Fludarabine induces growth arrest and apoptosis of cytokine- or alloantigen-stimulated peripheral blood mononuclear cells, and decreases production of Th1 cytokines via inhibition of nuclear factor kappaB.

Abstract:

:Fludarabine is a purine analog that has demonstrated significant activity in B-cell malignancies, including CLL. Fludarabine also possesses an immunosuppressive effect and is being used to prevent GVHD in hematopoietic stem cell transplantation. However, the molecular mechanism by which fludarabine inhibits immunoreaction remains to be fully elucidated. This study found that fludarabine inhibited tumor necrosis factor alpha (TNF-alpha)-stimulated degradation of IkappaBalpha, resulting in blockade of nuclear translocation of nuclear factor kappaB (NF-kappaB) in Jurkat T cells, as measured by western blot analysis and immunocytochemistry. The ability of fludarabine to inhibit NF-kappaB was further confirmed by electrophoretic mobility shift assay. We also found that fludarabine induced growth arrest and apoptosis of alloreactive and TNF-alpha-stimulated PBMCs. In addition, fludarabine inhibited TNF-alpha-stimulated production of IL-2 and IFN-gamma, which play important roles in the onset of GVHD, in Jurkat cells. Taken together, fludarabine is useful for management of immune diseases, including GVHD, through inactivation of NF-kappaB.

journal_name

Bone Marrow Transplant

authors

Nishioka C,Ikezoe T,Togitani K,Yokoyama A

doi

10.1038/sj.bmt.1705901

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

303-9

issue

3

eissn

0268-3369

issn

1476-5365

pii

1705901

journal_volume

41

pub_type

杂志文章
  • Improving cord blood typing with next-generation sequencing: impact of allele-level HLA and NIMA determination on their selection for transplantation.

    abstract::Allele-level HLA compatibility in cord blood transplantation, together with noninherited maternal antigen or NIMA matching, have been associated with better transplant outcomes. The aim of this work is to develop a cost-efficient high-resolution HLA typing strategy based on next-generation sequencing to improve the qu...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/s41409-020-0890-9

    authors: Enrich E,Vidal F,Corrales I,Campos E,Borràs N,Martorell L,Sánchez M,Querol S,Rudilla F

    更新日期:2020-08-01 00:00:00

  • Second EBMT Workshop on reduced intensity allogeneic hemopoietic stem cell transplants (RI-HSCT).

    abstract::A second meeting on reduced intensity allogeneic stem cell transplants (RI-HSCT) was convened in Zurich in February 2001 and focused on transplant-related mortality (TRM) and graft-versus-host disease (GVHD). Retrospective and prospective studies from the EBMT, national groups and single institutions included over 900...

    journal_title:Bone marrow transplantation

    pub_type: 共识发展会议,杂志文章,评审

    doi:10.1038/sj.bmt.1703355

    authors: Bacigalupo A

    更新日期:2002-02-01 00:00:00

  • Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies.

    abstract::We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/s41409-019-0726-7

    authors: Peric Z,Mohty R,Bastos J,Brissot E,Battipaglia G,Belhocine R,Sestili S,Giannotti F,Vekhoff A,Ledraa T,Legrand O,Lapusan S,Isnard F,Labopin M,Bonnin A,Mediavilla C,Rubio MT,Ruggeri A,Duléry R,Malard F,Mohty M

    更新日期:2020-04-01 00:00:00

  • The use of locus-specific minisatellite probes to check engraftment following allogeneic bone marrow transplantation for severe combined immunodeficiency disease.

    abstract::The graft status of 14 patients, 13 of whom had received an allogeneic bone marrow transplant (BMT) for severe combined immunodeficiency disease (SCID) and one patient with SCID in whom intrauterine maternal engraftment was suspected, was examined using bone marrow or peripheral blood DNA and a combination of locus-sp...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Katz F,Malcolm S,Strobel S,Finn A,Morgan G,Levinsky R

    更新日期:1990-03-01 00:00:00

  • Predictors of short-term and long-term mortality in critically ill patients admitted to the intensive care unit following allogeneic stem cell transplantation.

    abstract::Historically, the mortality of patients admitted to the ICU after allogeneic stem cell transplantation (alloSCT) is high. Advancements in transplantation procedures, infectious monitoring and supportive care may have improved the outcome. This study aimed to determine short-term and long-term mortality after ICU admis...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/s41409-018-0277-3

    authors: van der Heiden PLJ,Arbous MS,van Beers EJ,van den Bergh WM,le Cessie S,Demandt AMP,Eefting M,Hess C,Kusadasi N,Marijt WAF,van Mook WNKA,Müller MCA,Tuinman PR,van Vliet M,van Westerloo DJ,Blijlevens NMA,HEMA-ICU Study Grou

