Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II

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• 作者：Jeannine S. McCune ; Meagan J. Bemer ; Janel Long-Boyle
• 刊名：Clinical Pharmacokinetics
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：55
• 期：5
• 页码：551-593
• 全文大小：1,063 KB
• 参考文献：1.Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997;89:3048–54.PubMed
  2.Yu C, Seidel K, Nash RA, et al. Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. Blood. 1998;91:2581–7.PubMed
  3.McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–400.PubMed CrossRef
  4.Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101:1620–9.PubMed CrossRef
  5.Bolwell B, Sobecks R, Pohlman B, et al. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004;34:621–5.PubMed CrossRef
  6.Neumann F, Graef T, Tapprich C, et al. Cyclosporine A and mycophenolate mofetil vs cyclosporine A and methotrexate for graft-versus-host disease prophylaxis after stem cell transplantation from HLA-identical siblings. Bone Marrow Transplant. 2005;35:1089–93.PubMed CrossRef
  7.Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102:2021–30.PubMed CrossRef
  8.Tomblyn M, Brunstein C, Burns LJ, et al. Similar and promising outcomes in lymphoma patients treated with myeloablative or nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2008;14:538–45.PubMed PubMedCentral CrossRef
  9.Brunstein CG, Barker JN, Weisdorf DJ, et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplant outcomes in 110 adults with hematological disease. Blood. 2007;110:3064–70.PubMed PubMedCentral CrossRef
  10.Giaccone L, McCune JS, Maris MB, et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood. 2005;106:4381–8.PubMed PubMedCentral CrossRef
  11.Jacobson P, Rogosheske J, Barker JN, et al. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther. 2005;78:486–500.PubMed CrossRef
  12.Royer B, Larosa F, Legrand F, et al. Pharmacokinetics of mycophenolic acid administered 3 times daily after hematopoietic stem cell transplantation with reduced-intensity regimen. Biol Blood Marrow Transplant. 2009;15:1134–9.PubMed CrossRef
  13.Haentzschel I, Freiberg-Richter J, Platzbecker U, et al. Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Bone Marrow Transplant. 2008;42:113–20.PubMed CrossRef
  14.Bhatia M, Militano O, Jin Z, et al. An age-dependent pharmacokinetic study of intravenous and oral mycophenolate mofetil in combination with tacrolimus for GVHD prophylaxis in pediatric allogeneic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2010;16:333–43.PubMed CrossRef
  15.Jacobson P, El-Massah SF, Rogosheske J, et al. Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation. Bone Marrow Transplant. 2009;44:113–20.PubMed PubMedCentral CrossRef
  16.Jacobson P, Green K, Rogosheske J, et al. Highly variable mycophenolate mofetil bioavailability following nonmyeloablative hematopoietic cell transplantation. J Clin Pharmacol. 2007;47:6–12.PubMed CrossRef
  17.Jacobson P, Huang J, Rydholm N, et al. Higher mycophenolate dose requirements in children undergoing hematopoietic cell transplant (HCT). J Clin Pharmacol. 2008;48:485–94.PubMed CrossRef
  18.Jacobson P, Long J, Rogosheske J, Brunstein C, Weisdorf D. High unbound mycophenolic acid concentrations in a hematopoietic cell transplantation patient with sepsis and renal and hepatic dysfunction. Biol Blood Marrow Transplant. 2005;11:977–8.PubMed CrossRef
  19.Jenke A, Renner U, Richte M, et al. Pharmacokinetics of intravenous mycophenolate mofetil after allogeneic blood stem cell transplantation. Clin Transplant. 2001;15:176–84.PubMed CrossRef
  20.Nash RA, Johnston L, Parker P, et al. A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005;11:495–505.PubMed CrossRef
  21.van Hest RM, Doorduijn JK, de Winter BC, et al. Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients. Ther Drug Monit. 2007;29:353–60.PubMed CrossRef
  22.Osunkwo I, Bessmertny O, Harrison L, et al. A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients. Biol Blood Marrow Transplant. 2004;10:246–58.PubMed CrossRef
  23.Bornhauser M, Schuler U, Porksen G, et al. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation. 1999;67:499–504.PubMed CrossRef
  24.Wakahashi K, Yamamori M, Minagawa K, et al. Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation. Int J Hematol. 2011;94:193–202.PubMed CrossRef
  25.de Winter BC, Mathot RA, Sombogaard F, et al. Differences in clearance of mycophenolic acid among renal transplant recipients, hematopoietic stem cell transplant recipients, and patients with autoimmune disease. Ther Drug Monit. 2010;32:606–14.PubMed CrossRef
  26.Frymoyer A, Verotta D, Jacobson P, Long-Boyle J. Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors. Br J Clin Pharmacol. 2013;75:463–75.PubMed PubMedCentral CrossRef
  27.Li H, Mager DE, Bemer MJ, et al. A limited sampling schedule to estimate mycophenolic acid area under the concentration-time curve in hematopoietic cell transplantation recipients. J Clin Pharmacol. 2012;52:1654–64.PubMed PubMedCentral CrossRef
  28.Saint-Marcoux F, Royer B, Debord J, et al. Pharmacokinetic modelling and development of Bayesian estimators for therapeutic drug monitoring of mycophenolate mofetil in reduced-intensity haematopoietic stem cell transplantation. Clin Pharmacokinet. 2009;48:667–75.PubMed PubMedCentral CrossRef
  29.Kim H, Long-Boyle J, Rydholm N, et al. Population pharmacokinetics of unbound mycophenolic acid in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplantation. J Clin Pharmacol. 2012;52:1665–75.PubMed CrossRef
