Abstract:
:Graft rejection and graft-versus-host disease are major problems in mismatched marrow transplants along with toxicity from standard myeloablative host treatments. We have established a tolerization model, using 1 Gy irradiation, which reduces stem cell capacity to < 10% of control while causing minimal myelosuppression, donor antigen pre-exposure (spleen cells), CD40-ligand antibody blockade and high levels of marrow (40 x 106 cells), which allows for stable long-term multilineage engraftment in H2-mismatched murine marrow transplants. We now show that the establishment of 'microchimaerism' (0.5-3.8%) sets the stage for macrochimaerism, with subsequent marrow infusions in H2-mismatched mice with CD40-ligand blockade only. Neither irradiation nor spleen cell exposure were necessary. When 40 x 106 bone marrow cells were infused on weeks 0, 12, 14 and 16, blood engraftment was about seven times the single 40 x 106 control. When marrow cells were given on weeks 0, 3, 4, 5 and 6, engraftment at 24 weeks post transplant was 17.9 +/- 1.2%, compared with 2.7 +/- 0.8% for the single 40 x 106 control (P = 0.009). We have shown stable, long-term multilineage chimaerism and established that the schedule of marrow administration, not the total cell dose, is critical for tolerization. This approach indicates that microchimaerism can tolerize for subsequent marrow infusions and produce macrochimaerism. This strategy could be applied in clinical human transplants.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Lambert JF,Colvin GA,Zhong S,Wang H,D'Hondt L,Abedi M,Frimberger AE,Stewart FM,Quesenberry PJdoi
10.1046/j.1365-2141.2002.03801.xsubject
Has Abstractpub_date
2002-10-01 00:00:00pages
155-63issue
1eissn
0007-1048issn
1365-2141pii
3801journal_volume
119pub_type
杂志文章abstract::Although 5-fluorouracil (FUra) has been the drug of choice for the treatment of patients with advanced colorectal carcinoma, the response rates are in the range of 15% and the median survival times do not exceed 9 months. Interferon alpha (IFN alpha) has limited antitumour activity in this disease. Recent clinical tri...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08120.x
更新日期:1991-10-01 00:00:00
abstract::Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple my...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06052.x
更新日期:2006-06-01 00:00:00
abstract::Polycythaemia vera (PV) patients have an overall comparatively favourable prognosis, but disease progression is very heterogeneous and life-threatening thrombosis and bleedings are frequent complications in untreated disease. Moreover, transformation to more severe secondary myelofibrosis and acute myeloid leukaemia c...
journal_title:British journal of haematology
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doi:10.1111/bjh.16450
更新日期:2020-06-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is an incurable mature B cell proliferation, combining the unfavourable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL has an even worse prognosis and new treatment options are clearly needed. We analysed the effects of BL22, an immunotoxin composed of the...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07939.x
更新日期:2010-01-01 00:00:00
abstract::This phase 2 study (N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72 mg/m(2) d 1, 8, 15; B: 72 mg/m(2) ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.13214
更新日期:2015-03-01 00:00:00
abstract::Sixty years ago there was little interest in venous thromboembolism (VTE) in global medical circles, and the British were no different in this respect. And yet, from nowhere the clinical field has developed: now prevention and management of VTE accounts for a large part of many consultant haematologists' working life,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17152
更新日期:2020-11-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01973.x
更新日期:2000-04-01 00:00:00
abstract::Monoclonal B-cell populations have been detected in the peripheral blood of apparently healthy individuals by flow cytometry. In 2005, the term monoclonal B-cell lymphocytosis (MBL) was proposed to describe these findings. MBL may be immunophenotypically similar to chronic lymphocytic leukaemia (CLL) and, like CLL, th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06870.x
更新日期:2007-12-01 00:00:00
abstract::We have previously shown that polymorphonuclear leucocytes (PMN) harvested from children with cancer and exposed to chemotherapy exhibit defective bactericidal activities against both Gram-positive and Gram-negative microorganisms as well as accelerated apoptosis. In this study, PMN from children with cancer were eval...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01589.x
更新日期:1999-09-01 00:00:00
abstract::Although the beta thalassaemia trait affects millions of people worldwide, there have been no controlled studies to determine whether it is associated with any clinical disability or abnormal physical signs. To address this question, 402 individuals were studied: 217 with beta thalassaemia trait, of whom 154 were awar...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2008.07071.x
更新日期:2008-05-01 00:00:00
abstract::Platelet mass (mean platelet volume x platelet count) can be derived from data obtained from the routine full blood count and separates patients with myelodysplastic syndromes (MDS) at diagnosis into three distinct prognostic groups: low platelet mass group - median survival 5 months and 5-year survival 0%; intermedia...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06246.x
更新日期:2006-10-01 00:00:00
abstract::We studied 13 patients with rheumatoid arthritis (RA) and gold-induced thrombocytopenia. Platelet-specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb07528.x
更新日期:1986-07-01 00:00:00
