-01-01

Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

Mexican registry of pulmonary hypertension: REMEHIP.

Science.gov (United States)

Sandoval Zarate, Julio; Jerjes-Sanchez, Carlos; Ramirez-Rivera, Alicia; Zamudio, Tomas Pulido; Gutierrez-Fajardo, Pedro; Elizalde Gonzalez, Jose; Leon, Mario Seoane Garcia De; Gamez, Miguel Beltran; Abril, Francisco Moreno Hoyos; Michel, Rodolfo Parra; Aguilar, Humberto Garcia

REMEHIP is a prospective, multicentre registry on pulmonary hypertension. The main objective will be to identify the clinical profile, medical care, therapeutic trends and outcomes in adult and pediatric Mexican patients with well-characterized pulmonary hypertension. REMEHIP a multicenter registry began in 2015 with a planned recruitment time of 12 months and a 4-year follow-up. The study population will comprise a longitudinal cohort study, collecting data on patients with prevalent and incident pulmonary hypertension. Will be included patients of age >2 years and diagnosis of pulmonary hypertension by right heart catheterization within Group 1 and Group 4 of the World Health Organization classification. The structure, data collection and data analysis will be based on quality current recommendations for registries. The protocol has been approved by institutional ethics committees in all participant centers. All patients will sign an informed consent form. Currently in Mexico, there is a need of observational registries that include patients with treatment in the everyday clinical practice so the data could be validated and additional information could be obtained versus the one from the clinical trials. In this way, REMEHIP emerges as a link among randomized clinical trials developed by experts and previous Mexican experience. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2. The bone marrow distribution in leukemia

Energy Technology Data Exchange (ETDEWEB)

Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

1976-04-01

Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia.

Marrow uptake index (MUI): A quantitative scintigraphic study of bone marrow in aplastic anaemia

International Nuclear Information System (INIS)

Padhy, A.K.; Garg, A.; Kochupillai, V.; Gopinath, P.G.; Basu, A.K.

1987-01-01

Aplastic anaemia affects the entire bone marrow. This prospective study was undertaken to develop and standardise a new nuclear medicine technique called 'dynamic bone marrow imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99m Tc S. Colloid, and an index, called the bone marrow uptake index was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. 20 refs.; 4 figs.; 5 tabs

Reactivation of Immunological Response in Lethally X-Irradiated Mice Treated with Isogeneic Bone Marrow

Energy Technology Data Exchange (ETDEWEB)

Stankovic, V.; Slijepcevic, M.; Hrsak, I. [Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

1968-08-15

Male and female C57BL/H and CBA/H mice aged 10-12 weeks were used as recipients and donors, respectively. All recipient mice were given a lethal whole-body X-irradiation dose (850 R for C57BL and 950 R for CBA mice) followed by iv injection of 10 x 106 isogeneic eosin-negative bone-marrow cells suspended in 0.5 ml of Hank's solution. The number of eosin-positive cells was less than 10%. The state of immunological responsiveness of irradiated recipients was measured at different time intervals up to 86 days after irradiation. The immune response to bacterial antigen was measured with the titre of agglutinating antibodies in serum six days after iv antigenic stimulation with a suspension of 2 x 10{sup 7} killed Salmonella typhimurium cells. The immune response to tissue antigens was evaluated by: (a) the effectiveness of the spleen cells from isologous radiation chimeric parental mice in preventing bone marrow from F{sub 1} (C57BL x CBA) hybrid donor from therapeutically affecting lethally irradiated F j recipient mice; (b) the effectiveness of the spleen cells in inducing splenom egaly in recipient F{sub 1} hybrid mice (Simonsen test). It was found that the responsiveness to bacterial antigens reappears much earlier and increases much faster than the immunological responsiveness to tissue antigens. (author)

Community participation in international health: practical recommendations for donor and recipient organizations

Directory of Open Access Journals (Sweden)

Akukwe Chinua

1999-01-01

Full Text Available This article discusses the need for donor agencies and recipient organizations to involve target communities in the conceptualization, development, monitoring, and implementation of health services and programs in international health. This paper assumes that most donor organizations are based in industrialized countries. Given that resources are finite in both developing and developed countries, the article briefly reviews the current trend of declining public funds for health systems and an increasing role for privately funded health services worldwide. The article calls for community-based international health services that reflect the priorities of target populations, and it also discusses practi cal steps to involve local populations in community-based health planning and management in international health.

Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic Web Layer.

Science.gov (United States)

Sernadela, Pedro; González-Castro, Lorena; Carta, Claudio; van der Horst, Eelke; Lopes, Pedro; Kaliyaperumal, Rajaram; Thompson, Mark; Thompson, Rachel; Queralt-Rosinach, Núria; Lopez, Estrella; Wood, Libby; Robertson, Agata; Lamanna, Claudia; Gilling, Mette; Orth, Michael; Merino-Martinez, Roxana; Posada, Manuel; Taruscio, Domenica; Lochmüller, Hanns; Robinson, Peter; Roos, Marco; Oliveira, José Luís

2017-01-01

Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries.

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

Directory of Open Access Journals (Sweden)

Pedro Xavier-Elsas

2015-01-01

Full Text Available Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp- deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

Stem and stromal cell reconstitution of lethally irradiated mice following transplantation of hematopoietic tissue from donors of various ages

International Nuclear Information System (INIS)

Schmidt, C.M.; Doran, G.A.; Crouse, D.A.; Sharp, J.G.

1987-01-01

If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothesis, we used 12- and 8-day spleen colony formation (CFU-s) to assay more and less primitive stem cell subpopulations of three murine hematopoietic tissues: fetal liver (FL) and weanling (WBM) and adult (ABM) bone marrow. Subsequently, the same assays and a stromal cell assay were performed on the bone marrow from groups of lethally irradiated mice reconstituted with these tissues. Comparison of the CFU-s content of the donor tissues revealed that FL contained a significantly greater proportion of primitive stem cells as evidenced by a (Day 12):(Day 8) CFU-s ratio of 3.0 +/- 1.0 as compared to 0.9 +/- 0.1 for WBM and ABM. In addition, at 21 weeks post-transplantation the CFU-s/femur values of the FL reconstituted group were significantly greater than those of the ABM and WBM reconstituted groups. These results suggest that fetal hematopoietic tissue contains a greater proportion of primitive stem cells and has a greater proliferative potential than hematopoietic tissue from older donors. No differences were seen in stromal cell reconstitution of the three experimental groups. In all cases, assayable fibroblast colony forming cells (CFU-f) remained at 20-40% of control values, even at 21 weeks postreconstitution

Characterization of Fatty Acid Composition in Bone Marrow Fluid From Postmenopausal Women: Modification After Hip Fracture.

Science.gov (United States)

Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J; Seitz, Germán; Rodríguez, J Pablo

2016-10-01

Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65-80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. J. Cell. Biochem. 117: 2370-2376, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice

International Nuclear Information System (INIS)

Perkins, S.; Fleischman, R.A.