  30.Li H, Mager DE, Sandmaier BM, Maloney DG, Bemer MJ, McCune JS. Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil. J Clin Pharmacol. 2013;53:393–402.PubMed PubMedCentral CrossRef
  31.Li H, Mager DE, Sandmaier BM, et al. Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate dehydrogenase activity in hematopoietic cell transplantation recipients treated with mycophenolate mofetil. Biol Blood Marrow Transplant. 2014;20:1121–9.PubMed PubMedCentral CrossRef
  32.Weber LT, Shipkova M, Armstrong VW, et al. Comparison of the Emit immunoassay with HPLC for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem. 2002;48:517–25.PubMed
  33.Martiny D, Macours P, Cotton F, Thiry P, Gulbis B. Reliability of mycophenolic acid monitoring by an enzyme multiplied immunoassay technique. Clin Lab. 2010;56:345–53.PubMed
  34.Rebollo N, Calvo MV, Martin-Suarez A, Dominguez-Gil A. Modification of the EMIT immunoassay for the measurement of unbound mycophenolic acid in plasma. Clin Biochem. 2011;44:260–3.PubMed CrossRef
  35.Chen B, Gu Z, Chen H, et al. Establishment of high-performance liquid chromatography and enzyme multiplied immunoassay technology methods for determination of free mycophenolic acid and its application in Chinese liver transplant recipients. Ther Drug Monit. 2010;32:653–60.PubMed CrossRef
  36.Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol. 1996;36:315–24.PubMed CrossRef
  37.Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet. 1998;34:429–55.PubMed CrossRef
  38.de Winter BC, Neumann I, van Hest RM, van Gelder T, Mathot RA. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease. Ther Drug Monit. 2009;31:382–90.PubMed CrossRef
  39.Tett SE, Saint-Marcoux F, Staatz CE, et al. Mycophenolate, clinical pharmacokinetics, formulations, and methods for assessing drug exposure. Transplant Rev (Orlando). 2011;25:47–57.PubMed CrossRef
  40.de Winter BC, van Gelder T, Sombogaard F, Shaw LM, van Hest RM, Mathot RA. Pharmacokinetic role of protein binding of mycophenolic acid and its glucuronide metabolite in renal transplant recipients. J Pharmacokinet Pharmacodyn. 2009;36:541–64.PubMed PubMedCentral CrossRef
  41.van Hest RM, van Gelder T, Vulto AG, Shaw LM, Mathot RA. Pharmacokinetic modelling of the plasma protein binding of mycophenolic acid in renal transplant recipients. Clin Pharmacokinet. 2009;48:463–76.PubMed CrossRef
  42.van Hest RM, Mathot RA, Pescovitz MD, Gordon R, Mamelok RD, van Gelder T. Explaining variability in mycophenolic acid exposure to optimize mycophenolate mofetil dosing: a population pharmacokinetic meta-analysis of mycophenolic acid in renal transplant recipients. J Am Soc Nephrol. 2006;17:871–80.PubMed CrossRef
  43.Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P. Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos. 2005;33:139–46.PubMed CrossRef
  44.Miles KK, Stern ST, Smith PC, Kessler FK, Ali S, Ritter JK. An investigation of human and rat liver microsomal mycophenolic acid glucuronidation: evidence for a principal role of UGT1A enzymes and species differences in UGT1A specificity. Drug Metab Dispos. 2005;33:1513–20.PubMed CrossRef
  45.Bernard O, Guillemette C. The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004;32:775–8.PubMed CrossRef
  46.Kobayashi M, Saitoh H, Kobayashi M, Tadano K, Takahashi Y, Hirano T. Cyclosporin A, but not tacrolimus, inhibits the biliary excretion of mycophenolic acid glucuronide possibly mediated by multidrug resistance-associated protein 2 in rats. J Pharmacol Exp Ther. 2004;309:1029–35.PubMed CrossRef
  47.Hesselink DA, van Hest RM, Mathot RA, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant. 2005;5:987–94.PubMed CrossRef
  48.Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet. 2007;46:13–58.PubMed CrossRef
  49.Naderer OJ, Dupuis RE, Heinzen EL, Wiwattanawongsa K, Johnson MW, Smith PC. The influence of norfloxacin and metronidazole on the disposition of mycophenolate mofetil. J Clin Pharmacol. 2005;45:219–26.PubMed CrossRef
  50.de Winter BC, van Gelder T, Glander P, et al. Population pharmacokinetics of mycophenolic acid : a comparison between enteric-coated mycophenolate sodium and mycophenolate mofetil in renal transplant recipients. Clin Pharmacokinet. 2008;47:827–38.PubMed CrossRef
  51.van Hest RM, van Gelder T, Bouw R, et al. Time-dependent clearance of mycophenolic acid in renal transplant recipients. Br J Clin Pharmacol. 2007;63:741–52.PubMed PubMedCentral CrossRef
  52.Shum B, Duffull SB, Taylor PJ, Tett SE. Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil. Br J Clin Pharmacol. 2003;56:188–97.PubMed PubMedCentral CrossRef
  53.van Hest RM, van Gelder T, Vulto AG, Mathot RA. Population pharmacokinetics of mycophenolic acid in renal transplant recipients. Clin Pharmacokinet. 2005;44:1083–96.PubMed CrossRef
  54.Musuamba FT, Rousseau A, Bosmans JL, et al. Limited sampling models and Bayesian estimation for mycophenolic acid area under the curve prediction in stable renal transplant patients co-medicated with ciclosporin or sirolimus. Clin Pharmacokinet. 2009;48:745–58.PubMed CrossRef
  55.Staatz CE, Duffull SB, Kiberd B, Fraser AD, Tett SE. Population pharmacokinetics of mycophenolic acid during the first week after renal transplantation. Eur J Clin Pharmacol. 2005;61:507–16.PubMed CrossRef
  56.Jaklic A, Collins CJ, Mrhar A, et al. High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients. Int J Clin Pharmacol Ther. 2013;51:711–7.PubMed PubMedCentral
