Abstract:
:Antibody-mediated rejection (AMR) is a major risk factor for graft loss following kidney transplantation. Traditional anti-humoral therapies provide suboptimal therapy and they do not deplete plasma cells, which are the source of antibody production. Proteasome inhibitors (PI) have been shown to deplete both transformed and nontransformed plasma cells in human transplant recipients and animal models; and therefore, offer a new paradigm for AMR, ie, plasma cell-targeted therapy. Bortezomib, a first in class proteasome inhibitor approved by the US Food and Drug Administration for treatment of multiple myeloma, has been used to treat AMR in several solid organ transplant recipients. The greatest experience with PI therapy for treating AMR is in kidney transplant recipients. Experiences to date with PI therapy have demonstrated that: (1) early AMR (within the first 6 months post-transplant) responds better than late AMR, and (2) the nature of the plasma cell clonal population influences sensitivity to PI therapy with plasma subsets greater than long-lived bone marrow niche-resident plasma cells. In conclusion, plasma cell-targeted therapy with PIs is a method for targeting plasma cells (the source of antibody production) with a well-elucidated mechanism of action and subsequent points of synergy, thereby providing an exciting new potential means for enhancing anti-humoral therapies.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Sadaka B,Alloway RR,Shields AR,Schmidt NM,Woodle ESdoi
10.1053/j.seminhematol.2012.04.008subject
Has Abstractpub_date
2012-07-01 00:00:00pages
263-9issue
3eissn
0037-1963issn
1532-8686pii
S0037-1963(12)00031-5journal_volume
49pub_type
杂志文章,评审abstract::Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undete...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2010.11.009
更新日期:2011-01-01 00:00:00
abstract::Imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ; Glivec, Novartis Pharma AG, Basel, Switzerland), a signal transduction inhibitor with preferential effects against the tyrosine kinase activity of the protein product of the ABL proto-oncogene, induced hematologic responses in >or=90% of pati...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.36927
更新日期:2002-10-01 00:00:00
abstract::Severe neutropenia renders patients susceptible to life-threatening bacterial and fungal infections. Despite improvements in supportive care and antimicrobial therapy, morbidity and mortality remains significant. Since the 1960s, granulocyte transfusions have been used to either treat or prevent serious infections in ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2019.11.002
更新日期:2019-10-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a complex and heterogeneous disease with distinct age-associated genomic and epigenomic alterations. A large number of somatic karyotypic and molecular alterations have been identified in AML to date; however, very few predict outcome or identify potential therapeutic targets. Here we d...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2013.09.003
更新日期:2013-10-01 00:00:00
abstract::Imatinib (Gleevec) (formerly STI571) is an orally bioavailable rationally developed inhibitor of the tyrosine kinases Bcr-Abl, Kit, and platelet-derived growth factor receptor (PDGFR). In 4 years of clinical development, more than 12,000 patients have been treated in the clinical development program. Imatinib was firs...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2003.50037
更新日期:2003-04-01 00:00:00
abstract::Hemangiomas and lymphangiomas are two main types of angiomatous disease that occur most commonly in infancy and childhood. Most hemangiomas resolve spontaneously, but some endanger vital structures such as the lung, as in pulmonary hemangiomatosis, a rare and universally fatal disease. Occasionally, hemangiomatous les...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1990-07-01 00:00:00
abstract::The past decade has seen improvements in overall survival (OS) for patients with the two most common lymphoma histologies: diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, at least four independent datasets have confirmed these survival improvements. The monoclonal antibody rituximab has sign...
journal_title:Seminars in hematology
pub_type:
doi:10.1053/j.seminhematol.2008.02.005
更新日期:2008-04-01 00:00:00
abstract::The prolonged and severe myelosuppression associated with high-dose chemotherapy and autologous bone marrow transplantation is a major causative factor in patient morbidity and mortality resulting from infection and other causes. The recent molecular cloning, in vitro expression, and formulation of recombinant human c...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Large scale sequencing projects over the past 2 decades have led to the identification of many common genomic alterations in hematolymphoid neoplasms, some of which with diagnostic, therapeutic, and prognostic implications [1-3]. Although these alterations can be tested individually with high sensitivity and specifici...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2018.05.006
更新日期:2019-01-01 00:00:00
abstract::The successful clinical development of thalidomide, bortezomib, and lenalidomide not only transformed the therapeutic management of multiple myeloma (MM) but also catalyzed a renewed interest in the development of additional classes of novel agents for this disease. This review focuses on a series of new therapeutics ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2009.02.003
更新日期:2009-04-01 00:00:00
abstract::Seventy-six patients with previously untreated advanced Hodgkin's disease have been treated with the MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vincristine) hybrid program. Ten patients also received involved field radiation to the mediastinum for residual nodal disease af...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administr...
