DOCSLIB.ORG

Steroid-Refractory Acute GVHD: Lack of Long-Term Improved Survival Using New Generation Anticytokine Treatment

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Steroid-Refractory Acute GVHD: Lack of Long-Term Improved Survival Using New Generation Anticytokine Treatment CLINICAL RESEARCH Steroid-Refractory Acute GVHD: Lack of Long-Term Improved Survival Using New Generation Anticytokine Treatment Alienor Xhaard,1 Vanderson Rocha,1,2 Benjamin Bueno,1 Regis Peffault de Latour,1 Julien Lenglet,1 Anna Petropoulou,1 Paula Rodriguez-Otero,1 Patricia Ribaud,1 Raphael Porcher,3 Gerard Socie,1,4 Marie Robin1 There is no consensus on the optimal treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation. In our center, the treatment policy has changed over time with mycophenolate mofetil (MMF) being used from 1999 to 2003, and etanercept or inolimomab after 2004. An observational study compared survival and infection rates in all consecutive patients receiving 1 of these 3 treatments. Ninety-three patients were included. The main end point was over- all survival (OS). Median age was 37 years. Acute GVHD developed at a median of 15 days after transplanta- tion. Second-line treatment was initiated a median of 12 days after aGVHD diagnosis. Therapies were MMF in 56%, inolimomab in 22%, and etanercept in 23% of the patients. Overall, second-line treatment response rate was 45% (complete response: 28%), MMF: 55%, inolimomab: 35%, and etanercept: 28%. With 74 months median follow-up, the 2-year survival was 30% (95% confidence interval: 22-41). Risk factors significantly associated with OS in multivariate analysis were disease status at transplantation; grade III-IV aGVHD at second-line treatment institution; and liver involvement. None of the second-line therapy influenced this poor outcome. Viral and fungal infections were not statistically different among the 3 treatment options; however, bacterial infections were more frequent in patients treated with anticytokines. Over an 11-year period, 3 treatment strategies, including 2 anticytokines, give similar results in patients with SR-aGVHD. Biol Blood Marrow Transplant 18: 406-413 (2012) Ó 2012 American Society for Blood and Marrow Transplantation KEY WORDS: Steroid-refractory graft-versus-host disease, Infection, Anticytokines INTRODUCTION aGVHD (SR-aGVHD) is associated with increased mortality, and the long-term mortality rate remains Acute graft-versus-host disease (aGVHD) is a ma- around 70% [1,2]. jor complication after allogeneic hematopoietic stem First-line treatment of aGVHD is steroids at a dose cell transplantation (alloHSCT). Its frequency varies varying from 1 to 2 mg/kg/day. Response to first-line between 30% and 80% of transplants, depending on steroid therapy is obtained in 40% to 70% of the pa- the type of transplantation. The occurrence of aGVHD tients [3-5]. Consequently, aGVHD remains steroid reportedly decreases relapse of hematologic malignant resistant or refractory in 30% to 60% of the patients. diseases after alloHSCT; however, steroid refractory Numerous second-line treatments have been reported, such as steroid bolus, antithymoglobulin (ATG), my- From the 1Service d’hematologie-greffe, Hopital^ Saint-Louis, cophenolate mofetil (MMF), tacrolimus (FK), siroli- Assistance Publique-Hopitaux^ de Paris, universite Paris 7, Paris, mus, and others. More recently, targeted treatments France; 2Eurocord, Hopital^ Saint-Louis, Paris, France; 3Biosta- against molecules, particularly cytokines implicated tistique et epidemiologie medicale, INSERM U717, Universite in lymphocyte activation, have been used, including 4 Paris 7, Paris, France; and Inserm U728, Universite Paris 7, monoclonal antibodies targeting the anti-interleukin Paris, France. Financial disclosure: See Acknowledgment on page 413. 