  57.Ratna P, Mathew BS, Annapandian VM, et al. Pharmacokinetic drug interaction of mycophenolate with co-amoxiclav in renal transplant patients. Transplantation. 2011;91:e36–8.PubMed CrossRef
  58.Borrows R, Chusney G, Loucaidou M, et al. Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity. Am J Transplant. 2006;6:121–8.PubMed CrossRef
  59.Kaplan B, Meier-Kriesche HU, Friedman G, et al. The effect of renal insufficiency on mycophenolic acid protein binding. J Clin Pharmacol. 1999;39:715–20.PubMed CrossRef
  60.Kuypers DR, Vanrenterghem Y, Squifflet JP, et al. Twelve-month evaluation of the clinical pharmacokinetics of total and free mycophenolic acid and its glucuronide metabolites in renal allograft recipients on low dose tacrolimus in combination with mycophenolate mofetil. Ther Drug Monit. 2003;25:609–22.PubMed CrossRef
  61.Weber LT, Shipkova M, Lamersdorf T, et al. Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients. J Am Soc Nephrol. 1998;9:1511–20.PubMed
  62.Gonzalez-Roncero FM, Govantes MA, Chaves VC, Palomo PP, Serra MB. Influence of renal insufficiency on pharmacokinetics of ACYL-glucuronide metabolite of mycophenolic acid in renal transplant patients. Transplant Proc. 2007;39:2176–8.PubMed CrossRef
  63.Shaw LM, Mick R, Nowak I, Korecka M, Brayman KL. Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function. J Clin Pharmacol. 1998;38:268–75.PubMed CrossRef
  64.Jacobson PA, Rydhom N, Huang J, Baker KS, Verneris MR. High-unbound mycophenolic acid concentrations in an infant on peritoneal dialysis following hematopoietic cell transplant. Bone Marrow Transplant. 2007;40:911–2.PubMed CrossRef
  65.Weber LT, Shipkova M, Armstrong VW, et al. The pharmacokinetic-pharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients: a report of the german study group on mycophenolate mofetil therapy. J Am Soc Nephrol. 2002;13:759–68.PubMed CrossRef
  66.Bubalo J, Carpenter PA, Majhail N, et al. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee. Biol Blood Marrow Transplant. 2014;20:600–16.PubMed CrossRef
  67.Laverdière I, Caron P, Couture F, Guillemette C, Levesque E. Liquid chromatography-coupled tandem mass spectrometry based assay to evaluate inosine-5’-monophosphate dehydrogenase activity in peripheral blood mononuclear cells from stem cell transplant recipients. Anal Chem. 2012;84:216–23.PubMed CrossRef
  68.Albrecht W, Storck M, Pfetsch E, Martin W, Abendroth D. Development and application of a high-performance liquid chromatography-based assay for determination of the activity of inosine 5’-monophosphate dehydrogenase in whole blood and isolated mononuclear cells. Ther Drug Monit. 2000;22:283–94.PubMed CrossRef
  69.Bemer MJ, Risler LJ, Phillips BR, et al. Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:1544–52.PubMed PubMedCentral CrossRef
  70.Glander P, Hambach P, Braun KP, et al. Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation. Am J Transplant. 2004;4:2045–51.PubMed CrossRef
  71.Maris MB, Sandmaier BM, Storer BE, et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant. 2006;12:454–65.PubMed CrossRef
  72.Harnicar S, Ponce DM, Hilden P, et al. Intensified mycophenolate mofetil dosing and higher mycophenolic acid trough levels reduce severe acute graft-versus-host disease after double-unit cord blood transplantation. Biol Blood Marrow Transplant. 2015;21:920–5.PubMed CrossRef
  73.Bejanyan N, Rogosheske J, DeFor T, et al. Higher dose of mycophenolate mofetil reduces acute graft-versus-host disease in reduced-intensity conditioning double umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2015;21:926–33.PubMed PubMedCentral CrossRef
  74.Kornblit B, Maloney DG, Storb R, et al. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013;19:1340–7.PubMed PubMedCentral CrossRef
  75.Saint-Marcoux F, Guigonis V, Decramer S, et al. Development of a Bayesian estimator for the therapeutic drug monitoring of mycophenolate mofetil in children with idiopathic nephrotic syndrome. Pharmacol Res. 2011;63:423–31.PubMed CrossRef
  76.Barraclough KA, Staatz CE, Isbel NM, Johnson DW. Therapeutic monitoring of mycophenolate in transplantation: is it justified? Curr Drug Metab. 2009;10:179–87.PubMed CrossRef
  77.McDermott CL, Sandmaier BM, Storer B, et al. Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2013;19:1159–66.PubMed PubMedCentral CrossRef
  78.Arai Y, Kondo T, Kitano T, et al. Monitoring mycophenolate mofetil is necessary for the effective prophylaxis of acute GVHD after cord blood transplantation. Bone Marrow Transplant. 2015;50:312–4.PubMed CrossRef
  79.Ng J, Rogosheske J, Barker J, Weisdorf D, Jacobson PA. A limited sampling model for estimation of total and unbound mycophenolic acid (MPA) area under the curve (AUC) in hematopoietic cell transplantation (HCT). Ther Drug Monit. 2006;28:394–401.PubMed CrossRef
  80.Al-Kadhimi Z, Gul Z, Chen W, et al. High incidence of severe acute graft-versus-host disease with tacrolimus and mycophenolate mofetil in a large cohort of related and unrelated allogeneic transplantation patients. Biol Blood Marrow Transplant. 2014;20:979–85.PubMed PubMedCentral CrossRef
  81.Cutler C, Antin JH. Sirolimus for GVHD prophylaxis in allogeneic stem cell transplantation. Bone Marrow Transplant. 2004;34:471–6.PubMed CrossRef
  82.Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003;35:7S–14S.PubMed CrossRef
