Abstract:
:T-cell depletion (TCD) of the donor marrow graft has been shown to reduce the severity of graft-versus-host disease (GVHD) in patients with chronic-phase (CP) chronic myelogenous leukemia (CML) undergoing HLA-identical sibling allogeneic marrow transplantation. However, there has been a corresponding reduction in the graft-versus-leukemia effect so that any decrease in GVHD-related mortality has been offset by an increased rate of disease relapse. Therapy of recurrent disease with donor leukocyte infusions (DLI) has been proven to be effective salvage therapy for the majority of patients who relapse after allogeneic BMT with CP CML. However, the overall impact of salvage DLI therapy on the survival of CP CML patients initially transplanted with TCD marrow grafts is not defined. To address this question, we have evaluated a clinical strategy of TCD followed by targeted adoptive immunotherapy with DLI in 25 CP CML patients undergoing allogeneic BMT from HLA-identical siblings. All patients received a standardized preparative regimen along with ex vivo TCD and posttransplant cyclosporine as GVHD prophylaxis. Durable engraftment was observed in all 25 patients. The incidence of grade II to IV acute GVHD was 8%. The cumulative incidence of transplant-related mortality (TRM) was 4%, and the 1-year probability of overall survival was 96%. The 3-year cumulative relapse incidence was 49%. All relapsed patients received DLI to reinduce remission. The total T-cell dose administered to these patients varied from 0.1 to 5.0 x 10(8) T cells/kg. Complete responses were observed in 12 of 14 patients, with 1 additional patient still too early to evaluate. Three patients died of GVHD after DLI, and 1 relapsed into blast crisis after a transient cytogenetic remission. Of the remaining 10 patients, 8 are in molecular remission, 1 is alive in relapse, and 1 is receiving DLI treatment. The median follow-up after infusion of surviving DLI patients in remission is 5.3 years. The probability of overall 5-year survival for the entire population is 80%, with a median follow-up of 6.4 years. We conclude that the clinical strategy of TCD followed by targeted adoptive immunotherapy with DLI for those patients with evidence of recurrent disease is a viable transplant strategy for CP CML, resulting in 80% survival and a low risk of acute GVHD and transplant-related mortality.
journal_name
Bloodjournal_title
Bloodauthors
Drobyski WR,Hessner MJ,Klein JP,Kabler-Babbitt C,Vesole DH,Margolis DA,Keever-Taylor CAsubject
Has Abstractpub_date
1999-07-15 00:00:00pages
434-41issue
2eissn
0006-4971issn
1528-0020journal_volume
94pub_type
杂志文章相关文献
BLOOD文献大全abstract::An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-02-0490
更新日期:2004-01-01 00:00:00
abstract::The murine Ly6-E gene is transcriptionally induced by interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma in a variety of distinct cell types. The mechanism of IFN inducibility in B-cell lines was investigated by deletion analysis of the promoter and by identifying DNA binding proteins in mobility shift assays. A reg...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecul...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-07-167106
更新日期:2009-03-26 00:00:00
abstract::Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood.v97.5.1196
更新日期:2001-03-01 00:00:00
abstract::In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 p...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1999-08-15 00:00:00
abstract::Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::Human immunodeficiency virus-1 (HIV-1)-Tat, the transactivating gene product of HIV-1, has been shown to interact with different cell types, inducing gene expression, altering their growth and migratory behavior. In this study we examined whether Tat might affect functions of acquired immunodeficiency syndrome (AIDS)-...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::An abnormal von Willebrand factor (vWF) gene restriction pattern has been found in a patient with von Willebrand disease. Because this gene alteration is not present in his parents or in 50 normal and 25 affected subjects, and the restriction fragment length polymorphism haplotypes are inherited normally in the patien...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::In the current study, we investigated whether the naive, poly I:C or interleukin-2 (IL-2)-induced natural killer (NK)/lymphokine-activated killer (LAK) cells use perforin and/or Fas ligand (FasL) to mediated cytotoxicity. We correlated these findings with the ability of mice to reject syngeneic Fas+ and Fas- tumor cel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::We here report the initiation of hematopoietic recovery in congenitally hypoplastic S1/S1d mice by the cytotoxic ablation of cells bearing the natural killer (NK) phenotype (NK 1.1+). The most striking finding was the early several-fold increase in the cycling fraction of stem and progenitor cells (with the exception ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-09-15 00:00:00
abstract::Stem cell factor (SCF) and interleukin-3 (IL-3) both act on several target hematopoietic populations, including mast cells. We have isolated a unique murine mast cell line, B6M, that is phenotypically similar to immature mast cells. For B6M cells, IL-3 is a survival factor and alone does not stimulate proliferation. S...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P), a bioactive lipid, is produced and stored in platelets and is released from activated platelets during blood coagulation activation. Thrombin, which is also generated during blood coagulation, has been shown to induce tissue factor (TF), the initiator of blood coagulation, in endothelial...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3607
