HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism.


:The finding that the risk of relapse in hematologic malignancy decreases after allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is considered to be frequently offset by graft-versus-host disease (GVHD). Thus, improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This cohort study registered 4643 patients with hematologic malignancies who received transplants from unrelated donors. Six major human leukocyte antigen (HLA) loci were retrospectively genotyped. We identified 4 HLA-Cw and 6 HLA-DPB1 mismatch combinations responsible for a decreased risk of relapse; of these, 8 of 10 combinations were different from those responsible for severe acute GVHD, including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of HLA-DPB1 were associated with a significantly better overall survival than were completely matched pairs. Moreover, several amino acid substitutions on specific positions responsible for a decreased risk of relapse were identified in HLA-Cw, but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism of the decreased risk of relapse on the basis of HLA molecule. Donor selection made in consideration of these results might allow the separation of GVL from acute GVHD, especially in HLA-DPB1 mismatch combinations.






Kawase T,Matsuo K,Kashiwase K,Inoko H,Saji H,Ogawa S,Kato S,Sasazuki T,Kodera Y,Morishima Y,Japan Marrow Donor Program.




Has Abstract


2009-03-19 00:00:00
















  • Marrow harvesting from normal donors.

    abstract::The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties wer...


    pub_type: 杂志文章


    authors: Buckner CD,Clift RA,Sanders JE,Stewart P,Bensinger WI,Doney KC,Sullivan KM,Witherspoon RP,Deeg HJ,Appelbaum FR

    更新日期:1984-09-01 00:00:00

  • Cytolytically inactive terminal complement complex causes transendothelial migration of polymorphonuclear leukocytes in vitro and in vivo.

    abstract::Intravital microscopy was used to monitor leukocyte traffic across rat mesenteric postcapillary venules induced by the inactive terminal complement (C) complex (iTCC) topically applied to ileal mesentery. Leukocytes started rolling within 15 minutes from the administration of iTCC, and by 1 hour they adhered almost co...


    pub_type: 杂志文章


    authors: Dobrina A,Pausa M,Fischetti F,Bulla R,Vecile E,Ferrero E,Mantovani A,Tedesco F

    更新日期:2002-01-01 00:00:00

  • Plasma crosslinked fibrin polymers: quantitation based on tissue plasminogen activator conversion to D-dimer and measurement in normal and patients with acute thrombotic disorders.

    abstract::Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo hemostatic activation and are elevated in thrombotic disease. We have investigated the plasmic degradation of plasma XLFP in vitro to provide information regarding the pattern of crosslinking and the composition of degradation products. Plasma...


    pub_type: 杂志文章


    authors: Kornberg A,Francis CW,Marder VJ

    更新日期:1992-08-01 00:00:00

  • Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors.

    abstract::Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation fac...


    pub_type: 杂志文章


    authors: Leberbauer C,Boulmé F,Unfried G,Huber J,Beug H,Müllner EW

    更新日期:2005-01-01 00:00:00

  • Second to none.

    abstract::In this issue of Blood, Usmani et al provide important information on second primary malignancies in patients treated with thalidomide and lenalidomide in the Arkansas total therapy trials. ...


    pub_type: 评论,杂志文章


    authors: Rajkumar SV

    更新日期:2012-08-23 00:00:00

  • Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer.

    abstract::A 64-yr-old female developed acute myeloblastic leukemia following radiation and drug therapy for colon carcinoma. The patient was heterozygous for glucose-6-phosphate dehydrogenase (G-6-PD) and displayed types A and B isoenzymes in nonhematopoietic tissue. In contrast, only type B G-6-PD was observed in peripheral bl...


    pub_type: 杂志文章


    authors: Wiggans RG,Jacobson RJ,Fialkow PJ,Woolley PV 3rd,Macdonald JS,Schein PS

    更新日期:1978-10-01 00:00:00

  • Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU.

    abstract::Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have l...


    pub_type: 杂志文章


    authors: Gerson SL,Phillips W,Kastan M,Dumenco LL,Donovan C

    更新日期:1996-09-01 00:00:00

  • Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production.

    abstract::Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study,...


    pub_type: 杂志文章


    authors: Choi YS,Choi HJ,Min JK,Pyun BJ,Maeng YS,Park H,Kim J,Kim YM,Kwon YG

    更新日期:2009-10-01 00:00:00

  • EZH2 mutational status predicts poor survival in myelofibrosis.

    abstract::We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with postpolycythemia vera/postessential thrombocythemia (PPV/PET) MF for mutations of EZH2. Mutational status at diagnosis was correlated with hematologic parameters, clinical manifestations, and outcome. A total of 25 different EZH2 mutations were de...