1988-01-01

Studies of bone marrow transplant patients have suggested that the stromal cells of the in vitro hematopoietic microenvironment are transplantable into conditioned recipients. Moreover, in patients with myeloproliferative disorders, all of the stromal cells, which include presumptive endothelial cells, appear to be derived from hematopoietic precursors. To confirm these findings, we have constructed two chimeric mouse models: (a) traditional radiation chimeras, and (b) fetal chimeras, produced by placental injection of bone marrow into genetically anemic Wx/Wv fetuses, a technique that essentially precludes engraftment of nonhematopoietic cells. Using two-color indirect immunofluorescence, the stromal cells in long-term bone marrow culture derived from these chimeras were analyzed for donor or host origin by strain-specific H-2 antigens, and for cell lineage by a variety of other specific markers. 75-95% of the stromal cells were shown to be hematopoietic cells of the monocyte-macrophage lineage, based upon donor origin, phagocytosis, and expression of specific hematopoietic surface antigens. The remaining 5-25% of the stromal cells were exclusively host in origin. Apart from occasional fat cells, these cells uniformly expressed collagen type IV, laminin, and a surface antigen associated with endothelial cells. Since these endothelial-like cells are not transplantable into radiation or fetal chimeras, they are not derived from hematopoietic stem cells. The contrast between our findings and human studies suggests either unexpected species differences in the origin of stromal lineages or limitations in the previous methodology used to detect nonhematopoietic stromal cells

Peer-to-peer milk donors' and recipients' experiences and perceptions of donor milk banks.

Science.gov (United States)

Gribble, Karleen D

2013-07-01

To explore the intersection of peer-to-peer milk sharing and donor milk banks. A descriptive survey design containing closed and open-ended questions was used to examine women's perceptions of peer-to-peer milk sharing and milk banking. Closed-ended questions were analyzed using descriptive statistics and conventional qualitative content analysis was used to analyze open-ended responses. Participants were recruited via the Facebook sites of two online milk-sharing networks (Human Milk 4 Human Babies and Eats on Feet). Ninety-eight milk donors and 41 milk recipients who had donated or received breast milk in an arrangement that was facilitated via the Internet. One half of donor recipients could not donate to a milk bank because there were no banks local to them or they did not qualify as donors. Other respondents did not donate to a milk bank because they viewed the process as difficult, had philosophical objections to milk banking, or had a philosophical attraction to peer sharing. Most donor respondents felt it was important to know the circumstances of their milk recipients. No recipient respondents had obtained milk from a milk bank; it was recognized that they would not qualify for banked milk or that banked milk was cost prohibitive. Peer-to-peer milk donors and recipients may differ from milk bank donors and recipients in significant ways. Cooperation between milk banks and peer sharing networks could benefit both groups. © 2013 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

International Nuclear Information System (INIS)

Azuma, E.; Yamamoto, H.; Kaplan, J.

1989-01-01

Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients

Breast milk donation: women's donor experience.

Science.gov (United States)

Alencar, Lucienne Christine Estevez de; Seidl, Eliane Maria Fleury

2009-02-01

To describe the characteristics of donation behavior and identify reasons, beliefs and feelings relative to this practice, based on the reports of donor women. Personal and social-environmental aspects, which seem to affect donation behavior in donors and former donors, were also investigated. An exploratory, descriptive and cross-sectional study was carried out with women donors at two breast-milk banks within the public health system of the Brazilian Federal District. Data was collected from July to September 2005. The participants were 36 women, aged 14 to 33 years (average=24.78; SD=5.22), with different levels of schooling, 58.3% of which were first-time mothers. Data gathering was based on interviews carried out during home visits. In addition to descriptive statistical analyses of quantitative data, a qualitative data categorical analysis was also performed. The most frequently reported reasons for donating breast milk were altruism and excess milk production. The most frequent time interval for donation was 13 days after delivery. Contact by phone with the milk bank was the most common means of communication used by the majority of participants (n=22) to obtain information that enabled the donating process. Psychosocial aspects identified and the experience of donors can contribute to the empowerment of the formal and informal social donation-support network, in addition to serving as a driver for the implementation of technical and policy strategies in promoting future donation practices.

The side-effects of the "Facebook effect": challenging Facebook's "organ donor" application.