2 receptor (anti-IL2-R) or anticytokines molecules, Correspondence and reprint requests: Marie Robin, MD, PhD, such as antitumor necrosis factor (anti-TNF) [3,5- Hopital^ Saint-Louis, Assistance Publique-Hopitaux^ de Paris, 15]. Encouraging results have been reported with Universite Paris VII, 1 avenue Claude Vellefaux, 75475 Paris, these agents, with response rates around 50%. Cedex 10, France (e-mail: [email protected]). However, until now, no survival advantage has been Received April 29, 2011; accepted June 24, 2011 Ó 2012 American Society for Blood and Marrow Transplantation demonstrated with any second-line treatment, and no 1083-8791/$36.00 consensus has been reported concerning the optimal doi:10.1016/j.bbmt.2011.06.012 second-line therapy for SR-aGVHD. Systematic 406 Biol Blood Marrow Transplant 18:406-413, 2012 Second-Line Therapy of Steroid-Resistant aGVHD 407 reviews on SR-aGVHD [2] indeed almost invariably were monitored weekly by polymerase chain reaction conclude that 1-year survival still ranges from 30% (PCR) for Epstein-Barr virus (EBV), cytomegalovirus to 40%, that most of the series include few patients, (CMV), adenovirus, and toxoplasmosis. Blood cultures and that follow-up time is usually too short. were performed daily during hospitalization, and se- With this in mind, we here report data on nearly rum galactomannan dosage was performed twice a 100 patients with long-term follow-up. In our center, week. Preemptive treatment strategies were used for the policy to treat SR-aGVHD has changed CMV and EBV reactivations. For bacterial infections, over time. From 1999 to 2003, MMF was regularly only sepsis, pneumonia, and documented infections used, whereas, after 2004, inolimomab (anti-IL2-R) or were taken into account. For viral infections, respira- etanercept (anti-TNF) were used: inolimomab was tory viral infection, CMV, EBV, adenoviral infection, preferentially used in patients with primarily skin disseminated herpes infection, HHV6 encephalitis, involvement and etanercept in patients with primarily and varicella/zona (VZV) were taken into account. All gut or liver involvement. We conducted a retrospective data were collected from the PROMISE database and study to compare response rates and infection incidents the patients’ charts, which are prospectively filled. All after these second-line therapies and looked for im- patients gave their consent for data collection before proved overall survival (OS), if any, in patients with transplantation. a first episode of SR-aGVHD. Statistics MATERIALS AND METHODS The main endpoint was OS in each treatment group. Secondary endpoints were response to treat- Data, Definition, and Procedures ment, infection rates, relapse rates, and mean treatment Patients included in this study received an allo- cost. Response to treatment was judged into 4 cate- HSCT at Saint-Louis Hospital, Paris, France. Children gories. Complete response (CR) was defined as the above 4 years of age and adults were included. All disappearance of any GVHD signs from all organs consecutive patients who received these second-line involved during at least 1 month. Stable disease (SD) therapies for SR-aGVHD were included from 1999 was considered when the grading of GVHD in all or- to 2010. All patients continued to receive a calcineurine gans was identical after treatment compared with time inhibitor (CNI) in addition to second-line treatment. of treatment initiation. Progressive disease (PD) corre- Some patients treated by MMF received tacrolimus sponded to worsening of GVHD grading in at least (FK), others received cyclosporine A (CsA), Because 1 organ. Other patients were considered to have partial no difference in patients’ characteristics and survival response (PR). Factors associated with CR were ana- was noticeable with either CsA or FK (data not shown), lyzed using logistic regression models. Cumulative inci- patients were grouped into a single treatment, that is, dence of CR and infections after second-line treatment CNI and MMF. Patients who received a GVHD pro- were estimated using the usual methodology [18].For phylaxis by MMF could not be included in the second- CR, progression and death were considered as compet- line therapy group MMF. Ninety-three patients met ing events, and patients receiving a third-line treatment the inclusion criteria. Acute GVHD was defined ac- with no evidence of progression (ie, while in PR or SD) cording to modified Glucksberg’s criteria [16,17]. All were censored at the time of third-line treatment initi- patients were treated with corticosteroids (2 mg/kg/ ation. When comparing survival according to CR, sur- day) as first-line treatment. SR-aGVHD was defined vival of patients achieving CR was counted from the as a progressive disease after 3 days of treatment, stable time of first evidence of CR, whereas survival of patients disease at 7 days of treatment, or partial response at 14 who did not achieve CR was counted from the date of days. After the beginning of the second-line treatment, initiation of second-line treatment. Survival of