Population Pharmacokinetic Modeling of Thymoglobulin® in Children Receiving Allogeneic-Hematopoietic Cell Transplantation: Towards Improved Survival Through Individualized Dosing

Clinical Pharmacokinetics

Volumn 54, Issue 4, 2015, Pages 435-446

  Admiraal, Rick ^a,b,c   van Kesteren, Charlotte ^a,b   Jol van der Zijde, Cornelia M ^c   van Tol, Maarten J D ^c   Bartelink, Imke H ^a,d   Bredius, Robbert G M ^c   Boelens, Jaap Jan ^a   Knibbe, Catherijne A J ^b,e  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b LEIDEN UNIVERSITY   (Netherlands)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^d UNIVERSITY OF SAN FRANCISCO   (United States)

^e ST ANTONIUS HOSPITAL   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

THYMOCYTE ANTIBODY; IMMUNOSUPPRESSIVE AGENT; LYMPHOCYTE ANTIBODY;

ADOLESCENT; ADULT; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ARTICLE; BODY SIZE; BODY WEIGHT; CENTRAL VOLUME OF DISTRIBUTION; COHORT ANALYSIS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONCENTRATION; FEMALE; HUMAN; INFANT; LIMIT OF QUANTITATION; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MICHAELIS CONSTANT; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; ALGORITHM; BLOOD; CHILD; DRUG ADMINISTRATION; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; METABOLISM; PRESCHOOL CHILD; PROCEDURES; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; ALGORITHMS; ANTILYMPHOCYTE SERUM; CHILD; CHILD, PRESCHOOL; DRUG ADMINISTRATION SCHEDULE; FEMALE; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFANT; LYMPHOCYTE COUNT; MALE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84925536326     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-014-0214-6     Document Type: Article

References (44)

1. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino P, di Bartolomeo P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001; 98:2942–7. http://www.bloodjournal.org/cgi/doi/10.1182/blood.V98.10.2942. Accessed 28 Aug 2013.
2. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. 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. Lancet Oncol. 2009;10:855–64.
3. Byrne JL, Stainer C, Cull G, Haynes AP, Bessell EM, Hale G, et al. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transpl. 2000;25:411–7.
4. Pihusch R, Holler E, Mühlbayer D, Göhring P, Stötzer O, Pihusch M, et al. The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation. Bone Marrow Transpl. 2002;30:347–54.
5. Theurich S, Fischmann H, Chemnitz J, Holtick U, Scheid C, Skoetz N. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst Rev. 2012;9:CD009159.
6. Lindemans CA, Chiesa R, Amrolia PJ, Rao K, Nikolajeva O, de Wildt A, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood. 2014;123:126–32.
7. Szabolcs P, Niedzwiecki D. Immune reconstitution after unrelated cord blood transplantation. Cytotherapy. 2007;9:111–22.
8. Jacobson CA, Turki A, McDonough S, Stevenson KE, Kim HT, Kao G, et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transpl. 2012;18:565–74.
9. Thomas-Vaslin V, Altes HK, De Boer RJ, Klatzmann D. Comprehensive assessment and mathematical modeling of T-cell population dynamics and homeostasis. J Immunol. 2008;180:2240–50.
10. Williams K, Hakim FT, Gress RE. T-cell immune reconstitution following lymphodepletion. Semin Immunol. 2008;19:318–30.
11. Krenger W, Blazar BR, Holländer GA. Thymic T-cell development in allogeneic stem cell transplantation. Blood. 2011;117:6768–76. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3128475&tool=pmcentrez&rendertype=abstract. Accessed 12 Aug 2013.
12. Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel LM, Podgorny P, et al. Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Cytotherapy. 2012;14:1258–75.
13. Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJJ, Zhan H, et al. Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012;156:656–66.
14. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DW, Leeder JS, Kauffman RE. Developmental pharmacology—drug disposition, action and therapy in infants and children. N Engl J Med. 2003;349:1157–67.
15. Admiraal R, van Kesteren C, Boelens JJ, Bredius RGM, Tibboel D, Knibbe CA. Towards evidence-based dosing regimens in children on the basis of population pharmacokinetic pharmacodynamic modelling. Arch Dis Child. 2014;99:267–72.
16. De Cock RFW, Piana C, Krekels EHJ, Danhof M, Allegaert K, Knibbe CA. The role of population PK-PD modelling in paediatric clinical research. Eur J Clin Pharmacol. 2011;67(Suppl 1):5–16.
17. Knibbe CAJ, Krekels EHJ, Danhof M. Advances in paediatric pharmacokinetics. Expert Opin Drug Metab Toxicol. 2011;7:1–8.
18. Bartelink IH, van Kesteren C, Boelens JJ, Egberts TCG, Bierings MB, Cuvelier GDE, et al. Predictive performance of a busulfan pharmacokinetic model in children and young adults. Ther Drug Monit. 2012;34:574–83.
19. Bartelink IH, van Reij EML, Gerhardt CE, van Maarseveen EM, de Wildt A, Versluys B, et al. Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transpl. 2013;20:1–9.
20. Waller EK, Langston AA, Lonial S, Cherry J, Somani J, Allen AJ, et al. Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation. Biol Blood Marrow Transpl. 2003;9:460–71. http://linkinghub.elsevier.com/retrieve/pii/S1083879103001277. Accessed 29 Aug 2013.
21. Seidel MG, Fritsch G, Matthes-Martin S, Lawitschka A, Lion T, Po U, et al. Antithymocyte globulin pharmacokinetics in pediatric patients after hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2005;27:532–6.
22. Remberger M, Persson M, Mattsson J, Gustafsson B, Uhlin M. Effects of different serum-levels of ATG after unrelated donor umbilical cord blood transplantation. Transpl Immunol. 2012;27:59–62.
23. Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N. Heterogeneous clearance of antithymocyte globulin after CD34+-selected allogeneic hematopoietic progenitor cell transplantation. Biol Blood Marrow Transpl. 2005;11:609–18.
24. Bashir Q, Munsell MF, Giralt S, de Padua Silva L, Sharma M, Couriel D, et al. Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant. Leuk Lymphoma. 2012;53:915–9.
25. Jol-van der Zijde C, Bredius R, Jansen-Hoogendijk A, Raaijmakers S, Egeler R, Lankester A, et al. IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD. Bone Marrow Transpl. 2012;47:360–8.
26. Call SK, Kasow KA, Barfield R, Madden R, Leung W, Horwitz E, et al. Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation. Biol Blood Marrow Transpl. 2009;15:274–8.
27. Regan JF, Lyonnais C, Campbell K, Van Smith L. Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations. Transpl Immunol. 2001;9:29–36.
28. Rebello P, Hale G. Pharmacokinetics of CAMPATH-1H: assay development and validation. J Immunol Methods. 2002;260:285–302.
29. Bauer RJ. NONMEM users guide: introduction to NONMEM 7.2.0. Ellicott City: ICON Development Solutions; 2011. p. 1–131.
30. Keizer RJ, van Benten M, Beijnen JH, Schellens JHM, Huitema ADR. Piraña and PCluster: a modeling environment and cluster infrastructure for NONMEM. Comput Methods Progr Biomed. 2011;101:72–9.
31. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2008.
32. Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28:481–504.
33. Krekels EHJ, Neely M, Panoilia E, Tibboel D, Capparelli E, Danhof M, et al. From pediatric covariate model to semiphysiological function for maturation: part I-extrapolation of a covariate model from morphine to Zidovudine. CPT Pharmacometrics Syst Pharmacol. 2012;1:e9.
34. Krekels EHJ, Johnson TN, den Hoedt SM, Rostami-Hodjegan A, Danhof M, Tibboel D, et al. From pediatric covariate model to semiphysiological function for maturation: part II-sensitivity to physiological and physicochemical properties. CPT Pharmacometrics Syst Pharmacol. 2012;1:e10.
35. Krekels EHJ, van Hasselt JGC, Tibboel D, Danhof M, Knibbe CA. Systematic evaluation of the descriptive and predictive performance of paediatric morphine population models. Pharm Res. 2011;28:797–811.
36. Lindbom L, Pihlgren P, Jonsson EN, Jonsson N. PsN-Toolkit–a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Progr Biomed. 2005;79:241–57.
37. Comets E, Brendel K, Mentré F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Progr Biomed. 2008;90:154–66.
38. Gibiansky L, Gibiansky E, Kakkar T, Ma P. Approximations of the target-mediated drug disposition model and identifiability of model parameters. J Pharmacokinet Pharmacodyn. 2008;35:573–91.
39. Yan X, Mager DE, Krzyzanski W. Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models. J Pharmacokinet Pharmacodyn. 2010;37:25–47. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3157300&tool=pmcentrez&rendertype=abstract. Accessed 16 Mar 2014.
40. Mould DR, Baumann A, Kuhlmann J, Keating MJ, Weitman S, Hillmen P, et al. Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukaemia and its link to treatment response. Br J Clin Pharmacol. 2007;64:278–91.
41. Feng X, Scheinberg P, Biancotto A, Rios O, Donaldson S, Wu C, et al. In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. Haematologica. 2014;99:1433–40
42. Knibbe CAJ, Danhof M. Individualized dosing regimens in children based on population PKPD modelling: are we ready for it? Int J Pharm. 2011;415:9–14.
43. Remberger M, Svahn B, Mattsson J, Ringden O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004;78:122–7.
44. Remberger M, Ringdén O, Hägglund H, Svahn B-M, Ljungman P, Uhlin M, et al. A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors. Clin Transpl. 2013;27:E368–74.