  83.Cutler C, Stevenson K, Kim HT, et al. Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant. 2011;46:659–67.PubMed PubMedCentral CrossRef
  84.Ho VT, Aldridge J, Kim HT, et al. Comparison of tacrolimus and sirolimus (Tac/Sir) versus tacrolimus, sirolimus, and mini-methotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:844–50.PubMed PubMedCentral CrossRef
  85.Nakamura R, Palmer JM, O’Donnell MR, et al. Reduced intensity allogeneic hematopoietic stem cell transplantation for MDS using tacrolimus/sirolimus-based GVHD prophylaxis. Leuk Res. 2012;36:1152–6.PubMed PubMedCentral CrossRef
  86.Perez-Simon JA, Martino R, Parody R, et al. The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate. Haematologica. 2013;98:526–32.PubMed PubMedCentral CrossRef
  87.Rodriguez R, Nakamura R, Palmer JM, et al. A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens. Blood. 2010;115:1098–105.PubMed PubMedCentral CrossRef
  88.Schleuning M, Judith D, Jedlickova Z, et al. Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study. Bone Marrow Transplant. 2009;43:717–23.PubMed CrossRef
  89.Snyder DS, Palmer J, Gaal K, et al. Improved outcomes using tacrolimus/sirolimus for graft-versus-host disease prophylaxis with a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplant as treatment of myelofibrosis. Biol Blood Marrow Transplant. 2010;16:281–6.PubMed PubMedCentral CrossRef
  90.Kornblit B, Maloney DG, Storer BE, et al. A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after nonmyeloablative unrelated donor transplantation. Haematologica. 2014;99:1624–31.PubMed PubMedCentral CrossRef
  91.Ciancio G, Burke GW, Gaynor JJ, et al. A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year. Transplantation. 2004;77:244–51.PubMed CrossRef
  92.Ciancio G, Burke GW, Gaynor JJ, et al. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year. Transplantation. 2004;77:252–8.PubMed CrossRef
  93.Koenen HJ, Michielsen EC, Verstappen J, Fasse E, Joosten I. Superior T-cell suppression by rapamycin and FK506 over rapamycin and cyclosporine A because of abrogated cytotoxic T-lymphocyte induction, impaired memory responses, and persistent apoptosis. Transplantation. 2003;75:1581–90.PubMed CrossRef
  94.Pulsipher MA, Langholz B, Wall DA, et al. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children’s Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood. 2014;123:2017–25.PubMed PubMedCentral CrossRef
  95.Cutler C, Logan B, Nakamura R, et al. Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood. 2014;124:1372–7.PubMed PubMedCentral CrossRef
  96.Wolff D, Andree H, Hilgendorf I, Casper J, Freund M, Junghanss C. Sirolimus in combination with tacrolimus in allogeneic stem cell transplantation–timing and conditioning regimen may be crucial. Biol Blood Marrow Transplant. 2008;14:942–3.PubMed CrossRef
  97.Khaled SK, Palmer J, Stiller T, et al. A phase II study of sirolimus, tacrolimus and rabbit anti-thymocyte globulin as GVHD prophylaxis after unrelated-donor PBSC transplant. Bone Marrow Transplant. 2013;48:278–83.PubMed PubMedCentral CrossRef
  98.Claxton DF, Ehmann C, Rybka W. Control of advanced and refractory acute myelogenous leukaemia with sirolimus-based non-myeloablative allogeneic stem cell transplantation. Br J Haematol. 2005;130:256–64.PubMed CrossRef
  99.Alyea EP, Li S, Kim HT, et al. Sirolimus, tacrolimus, and low-dose methotrexate as graft-versus-host disease prophylaxis in related and unrelated donor reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:920–6.PubMed PubMedCentral CrossRef
  100.Stenton SB, Partovi N, Ensom MH. Sirolimus: the evidence for clinical pharmacokinetic monitoring. Clin Pharmacokinet. 2005;44:769–86.PubMed CrossRef
  101.Mahalati K, Kahan BD. Clinical pharmacokinetics of sirolimus. Clin Pharmacokinet. 2001;40:573–85.PubMed CrossRef
  102.Schachter AD, Meyers KE, Spaneas LD, et al. Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol. Pediatr Transplant. 2004;8:171–7.PubMed PubMedCentral CrossRef
  103.Schubert M, Venkataramanan R, Holt DW, et al. Pharmacokinetics of sirolimus and tacrolimus in pediatric transplant patients. Am J Transplant. 2004;4:767–73.PubMed CrossRef
  104.Goyal RK, Han K, Wall DA, et al. Sirolimus pharmacokinetics in early postmyeloablative pediatric blood and marrow transplantation. Biol Blood Marrow Transplant. 2013;19:569–75.PubMed PubMedCentral CrossRef
  105.Schmid RW, Lotz J, Schweigert R, et al. Multi-site analytical evaluation of a chemiluminescent magnetic microparticle immunoassay (CMIA) for sirolimus on the Abbott ARCHITECT analyzer. Clin Biochem. 2009;42:1543–8.PubMed CrossRef
  106.Marty FM, Lowry CM, Cutler CS, et al. Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006;12:552–9.PubMed CrossRef
  107.Shayani S, Palmer JM, Stiller T, et al. Aprepitant (Emend) significantly increases sirolimus levels in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant. 2012;47:291–3.PubMed CrossRef
  108.Kubiak DW, Koo S, Hammond SP, et al. Safety of posaconazole and sirolimus coadministration in allogeneic hematopoietic stem cell transplants. Biol Blood Marrow Transplant. 2012;18:1462–5.PubMed CrossRef
  109.Said A, Garnick JJ, Dieterle N, Peres E, Abidi MH, Ibrahim RB. Sirolimus-itraconazole interaction in a hematopoietic stem cell transplant recipient. Pharmacotherapy. 2006;26:289–95.PubMed CrossRef
  110.Rapamune product information. 2015. Available at: http://​labeling.​pfizer.​com/​showlabeling.​aspx?​id=​139 . Accessed 3 Sept 2015.