    更新日期:2019-03-01 00:00:00

  • A phase I trial of recombinant human interleukin-1 beta (OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation.

    abstract::We studied the effects of escalating doses of recombinant human IL-1 beta in patients receiving high-dose chemotherapy and ABMT for metastatic breast cancer or malignant melanoma. Sixteen patients received IL-1 beta, 4 to 32 ng/kg/day administered subcutaneously for 7 days beginning 3 h after bone marrow infusion. Thr...

    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.bmt.1700633

    authors: Elkordy M,Crump M,Vredenburgh JJ,Petros WP,Hussein A,Rubin P,Ross M,Gilbert C,Modlin C,Meisenberg B,Coniglio D,Rabinowitz J,Laughlin M,Kurtzberg J,Peters WP

    更新日期:1997-02-01 00:00:00

  • Outcome of 67 patients with solid tumors relapsed after high-dose chemotherapy and peripheral blood stem cell transplantation.

    abstract::We retrospectively analyzed the outcome of 67 patients with breast (n=24), ovarian (n=11) or testicular cancer (n=32) treated for relapse after high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) transplantation. Treatment, survival and toxicity were analyzed. Patients with breast, ovarian or testicular...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1704047

    authors: Bojko P,Akca A,Seeber S

    更新日期:2003-06-01 00:00:00

  • Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by (18)F-FLT PET scanning.

    abstract::Autologous SCT (auto-SCT) introduces a reduced tolerance to chemotherapy even in patients with adequate engraftment, suggesting long-term effects of the transplantation procedure on the BM capacity. To study the hematopoietic cell compartment after auto-SCT, CD34(+) BM cells (n = 16) from patients at 6-9 months after ...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2010.75

    authors: Woolthuis C,Agool A,Olthof S,Slart RH,Huls G,Smid WM,Schuringa JJ,Vellenga E

    更新日期:2011-01-01 00:00:00

  • Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers.

    abstract::Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixt...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章,多中心研究

    doi:10.1038/bmt.2012.162

    authors: Stern M,Passweg JR,Meyer-Monard S,Esser R,Tonn T,Soerensen J,Paulussen M,Gratwohl A,Klingebiel T,Bader P,Tichelli A,Schwabe D,Koehl U

    更新日期:2013-03-01 00:00:00

  • Clonal cytogenetic changes and myeloma relapse after reduced intensity conditioning allogeneic transplantation.

    abstract::To identify a correlation between metaphase cytogenetics and relapse after reduced intensity conditioning (RIC) allotransplant for patients with multiple myeloma, data on 60 patients (median age 52) who received grafts from a sibling (n = 49) or unrelated donor (n = 11) were analyzed. Fifty-three patients (88%) showed...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1705267

    authors: Lee CK,Zangari M,Fassas A,Thertulien R,Talamo G,Badros A,Cottler-Fox M,van Rhee F,Barlogie B,Tricot G

    更新日期:2006-03-01 00:00:00

  • Long-term donor health and its relationship with outcome of allogeneic hematopoietic stem cell transplantation.

    abstract::Data on long-term follow-up of donors for hematopoietic stem cell transplantation (HSCT) are limited. Donors of 612 adult allogeneic HSCT were studied, at a median of 81 (14-181) months post-HSC donation. Nine donors had severe health problems. Five donors died from aggressive malignancies or terminal illness, at a me...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1705274

    authors: Au WY,Lie AK,Cheng JW,Liang R,Kwong YL

    更新日期:2006-03-01 00:00:00

  • Reduced-intensity rituximab-BEAM-CAMPATH allogeneic haematopoietic stem cell transplantation for follicular lymphoma is feasible and induces durable molecular remissions.

    abstract::The indolent non-Hodgkin's lymphomas are theoretically curable through allogeneic haematopoietic stem cell transplantation (allo-HSCT). The applicability of standard conditioning allo-HSCT is, however, restricted by its toxicity. Recently, reduced-intensity conditioning regimens have demonstrated efficacy with signifi...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1703898

    authors: Ho AY,Devereux S,Mufti GJ,Pagliuca A

    更新日期:2003-04-01 00:00:00

  • Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplant

    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

    authors: Kansagra AJ,Frey NV,Bar M,Laetsch TW,Carpenter PA,Savani BN,Heslop HE,Bollard CM,Komanduri KV,Gastineau DA,Chabannon C,Perales MA,Hudecek M,Aljurf M,Andritsos L,Barrett JA,Bachanova V,Bonini C,Ghobadi A,Gill SI,Hi