Science.gov (United States)

Peña, Adam M

2014-01-01

A recent study published in the American Journal of Organ Transplantation proposes that an organ donor application in Facebook can increase the rates at which individuals donate organs. While I offer support for the use of social media mechanisms in the service of the promotion of organ donation public health initiatives, there are several ethical concerns surrounding informed consent. While Facebook has made a noble effort to aid public health initiatives focused on organ donation, the current application does not promote decisions that are based on individuals' personal values and goals. Without an intervention that promotes an understanding and appreciation of a decision for or against donation, the application does not obtain informed consent. Without first ensuring that a Facebook member has registered with her or his own state donor registry, this social media mechanism may create more confusion than clarity about an individual's organ donor status. If Facebook desires to have a positive impact on the rates of organ donation, it must do so in a manner that obtains proper consent and promotes ethically informed decisions.

The Willed Body Donor Interview Project: Medical Student and Donor Expectations

Science.gov (United States)

Bohl, Michael; Holman, Alexis; Mueller, Dean A.; Gruppen, Larry D.; Hildebrandt, Sabine

2013-01-01

The Anatomical Donations Program at the University of Michigan Medical School (UMMS) has begun a multiphase project wherein interviews of donors will be recorded and later shown to medical students who participate in the anatomical dissection course. The first phase of this project included surveys of both current UMMS medical students and donors…

[Registries for rare diseases : OSSE - An open-source framework for technical implementation].

Science.gov (United States)

Storf, Holger; Schaaf, Jannik; Kadioglu, Dennis; Göbel, Jens; Wagner, Thomas O F; Ückert, Frank

2017-05-01

Meager amounts of data stored locally, a small number of experts, and a broad spectrum of technological solutions incompatible with each other characterize the landscape of registries for rare diseases in Germany. Hence, the free software Open Source Registry for Rare Diseases (OSSE) was created to unify and streamline the process of establishing specific rare disease patient registries. The data to be collected is specified based on metadata descriptions within the registry framework's so-called metadata repository (MDR), which was developed according to the ISO/IEC 11179 standard. The use of a central MDR allows for sharing the same data elements across any number of registries, thus providing a technical prerequisite for making data comparable and mergeable between registries and promoting interoperability.With OSSE, the foundation is laid to operate linked patient registries while respecting strong data protection regulations. Using the federated search feature, data for clinical studies can be identified across registries. Data integrity, however, remains intact since no actual data leaves the premises without the owner's consent. Additionally, registry solutions other than OSSE can participate via the OSSE bridgehead, which acts as a translator between OSSE registry networks and non-OSSE registries. The pseudonymization service Mainzelliste adds further data protection.Currently, more than 10 installations are under construction in clinical environments (including university hospitals in Frankfurt, Hamburg, Freiburg and Münster). The feedback given by the users will influence further development of OSSE. As an example, the installation process of the registry for undiagnosed patients at University Hospital Frankfurt is described in more detail.

Breast milk donors in France: a portrait of the typical donor and the utility of milk banking in the French breastfeeding context.

Science.gov (United States)

Azema, Emilie; Callahan, Stacey

2003-05-01

Although information regarding attitudes and characteristics of human blood donors has been researched, little is known about the motivations and demographic and personality characteristics of women who choose to donate their breast milk. Eight milk banks in France participated in a study examining donor characteristics, providing data on 103 women. The results showed that the donors were women of average childbearing age with strong support at home. Almost half did not work outside of the home, compared to the national average of 80% of women in this age group; similarly, a large number (currently working or not) were from the health and social services fields. Reasons for donation were largely altruistic, and a general optimistic attitude prevailed within the participants. The results of this study provide useful information for the recruitment of potential donors as well as information on how to facilitate and provide optimal service through milk donation.

Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus

International Nuclear Information System (INIS)

Matsumoto, K.; Yoshikai, Y.; Asano, T.; Himeno, K.; Iwasaki, A.; Nomoto, K.

