Abstract:
:Introduction of genes conferring drug resistance into hematopoietic cells may allow for improved chemotherapy by protection of normally drug-sensitive cells from the toxic side-effects of antitumor agents. We recently reported that transplantation of murine marrow transgenic for drug-resistant dihydrofolate reductase (DHFR) protected mice from lethal doses of methotrexate (MTX), demonstrating the feasibility of imparting drug resistance to recipients of marrow expressing drug-resistant DHFR activity. In order to optimize this strategy it is necessary to identify the hematopoietic cell populations which mediate drug resistance. For this purpose, we separated committed progenitor populations from primitive hematopoietic cells in DHFR transgenic marrow by counterflow elutriation (CE). As expected, supplementation with a fraction containing committed progenitors afforded protection from MTX-induced aplasia observed early after transplantion in animals administered MTX. In contrast, supplementation with a fraction containing primitive hematopoietic cells depleted of committed progenitors failed to provide immediate protection from early aplasia, but instead contributed to drug resistance 4 to 5 weeks after transplantation. The presence of primitive hematopoietic progenitors in both fractions was evident from Southern hybridization analysis for donor transgenic cells 2 months post-transplant. We conclude that protection from aplasia associated with MTX administration immediately after transplantation requires expression of drug-resistant DHFR activity in more differentiated, committed hematopoietic cells, while primitive DHFR transgenic progenitors contribute to long-term drug resistance. These results help to define the appropriate target cells for improved chemotherapy by protection of hematopoietic cells through the introduction of new genes conferring drug resistance.
journal_name
Bone Marrow Transplantjournal_title
Bone marrow transplantationauthors
James R,May C,Diers M,Wagner J,McIvor Rdoi
10.1038/sj.bmt.1701984subject
Has Abstractpub_date
1999-10-01 00:00:00pages
815-21issue
8eissn
0268-3369issn
1476-5365journal_volume
24pub_type
杂志文章abstract::The use of mobilized peripheral blood (PB) stem cells for autologous transplantation initially generated much enthusiasm because of enhanced engraftment in comparison to marrow stem cells and avoidance of general anesthesia for the donor. Its application to the allogeneic setting seemed inevitable. For obvious ethical...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/sj.bmt.1702464
更新日期:2000-07-01 00:00:00
abstract::Considerable evidence in preclinical models as well as in human transplantation now suggests that donor-derived natural killer (NK) cells can contribute to alloimmune recognition of recipient residual tumour cells. This makes the NK cell population an attractive target for in vitro or in vivo manipulations, in order t...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704711
更新日期:2005-01-01 00:00:00
abstract::Six hundred and fifteen centers from 45 countries reported a total 30,293 HSCT to this 2008 EBMT survey with 26,810 first transplants (40% allogeneic, 60% autologous). This corresponds to an increase of 7% for the allogeneic and 3% for the autologous HSCT. Main indications were leukemias (32%; 89% allogeneic); lymphom...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/bmt.2010.69
更新日期:2011-02-01 00:00:00
abstract::Alefacept (Amevive) is an immunosuppressive dimeric fusion protein that is used for psoriasis control. We recently showed its effect in acute steroid-resistant/dependent GVHD. In this study, we describe the effect of alefacept treatment on chronic extensive GVHD (cGVHD). Twelve patients were included in this study; of...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/bmt.2008.324
更新日期:2009-02-01 00:00:00
abstract::We examined the effects of bone marrow transplantation (BMT) on immune-mediated inner ear diseases in MRL/Mp-lpr/lpr (MRL/lpr) mice, which manifest not only lupus nephritis but also sensorineural hearing loss (SNHL) at the age of 20 weeks. These mice were treated with cyclophosphamide (CY) and irradiation (5 Gy x 2), ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1702636
更新日期:2000-10-01 00:00:00
abstract::Recent studies from this laboratory have shown that unmanipulated, MHC-mismatched allogeneic bone marrow (BM) engrafts and produces complete allogeneic chimerism when administered to recipient mice 8 days following lethal irradiation and reconstitution with T cell-depleted (TCD) syngeneic bone marrow. Host lymphopoiet...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/bmt.2014.62
更新日期:2014-08-01 00:00:00
abstract::Progression of Philadelphia-negative myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) to acute myeloid leukemia (AML) is an adverse event in the course of the disease. Although allogeneic hematopoietic SCT (allo-SCT) is considered as the only curative therapy, few data exist on the ou...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,多中心研究
doi:10.1038/bmt.2014.31
更新日期:2014-06-01 00:00:00
abstract::On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/s41409-019-0451-2
更新日期:2019-11-01 00:00:00
abstract::Cyclosporine A (CsA) therapy based on 2-h concentrations (C2) after oral administration has demonstrated low acute rejection rates after solid organ transplantation. We analysed the correlation between C2 and trough (C0) levels of oral CsA therapy in samples obtained twice in consecutive weeks from 58 patients during ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1705788
更新日期:2007-10-01 00:00:00
abstract::Depletion of donor CD6+ cells in HLA-identical allogeneic bone marrow transplantation has been reported to reduce graft-versus-host disease without interfering with engraftment. We have established an immunomagnetic cell separation technique capable of producing a 2-3 log depletion of CD6+ cells. Median recovery of CD...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Bone marrow (BM) histiocystosis in association with the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) is a rare phenomenon with few published cases. We report two cases of BM histiocystosis in patients with Hodgkin's disease treated with GM-CSF after autologous bone marrow transplantation...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/sj.bmt.1701036