  111.Zimmerman JJ, Lasseter KC, Lim HK, et al. Pharmacokinetics of sirolimus (rapamycin) in subjects with mild to moderate hepatic impairment. J Clin Pharmacol. 2005;45:1368–72.PubMed CrossRef
  112.Zimmerman JJ, Patat A, Parks V, Moirand R, Matschke K. Pharmacokinetics of sirolimus (rapamycin) in subjects with severe hepatic impairment. J Clin Pharmacol. 2008;48:285–92.PubMed CrossRef
  113.Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39:215–31.PubMed CrossRef
  114.Antin JH, Kim HT, Cutler C, et al. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003;102:1601–5.PubMed CrossRef
  115.Johnston L, Florek M, Armstrong R, et al. Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47:581–8.PubMed PubMedCentral CrossRef
  116.Shayani S, Palmer J, Stiller T, et al. Thrombotic microangiopathy associated with sirolimus level after allogeneic hematopoietic cell transplantation with tacrolimus/sirolimus-based graft-versus-host disease prophylaxis. Biol Blood Marrow Transplant. 2013;19:298–304.PubMed PubMedCentral CrossRef
  117.Kiel PJ, Vargo CA, Patel GP, Rosenbeck LL, Srivastava S. Possible correlation of sirolimus plasma concentration with sinusoidal obstructive syndrome of the liver in patients undergoing myeloablative allogeneic hematopoietic cell transplantation. Pharmacotherapy. 2012;32:441–5.PubMed CrossRef
  118.Theurich S, Fischmann H, Shimabukuro-Vornhagen A, et al. 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.
  119.Storb R, Kolb HJ, Graham TC, Kolb H, Weiden PL, Thomas ED. Treatment of established graft-versus-host disease in dogs by antithymocyte serum or prednisone. Blood. 1973;42:601–9.PubMed
  120.Storb R, Gluckman E, Thomas ED, et al. Treatment of established human graft-versus-host disease by antithymocyte globulin. Blood. 1974;44:56–75.PubMed
  121.Ruutu T, Gratwohl A, de Witte T, et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2014;49:168–73.PubMed CrossRef
  122.Angelucci E, Matthes-Martin S, Baronciani D, et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99:811–20.PubMed PubMedCentral CrossRef
  123.Radhakrishnan K, Bhatia M, Geyer MB, et al. Busulfan, fludarabine, and alemtuzumab conditioning and unrelated cord blood transplantation in children with sickle cell disease. Biol Blood Marrow Transplant. 2013;19:676–7.PubMed CrossRef
  124.Poire X, van Besien K. Alemtuzumab in allogeneic hematopoetic stem cell transplantation. Expert Opin Biol Ther. 2011;11:1099–111.PubMed PubMedCentral CrossRef
  125.Morris EC, Rebello P, Thomson KJ, et al. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood. 2003;102:404–6.PubMed CrossRef
  126.Chawla S, Dharmani-Khan P, Liu Y, et al. High serum level of antithymocyte globulin immediately before graft infusion is associated with a low likelihood of chronic, but not acute, graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:1156–62.PubMed CrossRef
  127.Vo PT, Pantin J, Ramos C, et al. Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor. J Hematol Oncol. 2015;8:78.PubMed PubMedCentral CrossRef
  128.Appelbaum FR, Bacigalupo A, Soiffer R. Anti-T cell antibodies as part of the preparative regimen in hematopoietic cell transplantation–a debate. Biol Blood Marrow Transplant. 2012;18:S111–5.PubMed PubMedCentral CrossRef
  129.Feng X, Scheinberg P, Biancotto A, et al. In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. Haematologica. 2014;99:1433–40.PubMed PubMedCentral CrossRef
  130.Ballen KK. ATG for cord blood transplant: yes or no? Blood. 2014;123:7–8.PubMed CrossRef
  131.Waller EK, Langston AA, Lonial S, et al. Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant. 2003;9:460–71.PubMed CrossRef
  132.Ram R, Storb R. Pharmacologic prophylaxis regimens for acute graft-versus-host disease: past, present and future. Leuk Lymphoma. 2013;54:1591–601.PubMed PubMedCentral CrossRef
  133.Sangiolo D, Storb R, Deeg HJ, et al. Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biol Blood Marrow Transplant. 2010;16:1411–8.PubMed PubMedCentral CrossRef
  134.Remberger M, Sundberg B. Rabbit-immunoglobulin G levels in patients receiving thymoglobulin as part of conditioning before unrelated donor stem cell transplantation. Haematologica. 2005;90:931–8.PubMed
  135.Bacigalupo A, Lamparelli T, Bruzzi 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.PubMed CrossRef
  136.Kumar A, Mhaskar AR, Reljic T, et al. Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review. Leukemia. 2012;26:582–8.PubMed CrossRef
  137.Theurich S, Fischmann H, Chakupurakal G, et al. Anti-thymocyte globulins for post-transplant graft-versus-host disease prophylaxis: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2013;88:178–86.PubMed CrossRef
  138.Seidel MG, Fritsch G, Matthes-Martin S, et al. Antithymocyte globulin pharmacokinetics in pediatric patients after hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2005;27:532–6.PubMed CrossRef
  139.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.PubMed CrossRef
  140.Eiermann TH, Lambrecht P, Zander AR. Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant. 1999;23:779–81.PubMed CrossRef
  141.Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N. Heterogeneous clearance of antithymocyte globulin after CD34+-selected allogeneic hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant. 2005;11:609–18.PubMed CrossRef
  142.Call SK, Kasow KA, Barfield R, et al. Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15:274–8.PubMed PubMedCentral CrossRef
  143.Hannon M, Beguin Y, Ehx G, et al. Immune recovery after allogeneic hematopoietic stem cell transplantation following Flu-TBI versus TLI-ATG conditioning. Clin Cancer Res. 2015;21:3131–9.PubMed CrossRef
  144.Remberger M, Sundberg B. Low serum levels of total rabbit-IgG is associated with acute graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation: results from a prospective study. Biol Blood Marrow Transplant. 2009;15:996–9.PubMed CrossRef
  145.Podgorny PJ, Ugarte-Torres A, Liu Y, Williamson TS, Russell JA, Storek J. High rabbit-antihuman thymocyte globulin levels are associated with low likelihood of graft-vs-host disease and high likelihood of posttransplant lymphoproliferative disorder. Biol Blood Marrow Transplant. 2010;16:915–26.PubMed CrossRef
  146.Jol-van der Zijde CM, Bredius RG, Jansen-Hoogendijk AM, et al. IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD. Bone Marrow Transplant. 2012;47:360–8.PubMed CrossRef
  147.Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49:633–59.PubMed CrossRef
  148.© University of Washington 1999–2014. UW metabolism and transport drug interaction database. https://​www.​druginteractioni​nfo.​org/​span> . Accessed 2 Jan 2015.