    pub_type: 杂志文章


    authors: Guglielmelli P,Biamonte F,Score J,Hidalgo-Curtis C,Cervantes F,Maffioli M,Fanelli T,Ernst T,Winkelman N,Jones AV,Zoi K,Reiter A,Duncombe A,Villani L,Bosi A,Barosi G,Cross NC,Vannucchi AM

    更新日期:2011-11-10 00:00:00

  • Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells.

    abstract::Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not only accelerates aggregation of platelets but also is known to promote mitosis, migration, and contraction of vascular smooth muscle cells (VSMCs). These effects are considered to contribute to thrombus formation and atherosclerosis. The ...


    pub_type: 杂志文章


    authors: Kawano H,Tsuji H,Nishimura H,Kimura S,Yano S,Ukimura N,Kunieda Y,Yoshizumi M,Sugano T,Nakagawa K,Masuda H,Sawada S,Nakagawa M

    更新日期:2001-03-15 00:00:00

  • Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment.

    abstract::A retrospective study compared posttransplant engraftment parameters in 203 patients with myelofibrosis (MF) with those in a population of 203 matched controls without MF. There were no significant differences between these groups in the proportions of patients who died without achieving engraftment and in the disease...


    pub_type: 杂志文章


    authors: Soll E,Massumoto C,Clift RA,Buckner CD,Appelbaum FR,Storb R,Sale G,Hackman R,Martin P

    更新日期:1995-12-15 00:00:00

  • Chronic myelodysplastic syndrome (preleukemia) with the Philadelphia chromosome.

    abstract::A patient with severe anemia, reticulocytopenia, and erythroid hyperplasia of the bone marrow developed fatal acute nonlymphocytic leukemia after 3 yr. A Philadelphia chromosome with the typical 9/22 translocation t(9q +;22q-) was identified by banding techniques in a small number of bone marrow cells throughout the p...


    pub_type: 杂志文章


    authors: Roth DG,Richman CM,Rowley JD

    更新日期:1980-08-01 00:00:00

  • The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element.

    abstract::Cellular interleukin 6 (IL-6) is an important growth factor for Kaposi sarcoma- associated herpesvirus (KSHV)-associated neoplasms, which include human immunodeficiency virus (HIV)-related and -unrelated cases of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Increased ...


    pub_type: 杂志文章


    authors: An J,Lichtenstein AK,Brent G,Rettig MB

    更新日期:2002-01-15 00:00:00

  • Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor.

    abstract::The cellular and molecular events underlying the formation and differentiation of mesoderm to derivatives such as blood are critical to our understanding of the development and function of many tissues and organ systems. How different mesodermal populations are set aside to form specific lineages is not well understoo...


    pub_type: 杂志文章


    authors: Willey S,Ayuso-Sacido A,Zhang H,Fraser ST,Sahr KE,Adlam MJ,Kyba M,Daley GQ,Keller G,Baron MH

    更新日期:2006-04-15 00:00:00

  • Alphastatin, a 24-amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo.

    abstract::Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24-amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed "alphastatin") has potent antiangioge...


    pub_type: 杂志文章


    authors: Staton CA,Brown NJ,Rodgers GR,Corke KP,Tazzyman S,Underwood JC,Lewis CE

    更新日期:2004-01-15 00:00:00

  • Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group.

    abstract::To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cel...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Williamson LM,Wimperis JZ,Williamson P,Copplestone JA,Gooi HC,Morgenstern GR,Norfolk DR

    更新日期:1994-05-15 00:00:00

  • Functional study of lipids of PNH red cell membranes: susceptibility of liposomes to reactive lysis.

    abstract::Lipids extracted with chloroform-methanol from red blood cell membranes of 7 PNH and 13 control subjects were used for the preparation of liposomes, which were then examined with the reactive lysis test. PNH liposomes lysed to a higher extent than control liposomes as indicated by the higher dilution of the limiting c...


    pub_type: 杂志文章


    authors: Tedesco F,Kahane I,Zanella A,Giovanetti AM,Sirchia G

    更新日期:1981-05-01 00:00:00

  • Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities.

    abstract::Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis vir...


    pub_type: 杂志文章,评审


    authors: Marcucci F,Mele A

    更新日期:2011-02-10 00:00:00

  • Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen.

    abstract::Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure resulting from vascular leakage are often observed in these severe conditions. In the prese...


    pub_type: 杂志文章


    authors: Oehmcke S,Shannon O,von Köckritz-Blickwede M,Mörgelin M,Linder A,Olin AI,Björck L,Herwald H