    更新日期:2019-11-01 00:00:00

  • Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method.

    abstract::The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine-induced specific immunity in breast cancer patients. Peripheral blood was collected from five breast cancer patients at serial time points in connection with treatment and in a follow...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1703521

    authors: Svane IM,Nikolajsen K,Hansen SW,Kamby C,Nielsen DL,Johnsen HE

    更新日期:2002-04-01 00:00:00

  • Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure.

    abstract::Numerous studies have reported the feasibility and safety of autologous SCT (ASCT) in patients with multiple myeloma (MM) and mild to moderate renal impairment, but there are limited data in dialysis-dependent patients. In this retrospective study, we reviewed the toxicities and efficacy outcomes of 33  MM patients wi...

    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章

    doi:10.1038/bmt.2014.226

    authors: St Bernard R,Chodirker L,Masih-Khan E,Jiang H,Franke N,Kukreti V,Tiedemann R,Trudel S,Reece D,Chen CI

    更新日期:2015-01-01 00:00:00

  • Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency.

    abstract::Genetic mutations of proteins regulating nuclear factor of kappa-light polypeptide gene enhancer in B lymphocyte (NF-kappaB) activation result in heritable diseases of development and immunity. Hypomorphic, X-linked mutations in the IKBKG gene (NF-kappaB essential modulator (NEMO) protein), and hypermorphic, autosomal...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章,多中心研究

    doi:10.1038/bmt.2008.308

    authors: Fish JD,Duerst RE,Gelfand EW,Orange JS,Bunin N

    更新日期:2009-02-01 00:00:00

  • Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.

    abstract::We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105)...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/s41409-020-01007-w

    authors: Gagelmann N,Eikema DJ,de Wreede LC,Rambaldi A,Iacobelli S,Koster L,Caillot D,Blaise D,Remémyi P,Bulabois CE,Passweg J,Leleu X,Zver S,Kobbe G,Ljungman P,Chevallier P,Ringhoffer M,Martin M,Salmenniemi U,Poiré X,Lenh

    更新日期:2021-01-01 00:00:00

  • Comparison of hemorrhagic and ischemic stroke after allogeneic hematopoietic stem cell transplantation.

    abstract::Stroke is an important complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, few studies have been published to analyzed the occurrence and prognosis of stroke after allo-HSCT. From January 2007 to December 2018 in Peking University People's Hospital, 6449 patients receiv...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/s41409-020-0903-8

    authors: Cai X,Fu HX,Mo XD,Wang Y,Zhang YY,Wu J,Han W,Tang FF,Gui RY,Chen H,Chen Y,Zhao P,Yan CH,Wang JZ,Chen YH,Chang YJ,Xu LP,Liu KY,Huang XJ,Zhang XH

    更新日期:2020-11-01 00:00:00

  • Enteral budesonide in treatment for mild and moderate gastrointestinal chronic GVHD.

    abstract::Budesonide (BUD) is a steroid with a low bioavailability, which has been used for the treatment of oral manifestations of chronic GVHD (cGVHD). We retrospectively evaluated the efficacy of BUD in the treatment of gastrointestinal cGVHD. Thirteen patients (median age 47 years) receiving BUD for the treatment of cGVHD a...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2008.209

    authors: Andree H,Hilgendorf I,Leithaeuser M,Junghanss C,Holzhueter S,Loddenkemper C,Steiner B,Freund M,Wolff D

    更新日期:2008-10-01 00:00:00

  • Immune hemolysis involving non-ABO/RhD alloantibodies following hematopoietic stem cell transplantation.

    abstract::We report two cases of severe alloimmune hemolysis after hematopoietic stem cell (HSC) transplant resulting from an anti-Jk(a). The time course of hemolysis and Jk phenotypes of the donor and recipient in the cases reported suggest that the antibody was produced by donor-derived passenger lymphocytes. Retrospective an...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1703074

    authors: Young PP,Goodnough LT,Westervelt P,Diersio JF

    更新日期:2001-06-01 00:00:00

  • Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival.

    abstract::Patients with leukemia relapsing after allogeneic hematopoietic SCT have a dismal prognosis. A second SCT offers a further opportunity for cure, but has a high rate of treatment failure. To determine the utility of this option, we analyzed 59 consecutive patients relapsing after a myeloablative HLA-matched sibling T c...