patients steroids were initially continued at the same dosage for who received a third-line treatment with no evidence of a minimal duration of 14 days and slowly tapered over progression was censored at that time. Viral, bacterial, time; CNI were continued. Disease staging and grad- and fungal infections were analyzed separately, with ing were prospectively evaluated at regular intervals death being considered as a competing event. The asso- (day 13, 17, and 114). Etanercept was given subcuta- ciation between second-line treatment and infection neously at 25 mg per dose twice a week for 4 weeks and was analyzed using Cox proportional cause-specific then pursued at 25 mg once a week for another 4 hazards model [19]. To model recurrence of weeks. Inolimomab was given intravenously at 0.3 infectious episodes, the Anderson-Gill approach was mg/kg/day for 8 days, then at 0.4 mg/kg 3 times
Load more

Recommended publications
  • Fig. L COMPOSITIONS and METHODS to INHIBIT STEM CELL and PROGENITOR CELL BINDING to LYMPHOID TISSUE and for REGENERATING GERMINAL CENTERS in LYMPHATIC TISSUES
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date Χ 23 February 2012 (23.02.2012) WO 2U12/U24519ft ft A2 (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/US201 1/048297 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 18 August 201 1 (18.08.201 1) NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/374,943 18 August 2010 (18.08.2010) US kind of regional protection available): ARIPO (BW, GH, 61/441,485 10 February 201 1 (10.02.201 1) US GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, 61/449,372 4 March 201 1 (04.03.201 1) US ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (72) Inventor; and EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (71) Applicant : DEISHER, Theresa [US/US]; 1420 Fifth LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Avenue, Seattle, WA 98101 (US).
    [Show full text]
  • Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients
    antibodies Review Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients Andrew T. Lucas 1,2,3,*, Ryan Robinson 3, Allison N. Schorzman 2, Joseph A. Piscitelli 1, Juan F. Razo 1 and William C. Zamboni 1,2,3 1 University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA; [email protected] (J.A.P.); [email protected] (J.F.R.); [email protected] (W.C.Z.) 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-919-966-5242; Fax: +1-919-966-5863 Received: 30 November 2018; Accepted: 22 December 2018; Published: 1 January 2019 Abstract: The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution.
    [Show full text]
  • Interleukins in Therapeutics
    67 ISSN: 2347 - 7881 Review Article Interleukins in Therapeutics Anjan Khadka Department of Pharmacology, AFMC, Pune, India [email protected] ABSTRACT Interleukins are a subset of a larger group of cellular messenger molecules called cytokines, which are modulators of cellular behaviour. On the basis of their respective cytokine profiles, responses to chemokines, and interactions with other cells, these T-cell subsets can promote different types of inflammatory responses. During the development of allergic disease, effector TH2 cells produce IL-4, IL- 5, IL-9, and IL-32. IL-25, IL- 31, and IL-33 contributes to TH2 responses and inflammation. These cytokines have roles in production of allergen-specific IgE, eosinophilia, and mucus. ILs have role in therapeutics as well as diagnosis and prognosis as biomarker in various conditions. Therapeutic targeting of the IL considered to be rational treatment strategy and promising biologic therapy. Keywords: Interleukins, cytokines, Interleukin Inhibitors, Advances INTRODUCTION meaning ‘hormones’. It was Stanley Cohen in Interleukins are group of cytokines that were 1974 who for the first time introduced the term first seen to be expressed by leucocytes and ‘‘cytokine’’. It includes lymphokines, they interact between cells of the immune monokines, interleukins, and colony stimulating systems. It is termed by Dr. Vern Paetkau factors (CSFs), interferons (IFNs), tumor (University of Victoria) in1979.Interleukins (IL) necrosis factor (TNF) and chemokines. The are able to promote cell growth, differentiation, majority of interleukins are synthesized by and functional activation. The question of how helper CD4 T lymphocytes as well as through diverse cell types communicate with each monocytes, macrophages, and endothelial cells.