    更新日期:2009-07-09 00:00:00

  • Cellular response to hypoxia involves signaling via Smad proteins.

    abstract::The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream ...


    pub_type: 杂志文章


    authors: Zhang H,Akman HO,Smith EL,Zhao J,Murphy-Ullrich JE,Batuman OA

    更新日期:2003-03-15 00:00:00

  • Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy.

    abstract::From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved. No manipulations to increase the number of stem cells circulating in the blood were used during the col...


    pub_type: 杂志文章


    authors: Kessinger A,Armitage JO,Landmark JD,Smith DM,Weisenburger DD

    更新日期:1988-03-01 00:00:00

  • An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is a major unmet medical need. Most patients have poor long-term survival, and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T cells by binding to CD3, the signaling component of the T-cell receptor, an...


    pub_type: 杂志文章


    authors: Leong SR,Sukumaran S,Hristopoulos M,Totpal K,Stainton S,Lu E,Wong A,Tam L,Newman R,Vuillemenot BR,Ellerman D,Gu C,Mathieu M,Dennis MS,Nguyen A,Zheng B,Zhang C,Lee G,Chu YW,Prell RA,Lin K,Laing ST,Polson AG

    更新日期:2017-02-02 00:00:00

  • Mode of action of iron (III) chelators as antimalarials: I. Membrane permeation properties and cytotoxic activity.

    abstract::We have designed two subfamilies of lipophilic iron (III) chelators previously termed reversed siderophores (RSFs). The agents display physicochemical properties that favor extraction of iron beyond membrane barriers of Plasmodium falciparum-infected red blood cells. We studied the in vitro antimalarial potency of RSF...


    pub_type: 杂志文章


    authors: Lytton SD,Mester B,Dayan I,Glickstein H,Libman J,Shanzer A,Cabantchik ZI

    更新日期:1993-01-01 00:00:00

  • Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.

    abstract::Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215,...


    pub_type: 杂志文章


    authors: Santo L,Hideshima T,Kung AL,Tseng JC,Tamang D,Yang M,Jarpe M,van Duzer JH,Mazitschek R,Ogier WC,Cirstea D,Rodig S,Eda H,Scullen T,Canavese M,Bradner J,Anderson KC,Jones SS,Raje N

    更新日期:2012-03-15 00:00:00

  • Activated protein C inhibits high mobility group box 1 signaling in endothelial cells.

    abstract::A pathogenic role for high-mobility group box 1 (HMGB1) protein has been postulated in severe sepsis. Activated protein C (APC) is the only drug approved by the Food and Drug Administration for severe sepsis; however, its effect on HMGB1 signaling has never been investigated. Here, we monitored the effect of APC on th...


    pub_type: 杂志文章


    authors: Bae JS,Rezaie AR

    更新日期:2011-10-06 00:00:00

  • Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia.

    abstract::We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allo...


    pub_type: 杂志文章


    authors: McGlave PB,Miller WJ,Hurd DD,Arthur DC,Kim T

    更新日期:1981-11-01 00:00:00

  • Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

    abstract::In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were...


    pub_type: 杂志文章,多中心研究


    authors: Cavé H,Suciu S,Preudhomme C,Poppe B,Robert A,Uyttebroeck A,Malet M,Boutard P,Benoit Y,Mauvieux L,Lutz P,Méchinaud F,Grardel N,Mazingue F,Dupont M,Margueritte G,Pages MP,Bertrand Y,Plouvier E,Brunie G,Bastard C,P

    更新日期:2004-01-15 00:00:00

  • Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations.

    abstract::Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL m...


    pub_type: 杂志文章


    authors: Müller MC,Cortes JE,Kim DW,Druker BJ,Erben P,Pasquini R,Branford S,Hughes TP,Radich JP,Ploughman L,Mukhopadhyay J,Hochhaus A

    更新日期:2009-12-03 00:00:00

  • Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations.

    abstract::The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hep...


    pub_type: 杂志文章


    authors: Dallalio G,Law E,Means RT Jr

    更新日期:2006-04-01 00:00:00

  • Ibrutinib: a force with a dark side?

    abstract::In this issue of Blood, Martin et al report poor outcomes for ibrutinib-refractory patients with mantle cell lymphoma (MCL). MCL, an uncommon B-cell lymphoma driven by dysregulated cyclin D1, responds well to initial therapy but is destined to relapse. Subsequent single-agent treatments had modest response rates and d...


    pub_type: 评论,杂志文章


    authors: Smith MR

    更新日期:2016-03-24 00:00:00