1991-01-01

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr----AKR and C3H/lpr----AKR chimeras, CD4 single-positive thymocytes contained an increased number of V beta 6+ cells in spite of potentially deleting alleles of Mlsa, whereas V beta 6+ mature T cells were deleted in the MRL/+ ----AKR and C3H/+ ----AKR chimeras. There was no difference between MRL/+ ----AKR and MRL/lpr----AKR chimeras in their proportion of V beta 3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr----AKR chimeras, in particular in the forbidden V beta 6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus

Why search for a sperm donor online? The experiences of women searching for and contacting sperm donors on the internet.

Science.gov (United States)

Jadva, Vasanti; Freeman, Tabitha; Tranfield, Erika; Golombok, Susan

2018-06-01

Whilst studies have examined the experiences of women who use clinic donors, to date there has been limited research investigating women's motivations and experiences of searching for a sperm donor online. A total of 429 women looking for a sperm donor on Pride Angel (a website that facilitates contact between donors and recipients) completed an online survey. Fifty-eight percent (249) saw advantages of obtaining donated sperm online with the most common advantage reported as being able to connect with and meet the donor (n = 50 (24%)). A third (n = 157 (37%)) of the participants gave disadvantages, the most common reported was encountering 'dishonest donors' (n = 63 (40%)). Most recipients (n = 181 (61%)) wanted the donor to be 'just a donor' (i.e. to provide sperm and have no further contact). Whilst it was important for recipients to know the identity of the donor, some did not see this as important for the child and thus the level of information that parents have about the donor, and that which the child has, can differ. Finding a donor online blurs the distinction between categories of 'anonymous', 'known' and 'identity release' donations. Whilst the survey had a large sample size, the representativeness of the sample is not known.

Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

International Nuclear Information System (INIS)

Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

1997-01-01

Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

Organ donors: deceased or alive? Quo vadis?

Science.gov (United States)

Rozental, R

2006-01-01

Irrespectively of universal shortage of donor organs there is a tendency of increasing the number of transplantations from living and deceased donors. Each of these two methods has positive and negative features. The main obstacles using living donors are health hazard, necessity to solve certain donor's social and psychological problems, possibility of organ trade and moving. The main problems connected with organ retrieval from deceased donors are possible conflicts with public opinion: difficulties in interpretation of brain death, legislation, obtaining of informed consent from donor's relatives, etc. Future progress in organ transplantation may take place through activation of organ retrieval from deceased donors. The most perspective ways are change to presumed consent in all countries, establishing of centralized system of donor detection and registration, intensification of transplant coordination, active contacts with mass-media, etc. It is necessary to increase (enhance) participation of the members of the public in organ donation process, to develop solidarity among the public members and to involve public authorities to deal with this problem. Bioethical standards should be put in accordance with common progress and some ethical traditions should be changed.

78 FR 54956 - Agency Information Collection (Open Burn Pit Registry Airborne Hazard Self-Assessment...

Science.gov (United States)

2013-09-06

...: Open Burn Pit Registry Airborne Hazard Self-Assessment Questionnaire, VA Form 10-10066. Type of Review... services to Open Burn Pit Registry participants and improve VA's ability to understand the health effects... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-NEW] Agency Information Collection (Open Burn...

Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

International Nuclear Information System (INIS)

Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

1981-01-01

Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed

Development of an International Prostate Cancer Outcomes Registry.

Science.gov (United States)

Evans, Sue M; Nag, Nupur; Roder, David; Brooks, Andrew; Millar, Jeremy L; Moretti, Kim L; Pryor, David; Skala, Marketa; McNeil, John J

