{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T10:11:42Z","timestamp":1695895902510},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versus-host disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-linked immunosorbent assay (ELISA) method to measure serum levels of total ATLG and evaluate the pharmacokinetics (PK) of the drug in children with \u03b2-Thalassemia, receiving allogeneic HSCT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Diluted serum samples were incubated with Goat-anti-Rabbit IgG antibody coated on a microtiter plate and then, with Goat-anti-Human IgG labeled with horseradish peroxidase. After incubation and washings, substrate solution was added and absorbance was read at 492 nm. ATLG concentrations in samples were determined by interpolation from a standard curve (range: 200\u20130.095 ng\/mL), prepared by diluting a known amount of ATLG in phosphate-buffered saline (PBS). Low, medium, and high-quality control concentrations were 1.56, 6.25, and 25 ng\/mL, respectively. This method was developed and validated within the acceptance criteria in compliance with the Guidelines for a biological method validation: the sensitivity of the method was 0.095 ng\/mL. We analyzed serum samples from 14 children with \u03b2-Thalassemia who received ATLG (Grafalon) at a dose of 10 mg\/kg administered as intravenous (IV) infusion on days \u22125, \u22124, and \u22123 before HSCT (day 0). Blood sampling for PK evaluation was performed on days \u22125, \u22124, and \u22123 before and after drug infusion; and then from day \u22122 to +56.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>The median total ATLG levels pre-IVand post-IV were 0 and 118 mcg\/mL on day \u22125; 85.9 and 199.2 mcg\/mL on day \u22124; 153 and 270.9 mcg\/mL on day \u22123, respectively. The median PK values of CL was 0.0029 (range: 0.0028\u20130.0057) L\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7d<jats:sup>\u22121<\/jats:sup>, V<jats:sub>d<\/jats:sub> was 0.088 (range: 0.025\u20130.448) L\/kg and t<jats:sub>1\/2<\/jats:sub> was 20.2 (range: 5.8\u201350.2) days.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These data suggest that given the marked interindividual variability of total ATLG disposition, the development of a validated ELISA method and the possibility to measure PK parameters in paediatric populations are essential steps to optimize drug therapeutic regimens.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000407","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T15:39:19Z","timestamp":1491925159000},"page":"282-289","source":"Crossref","is-referenced-by-count":0,"title":["A New Enzyme-Linked Immunosorbent Assay for a Total Anti-T Lymphocyte Globulin Determination: Development, Analytical Validation, and Clinical Applications"],"prefix":"10.1097","volume":"39","author":[{"given":"Michela","family":"Montagna","sequence":"first","affiliation":[{"name":"Laboratorio di Farmacocinetica Clinica e Sperimentale, IRCCS Fondazione Policlinico San Matteo, Pavia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"La Nasa","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Centro Trapianti Midollo Osseo, Centro Regionale Trapianti, P. O. \u201cR. Binaghi,\u201d Cagliari;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Immunoematologia Pediatrica, Ospedale San Raffaele, Milano;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Piras","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Centro Trapianti Midollo Osseo, Centro Regionale Trapianti, P. O. \u201cR. Binaghi,\u201d Cagliari;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Avanzini","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia e dei Trapianti, IRCCS Fondazione Policlinico San Matteo, Pavia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Regazzi","sequence":"additional","affiliation":[{"name":"Laboratorio di Farmacocinetica Clinica e Sperimentale, IRCCS Fondazione Policlinico San Matteo, Pavia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Dipartimento Onco\u2013Ematologia Pediatrica e Medicina Trasfusionale, Ospedale Pediatrico Bambino Ges\u00f9, University of Pavia, Roma, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230928","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0889-8588(05)70109-X","article-title":"Bone marrow transplantation for beta-thalassemia","volume":"13","author":"Giardini","year":"1999","journal-title":"Hematol Oncol Clin North Am."},{"key":"R2-20230928","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJM199309163291204","article-title":"Marrow transplantation in patients with thalassemia responsive to iron chelationtherapy","volume":"329","author":"Lucarelli","year":"1993","journal-title":"N Engl J Med."},{"key":"R3-20230928","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1182\/blood.V87.5.2082.2082","article-title":"Marrow transplantation for patients with thalassemia: results in class 3 patients","volume":"87","author":"Lucarelli","year":"1996","journal-title":"Blood"},{"key":"R4-20230928","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/sj.bmt.1701645","article-title":"Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients","volume":"23","author":"Eiermann","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"R5-20230928","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/sj.bmt.1704135","article-title":"Dose-dependent effects of in vitro antithymocyte globulin during conditioning for allogeneic bone marrow transplantation from unrelated donors in patients with chronic phase CML","volume":"32","author":"Scleuning","year":"2003","journal-title":"Bone Marrow Transpl."},{"key":"R6-20230928","first-page":"1910","article-title":"Effect of antithymocyte globulin on quantitative immune recovery and graft-versus-host disease after partially T-cell depleted bone marrow transplantation: a comparison between recipients of matched related and matched unrelated donor grafts","volume":"47","author":"Meijer","year":"2005","journal-title":"Transplantation"},{"key":"R7-20230928","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/01.TP.0000133513.29923.44","article-title":"Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem cell transplantation","volume":"78","author":"Remberger","year":"2004","journal-title":"Transplantation"},{"key":"R8-20230928","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1097\/01.mph.0000184575.00717.25","article-title":"Antithymocyte globulin pharmacokinetics in paediatric patients after haematopoietic stem cell transplantation","volume":"27","author":"Seidel","year":"2005","journal-title":"J Pediatr Hematol Oncol."