  149.Yamane A, Mori T, Kato J, Ono Y, Okamoto S. Discrepancy in the kinetics of total and active anti-thymocyte globulin blood concentrations in recipients of allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2011;93:406–7.PubMed CrossRef
  150.Regan JF, Lyonnais C, Campbell K, Smith LV, Buelow R. Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations. Transpl Immunol. 2001;9:29–36.PubMed CrossRef
  151.Lindemans CA, Chiesa R, Amrolia PJ, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood. 2014;123:126–32.PubMed CrossRef
  152.Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–26.PubMed CrossRef
  153.McCune JS, Bemer MJ, Barrett JS, Scott Baker K, Gamis AS, Holford NH. Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and bayesian dose personalization. Clin Cancer Res. 2014;20:754–63.PubMed PubMedCentral CrossRef
  154.Oellerich M, Armstrong VW. The role of therapeutic drug monitoring in individualizing immunosuppressive drug therapy: recent developments. Ther Drug Monit. 2006;28:720–5.PubMed
  155.Monchaud C, Marquet P. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part II. Clin Pharmacokinet. 2009;48:489–516.PubMed CrossRef
  156.Monchaud C, Marquet P. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part I. Clin Pharmacokinet. 2009;48:419–62.PubMed PubMedCentral CrossRef
  157.Le Meur Y, Borrows R, Pescovitz MD, et al. Therapeutic drug monitoring of mycophenolates in kidney transplantation: report of The Transplantation Society consensus meeting. Transplant Rev (Orlando). 2011;25:58–64.PubMed CrossRef
  158.Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314:729–35.PubMed CrossRef
  159.Kennedy MS, Yee GC, McGuire TR, Leonard TM, Crowley JJ, Deeg HJ. Correlation of serum cyclosporine concentration with renal dysfunction in marrow transplant recipients. Transplantation. 1985;40:249–53.PubMed CrossRef
  160.Martin P, Bleyzac N, Souillet G, et al. Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors. Bone Marrow Transplant. 2003;32:777–84.PubMed CrossRef
  161.Ram R, Storer B, Mielcarek M, et al. Association between calcineurin inhibitor blood concentrations and outcomes after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18:414–22.PubMed PubMedCentral CrossRef
  162.Gerard C, Bleyzac N, Girard P, Freyer G, Bertrand Y, Tod M. Links between cyclosporin exposure in tissues and graft-versus-host disease in pediatric bone marrow transplantation: analysis by a PBPK model. Pharm Res. 2011;28:531–9.PubMed CrossRef
  163.Chao NJ, Sullivan KM. Pharmacologic prevention of acute graft-versus-host disease. In: Appelbaum FR, Forman SJ, Negrin RS, Blume KG, editors. Thomas’ hematopoietic cell transplantation. 4th ed. West Sussex: Blackwell Publishing; 2009. p. 1257–74.CrossRef
  164.de Jonge H, de Loor H, Verbeke K, Vanrenterghem Y, Kuypers DR. In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients. Clin Pharmacol Ther. 2012;92:366–75.PubMed CrossRef
  165.de Jonge H, Kuypers DR. Response to “Pretransplantation pharmacokinetic assessments to predict posttransplantation dosing requirements in renal transplant recipients: what is known?”. Clin Pharmacol Ther. 2013;93:307–8.PubMed CrossRef
  166.van Maarseveen E, van Zuilen AD. Pretransplantation pharmacokinetic assessments to predict posttransplantation dosing requirements in renal transplant recipients: what is known? Clin Pharmacol Ther. 2013;93:306–7.PubMed CrossRef
  167.Utecht KN, Hiles JJ, Kolesar J. Effects of genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors. Am J Health Syst Pharm. 2006;63:2340–8.PubMed CrossRef
  168.Koh Y, Kim I, Shin DY, et al. Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine blood levels and clinical outcomes in patients who receive allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18:37–43.PubMed CrossRef
  169.Qiu F, He XJ, Sun YX, Li-Ling J, Zhao LM. Influence of ABCB1, CYP3A4*18B and CYP3A5*3 polymorphisms on cyclosporine A pharmacokinetics in bone marrow transplant recipients. Pharmacol Rep. 2011;63:815–25.PubMed CrossRef
  170.Onizuka M, Kunii N, Toyosaki M, et al. Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients. Bone Marrow Transplant. 2011;46:1113–7.PubMed CrossRef
  171.McCune JS, Jacobson P, Wiseman A, Militano O. Optimizing drug therapy in pediatric SCT: focus on pharmacokinetics. Bone Marrow Transplant. 2015;50(2):165–72.PubMed CrossRef
  172.Trame MN, Bergstrand M, Karlsson MO, Boos J, Hempel G. Population pharmacokinetics of busulfan in children: increased evidence for body surface area and allometric body weight dosing of busulfan in children. Clin Cancer Res. 2011;17:6867–77.PubMed CrossRef
  173.Anderson BJ, Holford NH. Mechanistic basis of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet. 2009;24:25–36.PubMed CrossRef
  174.Bleyzac N, Souillet G, Magron P, et al. Improved clinical outcome of paediatric bone marrow recipients using a test dose and Bayesian pharmacokinetic individualization of busulfan dosage regimens. Bone Marrow Transplant. 2001;28:743–51.PubMed CrossRef