2016-04-01

To establish a Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ) for monitoring outcomes of prostate cancer treatment and care, in a cost-effective manner. Stakeholders were recruited based on their interest, importance in achieving the monitoring and reporting of clinical practice and patient outcomes, and in amalgamation of existing registries. Each participating jurisdiction is responsible for local governance, site recruitment, data collection, and data transfer into the PCOR-ANZ. To establish each local registry, hospitals and clinicians within a jurisdiction were approached to voluntarily contribute to the registry following relevant ethical approval. Patient contact occurs following notification of prostate cancer through a hospital or pathology report, or from a cancer registry. Patient registration is based on an opt-out model. The PCOR-ANZ is a secure web-based registry adhering to ISO 27001 standards. Based on a standardised minimum data set, information on demographics, diagnosis, treatment, outcomes, and patient reported quality of life, are collected. Eight of nine jurisdictions have agreed to contribute to the PCOR-ANZ. Each jurisdiction has commenced implementation of necessary infrastructure to support rapid rollout. PCOR-ANZ has defined a minimum data set for collection, to enable analysis of key quality indicators that will aid in assessing clinical practice and patient focused outcomes. PCOR-ANZ will provide a useful resource of risk-adjusted evidence-based data to clinicians, hospitals, and decision makers on prostate cancer clinical practice. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

Science.gov (United States)

Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

2017-09-01

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p donor risk index and center volume was not statistically significant (p = 0.747), confirming that the risk associated with using marginal donor livers was comparable between smaller and larger centers. Results were consistent when examining graft loss. At both small and large centers, high-risk donor allografts were associated with reduced patient and graft survival after liver transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

Summary of data held by the National Registry for Radiation Workers

CERN Document Server

Saw, G M A

1985-01-01

This supplement to NRPB-R116 (Protocol for the National Registry for Radiation Workers) summarises the data held by the National Registry for Radiation Workers) at the end of 1983. It follows the form of the first supplement which described the data base at the end of 1981. The total population for which agreement has been reached with the participating organisations is about 68,000. Over 86% of these have ben registered, arrangements are in hand to include most of the remainder. Only 2% of the population have refused to participate as individuals. Although some information is still outstanding, there has been a considerable improvement since 1981. More details are given for each of the participating organisations. Further supplements will be issued from time to time as more data are received.

Hyper IgM Syndrome: a Report from the USIDNET Registry.

Science.gov (United States)

Leven, Emily A; Maffucci, Patrick; Ochs, Hans D; Scholl, Paul R; Buckley, Rebecca H; Fuleihan, Ramsay L; Geha, Raif S; Cunningham, Coleen K; Bonilla, Francisco A; Conley, Mary Ellen; Ferdman, Ronald M; Hernandez-Trujillo, Vivian; Puck, Jennifer M; Sullivan, Kathleen; Secord, Elizabeth A; Ramesh, Manish; Cunningham-Rundles, Charlotte

2016-07-01

The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM). The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality. Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients' age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years). Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

Clinical Case Registries (CCR)

Data.gov (United States)

Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

[Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient].

Science.gov (United States)

Jindra, P; Žejšková, L; Peková, S; Navrátilová, J; Schutzová, M; Vokurka, S; Koza, V

2012-01-01

Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

Directory of Open Access Journals (Sweden)

Tatsuya Ito

Full Text Available Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs. In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs.The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries.Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data.New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants.There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

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Poiré, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J; Volin, Liisa; Russell, Nigel H; Socié, Gérard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon

2018-02-01

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 ( FLT3 -ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3 -ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively ( P <0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft- versus -host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3 -ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients. Copyright© 2018 Ferrata Storti Foundation.

Scar evaluation of split thickness skin graft donor site

Directory of Open Access Journals (Sweden)