},{"key":"R9-20230928","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S1470-2045(09)70225-6","article-title":"Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial","volume":"10","author":"Finke","year":"2009","journal-title":"Lancet Oncol."},{"key":"R10-20230928","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1056\/NEJMoa1506002","article-title":"Antilymphocyte globulin for prevention of chronic graft-versus-host disease","volume":"374","author":"Kr\u00f6ger","year":"2016","journal-title":"N Engl J Med."},{"key":"R11-20230928","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.bbmt.2008.05.023","article-title":"Comparison of two doses of antithymocyte globulin in patients undergoing matched unrelated donor allogeneic stem cell transplantation","volume":"14","author":"Ayuk","year":"2008","journal-title":"Biol Blood Marrow Transplant."},{"key":"R12-20230928","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1182\/blood.V128.22.505.505","article-title":"A prospective randomized double blind phase 3 clinical trial of anti-T lymphocyte globulin (ATLG) to assess impact on chronic graft-versus-host disease (cGVHD) free survival in patients undergoing HLA matched unrelated myeloablative hematopoietic cell transplantation (HCT)","volume":"128","author":"Soiffer","year":"2016","journal-title":"Blood"},{"key":"R13-20230928","first-page":"931","article-title":"Rabbit-immunoglobulin G in patients receiving thymoglobulin as a part of conditioning before unrelated donor stem cell transplantation","volume":"90","author":"Remberger","year":"2005","journal-title":"Haematologica"},{"key":"R14-20230928","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s12185-011-0778-y","article-title":"Discrepancy in the kinetics of total and active anti-thymocyte globulin blood concentrations in recipients of allogeneic hematopoietic stem cell transplantation","volume":"93","author":"Yamane","year":"2011","journal-title":"Int J Hematol."},{"key":"R15-20230928","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S2352-3026(15)00045-9","article-title":"Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis","volume":"2","author":"Admiraal","year":"2015","journal-title":"Lancet Haematol."},{"key":"R16-20230928","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s40262-014-0214-6","article-title":"Population pharmacokinetic modeling of thymoglobulin(R) in children receiving allogeneic-hematopoietic cell transplantation: towards improved survival through individualized dosing","volume":"54","author":"Admiraal","year":"2015","journal-title":"Clin Pharmacokinet."},{"key":"R17-20230928","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0966-3274(01)00048-X","article-title":"Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations","volume":"9","author":"Regan","year":"2001","journal-title":"Transpl Immunol."},{"key":"R18-20230928","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S1083-8791(03)00127-7","article-title":"Pharmacokinetics and pharmacodinamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation","volume":"9","author":"Waller","year":"2003","journal-title":"Biol Blood Marrow Transplant."},{"key":"R20-20230928","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","article-title":"Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors","volume":"18","author":"Glucksberg","year":"1974","journal-title":"Transplantation"},{"key":"R21-20230928","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1053\/bbmt.2003.50026","article-title":"Chronic graft-versus-host disease","volume":"9","author":"Lee","year":"2003","journal-title":"Biol Blood Marrow Transpl."},{"key":"R22-20230928","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.bbmt.2009.04.013","article-title":"Low serum levels of total rabbit-IgG is associated with acute graft-versus-host disease after unrelated donor haematopoietic stem cell transplantation: results from a prospective study","volume":"15","author":"Remberger","year":"2009","journal-title":"Biol Blood Marrow Transpl."},{"key":"R23-20230928","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bbmt.2007.12.483","article-title":"Rabbit ATG (thymoglobulin R) pharmacokinetics in pediatric patients receiving a matched unrelated donor bone marrow transplantation. Poster n. 473","volume":"14","author":"Call","year":"2008","journal-title":"Biol Blood Marrow Transplant."},{"key":"R24-20230928","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.bbmt.2008.11.027","article-title":"Total and active rabbit anti-thymocyte (rATG; thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation","volume":"15","author":"Call","year":"2009","journal-title":"Blood Marrow Transplant."},{"key":"R25-20230928","first-page":"29","article-title":"The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man","volume":"45","author":"Bunn","year":"1996","journal-title":"Clin Nephrol."},{"key":"R26-20230928","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.1128\/AAC.06446-11","article-title":"Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children","volume":"9","author":"Robbie","year":"2012","journal-title":"Antimicrob Agents Chemother."},{"key":"R27-20230928","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1034\/j.1399-3046.2002.01086.x","article-title":"Basiliximab in pediatric liver transplantation: a pharmacokinetic-derived dosing algorithm","volume":"6","author":"Kovarik","year":"2002","journal-title":"Pediatr Transplant."},{"key":"R28-20230928","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3109\/10428194.2011.634039","article-title":"Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant","volume":"53","author":"Bashir","year":"2012","journal-title":"Leuk Lymphoma."},{"key":"R29-20230928","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1182\/blood.V98.10.2942","article-title":"Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)","volume":"98","author":"Bacigalupo","year":"2001","journal-title":"Blood"}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201706000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:03:20Z","timestamp":1695863000000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201706000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000407","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}