更新日期:2003-09-01 00:00:00
abstract::In mouse mid-gestational embryos, definitive hematopoietic stem progenitor cells are derived directly from a very small proportion of the arterial endothelium. However, the physiological mechanisms restraining excessive endothelial-hematopoietic transition remain elusive. We show here that genetic deletion of Smad4 fr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-09-526053
更新日期:2014-04-03 00:00:00
abstract::Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methio...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::We investigated the in vivo effects of erythropoietin (EPO) on granulopoiesis and, conversely, the effect of granulocyte colony-stimulating factor (G-CSF) treatment on erythropoiesis. Recombinant human EPO at four different doses in combination with recombinant human G-CSF also at four different doses was simultaneous...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thrombomodulin complex. Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality before embryonic day 10 (E10.0). EPCR is detected in the giant trophoblast cells at the feto-maternal boundary from E7.5 and weakly...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-01-0406
更新日期:2005-10-15 00:00:00
abstract::We report 2 new mutations identified in 3 patients and characterized by the markedly decreased affinity of von Willebrand factor (vWF) for factor VIII (FVIII). Patients 2 and 3, who have a typical type 2N phenotype, were found to be compound heterozygous for Arg91Gln and Cys25Tyr or Cys95Phe, respectively. Patient 1, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-05-15 00:00:00
abstract::We have previously determined that in African sickle cell anemia (SS) patients three different beta-like globin gene cluster haplotypes are associated with different percent G gamma (one of the two types of non-alpha chains comprising hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now that i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-03-15 00:00:00
abstract::We report in this paper that a novel small molecule, JTZ-132, induced growth and differentiation of megakaryocytic progenitor cells and improved thrombocytopenia in myelosuppressed mice. JTZ-132 stimulated proliferation of UT-7/TPO cells, a cell line highly sensitive to thrombopoietin (TPO), and exhibited full efficac...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-10-3623
更新日期:2004-07-01 00:00:00
abstract::Among the most striking morphological features of acute nonlymphoblastic leukemias (ANLL) is the occurrence of eosinophilic cytoplasmic inclusions known as Auer rods on Auer bodies. We examined immature myeloid cells from the peripheral blood of 9 human fetuses of 16-19 wk gestation for the presence of such structures...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of F...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Interleukin-15 (IL-15) induces proliferation and promotes cell survival of human T and B lymphocytes, natural killer cells, and neutrophils. Here we report the constitutive expression of a functional IL-15 receptor (IL-15R) in 6 of 6 myeloma cell lines and in CD38(high)/CD45(low )plasma cells belonging to 14 of 14 pat...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-343962
更新日期:2011-12-22 00:00:00
abstract::Leukocyte transendothelial migration (TEM) is a critical event during inflammation. CD47 has been implicated in myeloid cell migration across endothelium and epithelium. CD47 binds to signal regulatory protein (SIRP), SIRPalpha and SIRPgamma. So far, little is known about the role of endothelial CD47 in T-cell TEM in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-01-134429
更新日期:2008-08-15 00:00:00
abstract::The zinc finger transcription factor GATA-2 is highly expressed in immature hematopoietic cells and declines with blood cell maturation. To investigate its role in normal adult hematopoiesis, a bicistronic retroviral vector encoding GATA-2 and the green fluorescent protein (GFP) was used to maintain the high levels of...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly cross-linked hemoglobin-based oxygen carrier being developed as a therapy for acute blood loss. We report here the absence of immunogenicity of DCLHb in patients enrolled in phase II and III clinical trials of DCLHb. Two very sensitive immunoassays, an e...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-01-15 00:00:00
abstract::The anticoagulant warfarin has >30 million prescriptions per year in the United States. Doses can vary 20-fold between patients, and incorrect dosing can result in serious adverse events. Variation in warfarin pharmacokinetic and pharmacodynamic genes, such as CYP2C9 and VKORC1, do not fully explain the dose variabili...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-04-568436
更新日期:2014-10-02 00:00:00
abstract::Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Complement plays a key role in host defense, but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins, including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-07-728253
更新日期:2017-03-02 00:00:00
abstract::Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic bone marrow transplantation (BMT). The identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most poten...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-04-1082
更新日期:2002-10-01 00:00:00