Jani Muha

2014-12-01

Full Text Available BACKGROUND. Split thickness skin graft harvesting causes a certain degree of scaring on the donor site. Donor site scar can cause aesthetic and functional sequelae on the patient's body. Our goal was to study the process of donor site selection, and then evaluate donor site scars and their impact on patients. PATIENTS AND METHODS. This retrospective study included 45 patients aged 5 to 61 years (in average 36, who have been treated with STSG in the 2004–2010 period. 57.8% of them were men. On a follow-up visit, we photographed healed skin defects and donor sites. We then determined and compared the surface areas of skin defect and the donor site using the Adobe® Illustrator® CS5 computer program. Donor site scars were assessed according to the Vancouver scar scale (VSS. We examined scar’s light touch sensitivity with monofilaments and skin colouring compared to adjacent healthy skin using colorimeter. Patients were also interviewed about their treatment course in a form of a standardized questionnaire. RESULTS. Our research has revealed that 20.0% of patients participated in the decision making process of choosing the donor site, while in 80.0% the donor site was chosen by the surgeon himself. 6.7% of patients were not satisfied with their donor site. Most of the patients (37/45 had donor sites on their thighs. In average, the donor site surface area was 94% bigger than the skin defect area. We found statistically significant differences in VSS values, light touch sensitivity and skin colouring between donor site scaring and adjacent healthy skin. CONCLUSIONS. Donor site scar can represent a lasting aesthetic and functional disability for patients. Our research has shown that most of the patients do not participate in the donor site selection process, but are satisfied with their donor site. In most cases, STGSs are harvested from the thigh, other anatomical regions, where scarring would be aesthetically less obtrusive, are underused

Determination of an unrelated donor pool size for human leukocyte antigen-matched platelets in Brazil

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Carolina Bonet Bub

2016-02-01

Full Text Available ABSTRACT Background: Successful transfusion of platelet refractory patients is a challenge. Many potential donors are needed to sustain human leukocyte antigen matched-platelet transfusion programs because of the different types of antigens and the constant needs of these patients. For a highly mixed population such as the Brazilian population, the pool size required to provide adequate platelet support is unknown. Methods: A mathematical model was created to estimate the appropriate size of an unrelated donor pool to provide human leukocyte antigen-compatible platelet support for a Brazilian population. A group of 154 hematologic human leukocyte antigen-typed patients was used as the potential patient population and a database of 65,500 human leukocyte antigen-typed bone marrow registered donors was used as the donor population. Platelet compatibility was based on the grading system of Duquesnoy. Results: Using the mathematical model, a pool containing 31,940, 1710 and 321 donors would be necessary to match more than 80% of the patients with at least five completely compatible (no cross-reactive group, partial compatible (one cross-reactive group or less compatible (two cross-reactive group donors, respectively. Conclusion: The phenotypic diversity of the Brazilian population has probably made it more difficulty to find completely compatible donors. However, this heterogeneity seems to have facilitated finding donors when cross-reactive groups are accepted as proposed by the grading system of Duquesnoy. The results of this study may help to establish unrelated human leukocyte antigen-compatible platelet transfusions, a procedure not routinely performed in most Brazilian transfusion services.

Immune reconstitution in patients with Fanconi anemia after allogeneic bone marrow transplantation.

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Perlingeiro Beltrame, Miriam; Malvezzi, Mariester; Bonfim, Carmem; Covas, Dimas Tadeu; Orfao, Alberto; Pasquini, Ricardo

2014-07-01

Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions, including hematopoietic stem cell transplantation (HSCT). Successful BM transplantation (BMT) requires reconstitution of normal immunity. In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and natural killer (NK) lymphocytes in 23 patients with Fanconi anemia before and after BMT on days +30, +60, +100, +180, +270 and +360. In parallel, we evaluated the effect of related versus unrelated donor marrow as well as the presence of graft-versus-host disease (GVHD). After transplantation, we found different kinetics of recovery for the distinct major subsets of lymphocytes. NK cells were the first to recover, followed by cytotoxic CD8(+) T cells and B cells, and finally CD4(+) helper T cells. Early lymphocyte recovery was at the expense of memory cells, potentially derived from the graft, whereas recent thymic emigrant (CD31(+) CD45RA(+)) and naive CD4(+) or CD8(+) T cells rose only at 6 months after HSCT, in the presence of immunosuppressive GVHD prophylactic agents. Only slight differences were observed in the early recovery of cytotoxic CD8(+) T cells among those cases receiving a graft from a related donor versus an unrelated donor. Patients with GVHD displayed a markedly delayed recovery of NK cells and B cells as well as of regulatory T cells and both early thymic emigrant and total CD4(+) T cells. Our results support the utility of post-transplant monitoring of a peripheral blood lymphocyte subset for improved follow-up of patients with Fanconi anemia undergoing BMT. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