journal_title:Seminars in hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (kn...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract::Hydroxyurea (HU) is the first widely used treatment to have an impact on the severity of disease in adult patients with sickle cell anemia, but limited data are available for younger patients or those with variant genotypes. We reviewed 324 months of experience with HU in 16 patients from 5.3 to 18.4 years of age trea...
journal_title:Seminars in hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::The central hypothesis of our laboratory research program in large granular lymphocyte (LGL) leukemia is that leukemic LGL represent antigen-driven cytotoxic T lymphocytes (CTL) with characteristics of dysregulated apoptosis. The clinical features of LGL leukemia highlight the association of autoimmune diseases such a...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(03)00135-5
更新日期:2003-07-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is probably the best understood human malignancy at the molecular level, but among the hardest to explain to patients concerning appropriate treatment options. At present, we do not know the long-term outcome of promising new therapies such as the tyrosine kinase inhibitor imatinib mesyl...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90116-7
更新日期:2001-07-01 00:00:00
abstract::While the prevalence of iron deficiency has remained relatively constant, there has been continuing refinement in its laboratory recognition, especially with the recent introduction of serum ferritin and FEP measurements. It is helpful to classify iron deficiency into three stages. Storage iron depletion is identified...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1982-01-01 00:00:00
abstract::Peripheral suppression of autoreactive T cells by specialized T-cell populations is one of several mechanisms ensuring self-tolerance within the adaptive immune system. Thymus-derived CD4+CD25+ T cells expressing the transcriptional repressor FOXP3 mediate such immunoregulatory functions and are pivotal for the preven...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.09.006
更新日期:2006-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2007.10.006
更新日期:2008-01-01 00:00:00
abstract::Current therapeutic strategies for autoimmune diseases primarily rely on immunosuppression, but global immune suppression results in an increased risk for severe infection and malignancy. In contrast, immuomodulation is another therapeutic approach employing intrinsic or environmental regulators that exert modulatory ...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2016.04.009
更新日期:2016-04-01 00:00:00
abstract::Idiopathic thrombocytopenic purpura (ITP) is an illness of primary acquired thrombocytopenia occurring in the absence of marrow failure. Splenectomy was first used as a treatment for ITP in 1913. However, with the realization that opsonin (critical for the optimal killing of invasive micro-organisms by white blood cel...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90114-8
更新日期:2000-01-01 00:00:00
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journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90036-2
更新日期:2000-04-01 00:00:00
abstract::Endogenous thrombopoietin (TPO) stimulates platelet production in nonhuman primates by inducing dose-dependent megakaryocyte development from early marrow hematopoietic progenitors and subsequent proliferation and endoreduplication. In nonhuman primates, recombinant human TPO, nonpegylated or pegylated rHu megakaryocy...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-07-01 00:00:00
abstract::While cure rates of over 80% are achieved in contemporary pediatric acute lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their disease, and little progress has been made in the treatment of refractory and relapsed ALL. Moreover, the burden of therapy is high in a significant number of newly di...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2008.09.009
更新日期:2009-01-01 00:00:00
abstract::From work particularly In the last two decades of the century, the cell populations forming blood cells can now be purified and cultured clonally so that blood cell formation can be analyzed in vitro. A large number of specific regulators of this process have been identified and mass-produced in recombinant form. Thre...
journal_title:Seminars in hematology
pub_type: 历史文章,杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myelocytic leukemia (AML). With the exception of allogeneic stem cell transplantation, there is generally no curative treatment for these d...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.02.002
更新日期:2004-04-01 00:00:00
abstract::Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.10.009
更新日期:2012-01-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is a clonal proliferation of mature-appearing, but maturationally immature B cells; T cells are rarely involved. Most data suggest that CLL cells are frozen at an early step in maturation; this can be overcome by several techniques such as in vitro incubation with tumor promotors. Al...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1987-10-01 00:00:00
abstract::A new high-purity recombinant factor VIII preparation has been developed for the treatment of hemophilia A. Structurally, this factor VIII preparation, B-domain deleted recombinant factor VIII (BDDrFVIII), differs from other recombinant and plasma-derived factor VIII preparations in that most of the B-domain has been ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90103-9
更新日期:2001-04-01 00:00:00
abstract::Thrombosis is a common and potentially serious complication of immune-mediated heparin-induced thrombocytopenia (HIT). Discontinuation of heparin is a simple and important maneuver in patients with suspected HIT. Unfortunately, thrombosis often occurs even in those patients in whom heparin was discontinued because of ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00