abstract::Serum antiplatelet IgG and platelet-associated IgG (PAIgG) were studied in 68 AIDS-free human immunodeficiency virus (HIV)-infected patients with severe immunologic thrombocytopenic purpura (ITP), for the presence of platelet autoantibodies. Serum IgG with antiplatelet activity was found in 72% of the sera. However, t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb00259.x
更新日期:1989-10-01 00:00:00
abstract::The haematological and immunological characteristics of 34 healthy anti-HTLV-I antibody-positive individuals (HTLV-I carriers) in southwestern Japan were examined. No significant difference was noted between carriers and the controls in counts of RBC, WBC and the absolute number of lymphocytes. The serum IgG in the ca...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb07587.x
更新日期:1986-09-01 00:00:00
abstract::We report the results of consecutive tests in nine BCR-ABL-positive ALL patients by one-step and two-step (nested primer) reverse transcriptase-polymerase chain reaction (RT-PCR). Six patients could be tested in complete haematological remission (CHR). One patient remained one-step positive; four patients became one-s...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb08444.x
更新日期:1995-04-01 00:00:00
abstract::The clinico-pathological features of 12 cases of malignant histiocytosis (histiocytic medullary reticulosis), aged 12-60 years, were studied. Special emphasis was put on the analysis of the haematological, cytological and histopathological findings of the disease. Bone marrow aspirates and biopsies from involved tissu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb03640.x
更新日期:1978-09-01 00:00:00
abstract::The replicative potential of human CD56(+) CD3(-) natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4-1BB ligand and interleukin 15 (K562-mb15-41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged fr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07667.x
更新日期:2009-06-01 00:00:00
abstract::Acute graft-versus-host disease (GVHD) remains a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The emergence of different immuno-prophylaxis strategies, such as post-transplant cyclophosphamide or anti-thymocyteglobulin has reduced the incidence of acute GVHD in recent years...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.16190
更新日期:2019-12-01 00:00:00
abstract::Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb02531.x
更新日期:1990-01-01 00:00:00
abstract::Megakaryopoiesis was examined in 10 patients (eight females and two males) with cyclic thrombocytopenia (CT) to investigate the underlying pathogenesis. Numbers of CFU-Meg and megakaryocytes and the mean cytoplasmic area (mean area) of megakaryocytes at the peak, nadir, ascent mid phase, and descent mid phase of the p...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05267.x
更新日期:1995-09-01 00:00:00
abstract::Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13782
更新日期:2015-12-01 00:00:00
abstract::The in vitro efficacies of three new drugs--clofarabine (CLOF), nelarabine (NEL) and flavopiridol (FP) - were assessed in a panel of acute lymphoblastic leukaemia (ALL) cell lines. The 50% inhibitory concentration (IC50) for CLOF across all lines was 188-fold lower than that of NEL. B-lineage, but not T-lineage lines,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06527.x
更新日期:2007-04-01 00:00:00
abstract::In a randomized study that compared human leucocyte antigen-identical allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) versus bone marrow (BM) transplantation, the expression of activation markers, CD23, CD25 and CD45RO by B cells, was compared in blood before and af...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2141.2001.02965.x
更新日期:2001-09-01 00:00:00
abstract::Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' un...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.14913
更新日期:2017-11-01 00:00:00
abstract::Long term outcomes and mutations in patients with mantle cell lymphoma (MCL) who discontinued ibrutinib have not been described. Using deep targeted next generation sequencing, we performed somatic mutation profiling from 15 MCL patients (including 5 patients with paired samples; before and after progression on ibruti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15567
更新日期:2018-11-01 00:00:00
abstract::Serum concentrations of the thrombopoiesis-enhancing cytokines thrombopoietin (TPO), erythropoietin (EPO), interleukin (IL)-6 and IL-11 were determined in 119 healthy whole-blood (WBD) and 101 platelet donors (PD) prior to donation. The 90% TPO reference interval in WBD of 64-867 pg/ml (median 163, 100% range 45-7572)...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1999.01328.x
更新日期:1999-05-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological character...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2005.05716.x
更新日期:2005-10-01 00:00:00
abstract::A novel mutation of the N-RAS gene of T-ALL blast cells was detected by a direct sequencing of in vitro amplified exon-1 of the N-RAS gene. Threonine (ACA) was substituted for alanine (GCA) at codon 11. This mutation would have been overlooked by conventional probe hybridization techniques. A search for other mutation...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb07648.x
更新日期:1989-05-01 00:00:00
abstract::In this study we have carried out haplotype analysis at the beta-globin gene cluster and defined the beta-thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a beta-thalassaemia allele characterized by microcytosis, hypoch...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb02331.x
更新日期:1987-10-01 00:00:00
abstract::Interleukin-6 (IL6) plays a central role in multiple myeloma pathogenesis and confers resistance to corticosteroid-induced apoptosis. We therefore evaluated the efficacy and safety of siltuximab, an anti-IL6 monoclonal antibody, alone and in combination with dexamethasone, for patients with relapsed or refractory mult...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.12266
更新日期:2013-05-01 00:00:00