    [Show full text]
  • Challenges and Approaches for the Development of Safer Immunomodulatory Biologics
    REVIEWS Challenges and approaches for the development of safer immunomodulatory biologics Jean G. Sathish1*, Swaminathan Sethu1*, Marie-Christine Bielsky2, Lolke de Haan3, Neil S. French1, Karthik Govindappa1, James Green4, Christopher E. M. Griffiths5, Stephen Holgate6, David Jones2, Ian Kimber7, Jonathan Moggs8, Dean J. Naisbitt1, Munir Pirmohamed1, Gabriele Reichmann9, Jennifer Sims10, Meena Subramanyam11, Marque D. Todd12, Jan Willem Van Der Laan13, Richard J. Weaver14 and B. Kevin Park1 Abstract | Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions — including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity — pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. Immunomodulatory Biologics currently represent more than 30% of licensed The high specificity of the interactions of immu- biologics pharmaceutical products and have expanded the thera- nomodulatory biologics with their relevant immune Biotechnology-derived peutic options available
    [Show full text]
  • Anticorps FR-EN 110X90.Indd
    MONOCLONAL ANTIBODIES and Fc fusion proteins for therapeutic use DISTRIBUTION OF INTERNATIONAL NONPROPRIETARY NAMES BY INDICATION SOLID TUMORS RHUMATOLOGY PNEUMOLOGY Lung cancer bevacizumab Rheumatoid arthritis etanercept Allergic asthma omalizumab nivolumab infliximab Severe eosinophilic asthma mepolizumab necitumumab adalimumab reslizumab atezolizumab rituximab Colorectal cancer bevacizumab abatacept TRANSPLANTATION cetuximab tocilizumab Transplant rejection basiliximab panitumumab certolizumab pegol belatacept aflibercept golimumab Graft versus host disease inolimomab Bladder cancer atezolizumab Psoriatic arthritis etanercept Breast cancer trastuzumab adalimumab OPHTALMOLOGY bevacizumab infliximab Age related macular ranibizumab pertuzumab golimumab degeneration aflibercept trastuzumab entansine ustekinumab bevacizumab Gastric cancer trastuzumab certolizumab pegol Macular edema ranibizumab ramucirumab secukinumab aflibercept Head and neck cancer cetuximab Ankylosing spondylitis infliximab Myopic choroidal ranibizumab Ovarian cancer bevacizumab etanercept neovascularization aflibercept Fallopian tube cancer bevacizumab adalimumab Cervical cancer bevacizumab golimumab HAEMOSTASIS AND THROMBOSIS Kidney cancer bevacizumab certolizumab pegol nivolumab secukinumab Haemophilia A efmoroctocog α Melanoma ipilimumab Juvenile arthritis etanercept Haemophilia B eftrenonacog α nivolumab adalimumab Reversal of dabigatran idarucizumab Idiopathic thrombocytopenic pembrolizumab abatacept romiplostim Neuroblastoma dinutuximab tocilizumab purpura Malignant
    [Show full text]
  • Simulect® (Basiliximab)
    UnitedHealthcare® Value & Balance Exchange Medical Benefit Drug Policy Simulect® (Basiliximab) Policy Number: IEXD0219.02 Effective Date: July 1, 2021 Instructions for Use Table of Contents Page Related Policies Applicable States ........................................................................... 1 None Coverage Rationale ....................................................................... 1 Applicable Codes .......................................................................... 1 Background.................................................................................... 2 Clinical Evidence ........................................................................... 2 U.S. Food and Drug Administration ............................................. 2 References ..................................................................................... 2 Policy History/Revision Information ............................................. 2 Instructions for Use ....................................................................... 3 Applicable States This Medical Benefit Drug Policy only applies to the states of Arizona, Maryland, North Carolina, Oklahoma, Tennessee, Virginia, and Washington. Coverage Rationale Simulect is proven and medically necessary for the treatment of prophylaxis of acute organ rejection when all of the following criteria are met: Patient has received a kidney transplant; and Physician provided documentation that patient’s prophylaxis therapy includes cyclosporine modified and corticosteroids; and Simulect