    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章

    doi:10.1038/bmt.2013.39

    authors: McIver ZA,Yin F,Hughes T,Battiwalla M,Ito S,Koklanaris E,Haggerty J,Hensel NF,Barrett AJ

    更新日期:2013-09-01 00:00:00

  • High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma.

    abstract::To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgki...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Gordon B,Haire W,Kessinger A,Duggan M,Armitage J

    更新日期:1991-12-01 00:00:00

  • Influence of marrow CFU-GM content on engraftment and survival after allogeneic bone marrow transplantation.

    abstract::The influence of the CFU-GM content of donor marrow on the outcome of allogeneic marrow transplantation (BMT) has been debated. We now report 38 patients (25 acute leukemias, 10 chronic myeloid leukemias, two myeloma; 24 in first CR/CP and 14 in more advanced phases of their disease) undergoing unmanipulated HLA-ident...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Bacigalupo A,Piaggio G,Podesta M,Figari O,Benvenuto F,Sogno G,Tedone E,Raffo MR,Grassia L,Ferrero R

    更新日期:1995-02-01 00:00:00

  • Sixty as the new forty: considerations on older related stem cell donors.

    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

    authors: Anderlini P

    更新日期:2017-01-01 00:00:00

  • Randomized comparison of G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells: effects on hematopoietic recovery after high-dose chemotherapy.

    abstract::Fifty patients with either lymphoid or selected solid tumor malignancies were apheresed an identical number of times for PBSC collection after being randomized to receive either G-CSF 10 microg/kg/day alone (arm I), or G-CSF at the same dose with GM-CSF 5 microg/kg/day (arm II). Growth factor(s) was/were given as the ...

    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1038/sj.bmt.1700999

    authors: Spitzer G,Adkins D,Mathews M,Velasquez W,Bowers C,Dunphy F,Kronmueller N,Niemeyer R,McIntyre W,Petruska P

    更新日期:1997-12-01 00:00:00

  • Successful program to prevent aspergillus infections in children undergoing marrow transplantation: use of nasal amphotericin.

    abstract::Aspergillus infections in the pediatric bone marrow transplant (BMT) patients are usually fatal. We began the use of a prophylactic nasal spray of amphotericin in 1990. This nasal spray was provided in addition to low-dose intravenous amphotericin. During the time of this study, the number of fatal cases of aspergillu...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1700618

    authors: Trigg ME,Morgan D,Burns TL,Kook H,Rumelhart SL,Holida MD,Giller RH

    更新日期:1997-01-01 00:00:00

  • Underlying coronary artery disease and successful bone marrow transplantation: a case report.

    abstract::The cardiovascular risk of concurrent coronary artery disease in patients undergoing bone marrow transplantation (BMT) is not well known. We present a case of a 32-year-old male Hodgkin's disease patient with prior chemotherapy and radiotherapy, who underwent autologous BMT. His underlying single vessel coronary arter...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Schechter D,Drakos P,Nagler A

    更新日期:1994-05-01 00:00:00

  • Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients.

    abstract::Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, myelodysplastic syndrome and nonmalignant diseases, who received αβ T- and B-cell-depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and se...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2015.87

    authors: Lang P,Feuchtinger T,Teltschik HM,Schwinger W,Schlegel P,Pfeiffer M,Schumm M,Lang AM,Lang B,Schwarze CP,Ebinger M,Urban C,Handgretinger R

    更新日期:2015-06-01 00:00:00

  • Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation.

    abstract::To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62...

    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1038/bmt.2012.247

    authors: Cesaro S,Pillon M,Tridello G,Aljurf M,Martino R,Schroyens W,Nozzoli C,Barba P,Faraci M,Fagioli F,Cappelli B,Cordonnier C,Al-Mohareb F,Floisand Y,Greil J,Panizzolo IS,Santarone S

    更新日期:2013-06-01 00:00:00

  • Salvage haploidentical transplantation for graft failure using reduced-intensity conditioning.

    abstract::Graft failure is a major concern after cord blood transplantation (CBT) or HLA-haploidentical transplantation (haplo-SCT). As patients who undergo CBT or haplo-SCT almost always lack both matched-related and -unrelated donors, salvage transplantation would also be limited to either CBT or haplo-SCT. In this study, we ...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2011.84

    authors: Yoshihara S,Ikegame K,Taniguchi K,Kaida K,Kim EH,Nakata J,Kato R,Inoue T,Fujioka T,Tamaki H,Okada M,Soma T,Ogawa H

    更新日期:2012-03-01 00:00:00