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Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report 2017—Pancreas Waiting List, Recipients, and Donors

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Webster, Angela C; Hedley, James; Patekar, Abhijit; Robertson, Paul; Kelly, Patrick J

2017-01-01

Abstract This is a registry report from the Australia and New Zealand Islet and Pancreas Transplant Registry. We report data for all solid organ pancreas transplant activity from inception in 1984 to end of 2016. Data analysis was performed using Stata Software version 14 (StataCorp, College Station, Tex). From 1984 to 2016 a total of 756 solid organ pancreas transplants have been performed in Australia and New Zealand, in 738 individuals. In 2016, 55 people received a pancreas transplant. These transplants were performed in Auckland (4), Monash (22), and Westmead (29). In 2016, 50 transplants were simultaneous pancreas kidney, 4 were pancreas after kidney, and 1 was a pancreas transplant alone. PMID:29026874

Study on proliferative responses to host Ia antigens in allogeneic bone marrow chimera in mice: sequential analysis of the reactivity and characterization of the cells involved in the responses

International Nuclear Information System (INIS)

Iwabuchi, K.; Ogasawara, K.; Ogasawara, M.; Yasumizu, R.; Noguchi, M.; Geng, L.; Fujita, M.; Good, R.A.; Onoe, K.

1987-01-01

Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells to permit serial analysis of the developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host, or third party antigens. We found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens were generated by the thymocytes obtained from the irradiation chimeras at an early stage after bone marrow reconstitution. The majority of the responding thymocytes had surfaces lacking demonstrable peanut agglutinin receptors and were donor type Thy-1+, Ly-2-, and L3T4+ in both anti-recipient and anti-third party MLR. In anti-host responses, however, Ly-2+ thymocytes seemed to be at least partially involved. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter, whereas the capacity to mount MLR against third party antigens persisted. The spleen cells of [B10----AKR] chimeras at the same time developed a more durable capability to exhibit anti-host reactivities and a permanent capability of reacting to third party allo-antigens. The stimulator antigens were Ia molecules on the stimulator cells in both anti-recipient and anti-third party MLR. The responding splenocytes were of donor origin and most of them had Thy-1+, Ly-1+2-, and L3T4+ phenotype

Primary healthcare-based diabetes registry in Puducherry: Design and methods

Directory of Open Access Journals (Sweden)

Subitha Lakshminarayanan

2017-01-01

Full Text Available Background: Diabetes registries monitor the population prevalence and incidence of diabetes, monitor diabetes control program, provide information of quality of care to health service providers, and provide a sampling frame for interventional studies. This study documents the process of establishing a prospective diabetes registry in a primary health-care setting in Puducherry. Methods: This is a facility-based prospective registry conducted in six randomly selected urban health centers in Puducherry, with enrollment of all known patients with diabetes attending chronic disease clinics. Administrative approvals were obtained from Government Health Services. Manuals for training of medical officers, health-care workers, and case report forms were developed. Diabetes registry was prepared using Epi Info software. Results: In the first phase, demographic characteristics, risk factors, complications, coexisting chronic conditions, lifestyle and medical management, and clinical outcomes were recorded. Around 2177 patients with diabetes have been registered in six Primary Health Centres out of a total of 2948 participants seeking care from chronic disease clinic. Registration coverage ranges from 61% to 105% in these centers. Conclusion: This study has documented methodological details, and learning experiences gained while developing a diabetes registry at the primary health care level and the scope for upscaling to a Management Information System for Diabetes and a State-wide Registry. Improvement in patient care through needs assessment and quality assurance in service delivery is an important theme envisioned by this registry.