    [Show full text]
  • As Treatment for Refractory Acute Graft-Versus-Host Disease
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Biology of Blood and Marrow Transplantation 12:1135-1141 (2006) provided by Elsevier - Publisher Connector ᮊ 2006 American Society for Blood and Marrow Transplantation 1083-8791/06/1211-0001$32.00/0 doi:10.1016/j.bbmt.2006.06.010 Encouraging Results with Inolimomab (Anti-IL-2 Receptor) as Treatment for Refractory Acute Graft-versus-Host Disease Jose Luis Piñana, David Valcárcel, Rodrigo Martino, M. Estela Moreno, Anna Sureda, Javier Briones, Salut Brunet, Jorge Sierra Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain Correspondence and reprint requests: David Valcárcel, Division of clinical Hematology, Hospital de la Santa Creu i Sant Pau, St Antoni Ma Claret 167, Barcelona 08021, Spain (e-Mail: [email protected]). Received September 16, 2005; accepted June 21, 2006 ABSTRACT Enlimomab, an anti-interleukin-2 receptor (anti-IL-2R) monoclonal antibody, may be useful in the treatment of steroid-refractory acute graft-versus-host disease (aGVHD) by inhibiting 1 of its putative immunopatho- genic pathways. We retrospectively analyzed 40 consecutive patients who received enlimomab as salvage treatment for steroid refractory aGVHD at a single institution between June 1999 and December 2004. Enlimomab was given intravenously at a dose of 11 mg/d for 3 consecutive days, followed by 5.5 mg/d for 7 consecutive days and then 5.5 mg every other day for 5 doses. No infusion-related side effects were noted. Twenty-three patients (58%) responded, including 15 (38%) complete and 8 (20%) partial responses.
    [Show full text]
  • Downloaded Here
    Antibodies to Watch in a Pandemic Dr. Janice M. Reichert, Executive Director, The Antibody Society August 27, 2020 (updated slides) Agenda • US or EU approvals in 2020 • Granted as of late July 2020 • Anticipated by the end of 2020 • Overview of antibody-based COVID-19 interventions in development • Repurposed antibody-based therapeutics that treat symptoms • Newly developed anti-SARS-CoV-2 antibodies • Q&A 2 Number of first approvals for mAbs 10 12 14 16 18 20 Annual first approvals in either the US or EU or US the either in approvals first Annual 0 2 4 6 8 *Estimate based on the number actually approved and those in review as of July 15, with assumption of approval on the first c first the on of approval assumption 15, with as July of review in those and approved actually number the on based *Estimate Tables of approved mAbs and antibodies in review available at at mAbs ofand available in antibodies approved review Tables 1997 98 99 2000 01 02 03 Year of first US or EU approval or EU US of first Year 04 05 06 https://www.antibodysociety.org/resources/approved 07 08 09 10 11 12 13 14 15 Non-cancer Cancer 16 - antibodies/ 17 ycl 18 e. 19 2020* First approvals US or EU in 2020 • Teprotumumab (Tepezza): anti-IGF-1R mAb for thyroid eye disease • FDA approved on January 21 • Eptinezumab (Vyepti): anti-CGRP IgG1 for migraine prevention • FDA approved on February 21 • Isatuximab (Sarclisa): anti-CD38 IgG1 for multiple myeloma • FDA approved on March 2, also approved in the EU on June 2 • Sacituzumab govitecan (Trodelvy): anti-TROP-2 ADC for triple-neg.