更新日期:1998-01-01 00:00:00
abstract::The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine prod...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704302
更新日期:2004-01-01 00:00:00
abstract::Fentanyl is a synthetic opioid that can be delivered through a transdermal therapeutic system (TTS). The aim of this study was to assess the efficacy of fentanyl TTS in treating oral mucositis pain in 75 adult hematopoietic stem cell transplant (HSCT) patients. The analysis was based on 62 patients who developed mucos...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bmt.1704515
更新日期:2004-06-01 00:00:00
abstract::Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Childhood histiocytoses comprise two main diseases, Langerhans cell histiocytosis (LCH) and hemophagocytic lymphohistiocytosis (HLH). LCH is a rare disorder with obscure pathogenesis. Data on clonality suggested neoplastic origin, yet were not convincing. Dysregulation of cytokines and of DC trafficking and cross-talk...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/bmt.2008.46
更新日期:2008-06-01 00:00:00
abstract::Omenn syndrome is a variant of SCID, inherited as an autosomal recessive disorder, and characterized by severe eczematoid dermatitis, eosinophilia, elevated serum IgE and a distinctive histology in enlarged lymph nodes. The etiology of Omenn syndrome is unknown, however, unlike other forms of SCID; patients with Omenn...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::In the 1980s it became clear that low numbers of primitive hematopoietic cells were present in the peripheral bloodstream. Early clinical trials by investigators in the USA, Australia, and Germany demonstrated that these cells could be collected and reinfused to support high-dose chemotherapy procedures in patients ot...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/sj.bmt.1701667
更新日期:1999-05-01 00:00:00
abstract::Peg-filgrastim is a form of G-CSF with a sustained duration of action due to self-limited clearance. We administered 6 mg peg-filgrastim to 18 autograft recipients on day +1 after transplantation for hematologic malignancies. Plasma samples were collected at baseline and during transplantation. Hematopoietic recovery ...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bmt.1705772
更新日期:2007-09-01 00:00:00
abstract::Allogeneic hematopoietic SCT (HSCT) is currently the only curative treatment for myelodysplastic syndrome (MDS). However, many patients cannot find an HLA-matched donor. We have developed a new protocol for HLA-mismatched (including haploidentical) HSCT using G-CSF-primed BM plus G-CSF-mobilized PBSCs without in vitro...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/bmt.2009.351
更新日期:2010-08-01 00:00:00
abstract::The era of reduced-intensity allogeneic stem cell transplantation, with its emphasis on older patients, has created new challenges in the management of what is now an older related stem cell donor population. These donors are now on average no less than 10 years older than in the mid-1990s. Donors over 70 years of age...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/bmt.2016.201
更新日期:2017-01-01 00:00:00
abstract::Up to 10% of germ cell tumor patients require salvage high-dose chemotherapy with stem cell support, achieving cure rates in the range of 10-60%. Stem cell mobilization may be difficult in these patients because of multiple lines of treatment known to seriously hamper stem cell recovery. Plerixafor significantly enhan...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/bmt.2010.264
更新日期:2011-08-01 00:00:00
abstract::We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophi...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Post-transplant lymphoproliferative disorders (PTLD) are morphologically/clinically heterogeneous. The main goal of this study was to define the histogenesis of PTLD (B-cell phenotype, EBV-related) in seven pediatric patients after allogeneic T-cell-depleted bone marrow transplantation. Immunohistochemical stains usin...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704395
更新日期:2004-02-01 00:00:00
abstract::Thrombotic microangiopathy is one of the complications of bone marrow transplantation and is related to other complications such as graft-versus-host disease, veno-occlusive disease, diffuse alveolar hemorrhage, and cytomegalovirus infection. Thrombotic microangiopathy occurred in three out of 12 patients who underwen...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1701890
更新日期:1999-08-01 00:00:00
abstract::This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a medi...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/sj.bmt.1704759
更新日期:2005-02-01 00:00:00
abstract::We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1700743
更新日期:1997-04-01 00:00:00
abstract::Recent reports have suggested that the total number of autologous or allogeneic hematopoietic stem cell (HSC) infused after high-dose chemotherapy might predict survival, post-transplant morbidity and rate of hematopoietic engraftment. However, HSC capable of long-term multilineage potential are still poorly defined, ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::To evaluate a strategy of one cycle of dose-intensive chemotherapy for patients with Hodgkin's disease in sensitive relapse and two cycles for those with refractory disease, 122 patients received dose-intensive chemotherapy followed by autotransplant in two consecutive studies. Patients with refractory disease were of...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bmt.1700682
更新日期:1997-03-01 00:00:00
abstract::The purpose of this study was two-fold: to describe the quality of life and behavioral adjustment of survivors of pediatric bone marrow transplantation (BMT) prior to and 6 months post-BMT; and, to identify correlates of survivors' quality of life and behavioral adjustment. Participants were 26 children and adolescent...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1702527
更新日期:2000-08-01 00:00:00