  175.McCune JS, Batchelder A, Guthrie KA, et al. Personalized dosing of cyclophosphamide in the total body irradiation-cyclophosphamide conditioning regimen: a phase II trial in patients with hematologic malignancy. Clin Pharmacol Ther. 2009;85:615–22.PubMed PubMedCentral CrossRef
  176.Neely M, Jelliffe R. Practical, individualized dosing: 21st century therapeutics and the clinical pharmacometrician. J Clin Pharmacol. 2010;50:842–7.PubMed CrossRef
  177.McMichael J, Lieberman R, Doyle H, McCauley J, Fung J, Starzl TE. An intelligent and cost-effective computer dosing system for individualizing FK506 therapy in transplantation and autoimmune disorders. J Clin Pharmacol. 1993;33:599–605.PubMed PubMedCentral CrossRef
  178.Barrett JS, Mondick JT, Narayan M, Vijayakumar K, Vijayakumar S. Integration of modeling and simulation into hospital-based decision support systems guiding pediatric pharmacotherapy. BMC Med Inform Decis Mak. 2008;8:6.PubMed PubMedCentral CrossRef
  179.Kuypers DR, de Jonge H, Naesens M, Vanrenterghem Y. Effects of CYP3A5 and MDR1 single nucleotide polymorphisms on drug interactions between tacrolimus and fluconazole in renal allograft recipients. Pharmacogenet Genom. 2008;18:861–8.CrossRef
  180.Kuypers DR, de Loor H, Naesens M, Coopmans T, de Jonge H. Combined effects of CYP3A5*1, POR*28, and CYP3A4*22 single nucleotide polymorphisms on early concentration-controlled tacrolimus exposure in de-novo renal recipients. Pharmacogenet Genom. 2014;24:597–606.CrossRef
  181.Lee SJ, Joffe S, Artz AS, et al. Individual physician practice variation in hematopoietic cell transplantation. J Clin Oncol. 2008;26:2162–70.PubMed CrossRef
  182.Petersdorf EW. HLA matching in allogeneic stem cell transplantation. Curr Opin Hematol. 2004;11:386–91.PubMed CrossRef
  183.Hansen JA, Chien JW, Warren EH, Zhao LP, Martin PJ. Defining genetic risk for graft-versus-host disease and mortality following allogeneic hematopoietic stem cell transplantation. Curr Opin Hematol. 2010;17:483–92.PubMed PubMedCentral CrossRef
  184.Dupuis LL, Seto W, Teuffel O, et al. Prediction of area under the cyclosporine concentration versus time curve in children undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:418–23.PubMed CrossRef
  185.Beal SL, Sheiner LB. Estimating population kinetics. Crit Rev Biomed Eng. 1982;8:195–222.PubMed
  186.Holford NH, Kimko HC, Monteleone JP, Peck CC. Simulation of clinical trials. Annu Rev Pharmacol Toxicol. 2000;40:209–34.PubMed CrossRef
  187.Nelson RP Jr, Khawaja MR, Perkins SM, et al. Prognostic biomarkers for acute graft-versus-host disease risk after cyclophosphamide-fludarabine nonmyeloablative allotransplantation. Biol Blood Marrow Transplant. 2014;20:1861–4.PubMed PubMedCentral CrossRef
  188.Ioannidis JP, Loy EY, Poulton R, Chia KS. Researching genetic versus nongenetic determinants of disease: a comparison and proposed unification. Sci Transl Med. 2009;1:7ps8.
  189.Gu H, Gowda GA, Raftery D. Metabolic profiling: are we en route to better diagnostic tests for cancer? Future Oncol. 2012;8:1207–10.PubMed PubMedCentral CrossRef
  190.Weissinger EM, Metzger J, Dobbelstein C, et al. Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation. Leukemia. 2014;28:842–52.PubMed CrossRef
  191.Levine JE, Logan BR, Wu J, et al. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012;119:3854–60.PubMed PubMedCentral CrossRef
  192.Loo RL, Chan Q, Brown IJ, et al. A comparison of self-reported analgesic use and detection of urinary ibuprofen and acetaminophen metabolites by means of metabonomics: the INTERMAP Study. Am J Epidemiol. 2012;175:348–58.PubMed PubMedCentral CrossRef
  193.Cunningham K, Claus SP, Lindon JC, et al. Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response. J Proteome Res. 2012;11:4630–42.PubMed CrossRef
  194.Coen M, Goldfain-Blanc F, Rolland-Valognes G, et al. Pharmacometabonomic investigation of dynamic metabolic phenotypes associated with variability in response to galactosamine hepatotoxicity. J Proteome Res. 2012;11:2427–40.PubMed CrossRef
  195.Chen C, Krausz KW, Idle JR, Gonzalez FJ. Identification of novel toxicity-associated metabolites by metabolomics and mass isotopomer analysis of acetaminophen metabolism in wild-type and Cyp2e1-null mice. J Biol Chem. 2008;283:4543–59.PubMed PubMedCentral CrossRef
  196.Li F, Patterson AD, Hofer CC, Krausz KW, Gonzalez FJ, Idle JR. Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QTOFMS-based metabolomics. Biochem Pharmacol. 2010;80:1063–74.PubMed PubMedCentral CrossRef
  197.Yao D, Shi X, Wang L, Gosnell BA, Chen C. Characterization of differential cocaine metabolism in mouse and rat through metabolomics-guided metabolite profiling. Drug Metab Dispos. 2013;41:79–88.PubMed PubMedCentral CrossRef
  198.Coen M, Lenz EM, Nicholson JK, Wilson ID, Pognan F, Lindon JC. An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy. Chem Res Toxicol. 2003;16:295–303.PubMed CrossRef
  199.Nicholson JK, Connelly J, Lindon JC, Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002;1:153–61.PubMed CrossRef
  200.Blood samples to identify biomarkers of busulfan. Clinicaltrials.gov identifier: NCT02291965 (PI: Jeannine S. McCune). Available at https://​clinicaltrials.​gov/​ct2/​show/​NCT02291965 . Accessed 7 Sep 2015.