    [Show full text]
  • September 2017 ~ Resource #330909
    −This Clinical Resource gives subscribers additional insight related to the Recommendations published in− September 2017 ~ Resource #330909 Medications Stored in the Refrigerator (Information below comes from current U.S. and Canadian product labeling and is current as of date of publication) Proper medication storage is important to ensure medication shelf life until the manufacturer expiration date and to reduce waste. Many meds are recommended to be stored at controlled-room temperature. However, several meds require storage in the refrigerator or freezer to ensure stability. See our toolbox, Medication Storage: Maintaining the Cold Chain, for helpful storage tips and other resources. Though most meds requiring storage at temperatures colder than room temperature should be stored in the refrigerator, expect to see a few meds require storage in the freezer. Some examples of medications requiring frozen storage conditions include: anthrax immune globulin (Anthrasil [U.S. only]), carmustine wafer (Gliadel [U.S. only]), cholera (live) vaccine (Vaxchora), dinoprostone vaginal insert (Cervidil), dinoprostone vaginal suppository (Prostin E2 [U.S.]), varicella vaccine (Varivax [U.S.]; Varivax III [Canada] can be stored in the refrigerator or freezer), zoster vaccine (Zostavax [U.S.]; Zostavax II [Canada] can be stored in the refrigerator or freezer). Use the list below to help identify medications requiring refrigerator storage and become familiar with acceptable temperature excursions from recommended storage conditions. Abbreviations: RT = room temperature Abaloparatide (Tymlos [U.S.]) Aflibercept (Eylea) Amphotericin B (Abelcet, Fungizone) • Once open, may store at RT (68°F to 77°F • May store at RT (77°F [25°C]) for up to Anakinra (Kineret) [20°C to 25°C]) for up to 30 days.
    [Show full text]
  • B Cell Immunity in Solid Organ Transplantation
    REVIEW published: 10 January 2017 doi: 10.3389/fimmu.2016.00686 B Cell Immunity in Solid Organ Transplantation Gonca E. Karahan, Frans H. J. Claas and Sebastiaan Heidt* Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands The contribution of B cells to alloimmune responses is gradually being understood in more detail. We now know that B cells can perpetuate alloimmune responses in multiple ways: (i) differentiation into antibody-producing plasma cells; (ii) sustaining long-term humoral immune memory; (iii) serving as antigen-presenting cells; (iv) organizing the formation of tertiary lymphoid organs; and (v) secreting pro- as well as anti-inflammatory cytokines. The cross-talk between B cells and T cells in the course of immune responses forms the basis of these diverse functions. In the setting of organ transplantation, focus has gradually shifted from T cells to B cells, with an increased notion that B cells are more than mere precursors of antibody-producing plasma cells. In this review, we discuss the various roles of B cells in the generation of alloimmune responses beyond antibody production, as well as possibilities to specifically interfere with B cell activation. Keywords: HLA, donor-specific antibodies, antigen presentation, cognate T–B interactions, memory B cells, rejection Edited by: Narinder K. Mehra, INTRODUCTION All India Institute of Medical Sciences, India In the setting of organ transplantation, B cells are primarily known for their ability to differentiate Reviewed by: into long-lived plasma cells producing high affinity, class-switched alloantibodies. The detrimental Anat R. Tambur, role of pre-existing donor-reactive antibodies at time of transplantation was already described in Northwestern University, USA the 60s of the previous century in the form of hyperacute rejection (1).
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • Stem Cell Donor Is a Costful and Timely Procedure
    P509 to 8 of 10 possible MM occurred: No MM (4%), 1 MM (10%), 2 Cord Blood Bank of the Czech Republic, six month check MM (15%), 3 MM (22%), 4 MM (25%), 5 MM (12%), 6 MM I. Fales, S. Rahmatova, P. Kobylka, S. Matejckova, L. (6%), 7 MM (3%), 8 MM (2%). There was no significant Zahlavova, A. Hruba Institute of Hematology and Blood association between the number of MM (also analysed in Transfusion (Prague, CZ) GvHD or rejection direction) using HR-level for both HLA-A, -B and -DRB1 and HLA-A, B, C, DRB1 and DQB1 and the Cord Blood Bank of the Czech Republic (CCB CR) was incidence of aGvHD grade II-IV. There was a trend that MM in established in the year 1996. But the first collection of the cord class I HR were associated with neutrophil recovery; HLA-A blood (for the related part) in this project was performed in locus typing analysed in rejection direction as well as 1 or 2 A- 1994. It was planned collection for sibling suffering with LAD locus HLA disparities were associated with reduced CI of syndrome. The transplantation of the fully matched graft was engraftment (p= 0.04). The same was observed for the HLA- performed in the same year and it was first transplantation of C-KIR epitopes in rejection (HvG) direction (p=0.01). No the patient with this diagnosis by cord blood on the world. significant correlation was found between numbers of HLA- Actually 3 processing and 28 collection centres are MM on HR level with 2-year survival.
    [Show full text]