  201.Tiziani S, Lodi A, Khanim FL, Viant MR, Bunce CM, Gunther UL. Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines. PLoS One. 2009;4:e4251.PubMed PubMedCentral CrossRef
  202.Kim CD, Kim EY, Yoo H, et al. Metabonomic analysis of serum metabolites in kidney transplant recipients with cyclosporine A- or tacrolimus-based immunosuppression. Transplantation. 2010;90:748–56.PubMed CrossRef
  203.Iyengar R, Zhao S, Chung SW, Mager DE, Gallo JM. Merging systems biology with pharmacodynamics. Sci Transl Med. 2012;4:126ps7.
  204.Huang AY, Haining WN, Barkauskas DS, et al. Viewing transplantation immunology through today’s lens: new models, new imaging, and new insights. Biol Blood Marrow Transplant. 2013;19:S44–51.PubMed PubMedCentral CrossRef
  205.Palsson S, Hickling TP, Bradshaw-Pierce EL, et al. The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models. BMC Syst Biol. 2013;7:95.PubMed PubMedCentral CrossRef
  206.Kiehl MG, Shipkova M, Basara N, et al. Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite. Clin Biochem. 2000;33:203–8.PubMed CrossRef
  207.Furlong T, Martin P, Flowers ME, et al. Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant. 2009;44:739–48.PubMed PubMedCentral CrossRef
  208.Jacobson PA, Huang J, Wu J, et al. Mycophenolate pharmacokinetics and association with response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant. 2010;16:421–9.PubMed PubMedCentral CrossRef
  209.Hiwarkar P, Shaw BE, Tredger JM, et al. Mycophenolic acid trough level monitoring: relevance in acute and chronic graft versus host disease and its relation with albumin. Clin Transplant. 2011;25:222–7.PubMed CrossRef
  210.Basara N, Blau WI, Kiehl MG, et al. Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients. Clin Transplant. 2000;14:121–6.PubMed CrossRef
  211.Pidala J, Kim J, Jim H, et al. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012;97:1882–9.PubMed PubMedCentral CrossRef
  212.Benito AI, Furlong T, Martin PJ, et al. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72:1924–9.PubMed CrossRef
  213.Pidala J, Kim J, Anasetti C. Sirolimus as primary treatment of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2009;15:881–5.PubMed CrossRef
  214.Johnston LJ, Brown J, Shizuru JA, et al. Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11:47–55.PubMed CrossRef
  215.Cutler C, Li S, Ho VT, et al. Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation. Blood. 2007;109:3108–14.PubMed PubMedCentral
  216.Pulsipher MA, Wall DA, Grimley M, et al. A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL). Br J Haematol. 2009;147:691–9.PubMed PubMedCentral CrossRef
  217.Furlong T, Kiem HP, Appelbaum FR, et al. Sirolimus in combination with cyclosporine or tacrolimus plus methotrexate for prevention of graft-versus-host disease following hematopoietic cell transplantation from unrelated donors. Biol Blood Marrow Transplant. 2008;14:531–7.PubMed PubMedCentral CrossRef
  218.Rosenbeck LL, Kiel PJ, Kalsekar I, et al. Prophylaxis with sirolimus and tacrolimus +/− antithymocyte globulin reduces the risk of acute graft-versus-host disease without an overall survival benefit following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:916–22.PubMed CrossRef
  219.Hsieh MM, Kang EM, Fitzhugh CD, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361:2309–17.PubMed PubMedCentral CrossRef
  220.Floisand Y, Brinch L, Gedde-Dahl T, et al. Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47:1552–7.PubMed CrossRef
  221.McCune JS, Bemer MJ. Pharmacokinetics, pharmacodynamics, and pharmacogenomics of immunosuppressants in allogeneic hematopoietic cell transplantation: Part I. Clin Pharmacokinet. 2015. doi:10.​1007/​s40262-015-0339-2 .
  
• 作者单位：Jeannine S. McCune (1) (2) (3)
  Meagan J. Bemer (2)
  Janel Long-Boyle (4)
  
  1. Department of Pharmacy, University of Washington, Box 357630, Seattle, WA, 98195, USA
  2. Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA, 98195, USA
  3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  4. Department of Clinical Pharmacy, University of California San Francisco, San Francisco, CA, 94131, USA
  
• 刊物主题：Pharmacotherapy; Pharmacology/Toxicology; Internal Medicine;
• 出版者：Springer International Publishing
• ISSN：1179-1926

文摘

Part I of this article included a pertinent review of allogeneic hematopoietic cell transplantation (alloHCT), the role of postgraft immunosuppression in alloHCT, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of the calcineurin inhibitors and methotrexate. In this article (Part II), we review the pharmacokinetics, pharmacodynamics, and pharmacogenomics of mycophenolic acid (MPA), sirolimus, and the antithymocyte globulins (ATG). We then discuss target concentration intervention (TCI) of these postgraft immunosuppressants in alloHCT patients, with a focus on current evidence for TCI and on how TCI may improve clinical management in these patients. Currently, TCI using trough concentrations is conducted for sirolimus in alloHCT patients. Several studies demonstrate that MPA plasma exposure is associated with clinical outcomes, with an increasing number of alloHCT patients needing TCI of MPA. Compared with MPA, there are fewer pharmacokinetic/dynamic studies of rabbit ATG and horse ATG in alloHCT patients. Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include ‘–omics’-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses.