Skip to main content
SpringerLink
Log in

Pharmacotherapy in Pediatric Hematopoietic Cell Transplantation

  • Chapter
  • First Online:
Pediatric Pharmacotherapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 261))

Abstract

Hematopoietic cell transplantation (HCT) is a curative treatment option for both malignant and nonmalignant diseases. Success of the procedure mainly depends on disease control and treatment-related complications. Pharmacotherapy plays a major role in HCT and significantly impacts the outcomes. Main drug use within HCT includes conditioning, GvHD prophylaxis, and prevention/treatment of infections.

Increasing evidence suggests individualized dosing in (pediatric) HCT may improve outcome. Dose individualization may result in a better predictable drug treatment in terms of safety and efficacy, including timely immune reconstitution after HCT and optimal tumor or disease control, which may result in improved survival chances.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Admiraal R, van Kesteren C, Jol-van Der Zijde CM et al (2015) Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haematopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis. Lancet Haematol 2:e194–e203

    PubMed  Google Scholar 

  • Admiraal R, de Koning C, Lindemans CA et al (2017a) Viral reactivations and associated outcomes in context of immune reconstitution after pediatric hematopoietic cell transplantation. J Allergy Clin Immunol 140(6):1643–1650

    PubMed  Google Scholar 

  • Admiraal R, Nierkens S, de Witte MA et al (2017b) Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharmacodynamic cohort analysis. Lancet Haematol. https://doi.org/10.1016/S2352-3026(15)00045-9

  • Akan H, Antia VP, Kouba M et al (2013) Preventing invasive fungal disease in patients with haematological malignancies and the recipients of haematopoietic stem cell transplantation: practical aspects. J Antimicrob Chemother 68(Suppl 3):iii5–ii16

    CAS  PubMed  Google Scholar 

  • Apperley J, Carreras E, Gluckman E, Masszi T (eds) (2012) ESH-EBMT handbook on haematopoietic stem cell transplantation. Forum Service Editore, Genoa

    Google Scholar 

  • Bartelink IH, Bredius RGM, Belitser SV et al (2009) Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant 15:231–241

    CAS  PubMed  Google Scholar 

  • Bartelink IH, van Kesteren C, Boelens JJ et al (2012a) Predictive performance of a busulfan pharmacokinetic model in children and young adults. Ther Drug Monit 34:574–583

    CAS  PubMed  Google Scholar 

  • Bartelink IH, Boelens JJ, Bredius RGM et al (2012b) Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: towards individualized dosing. Clin Pharmacokinet 51:331–345

    CAS  PubMed  Google Scholar 

  • Bartelink IH, van Reij EML, Gerhardt CE et al (2013a) 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 Transplant 20:1–9

    Google Scholar 

  • Bartelink IH, Belitser SV, Knibbe CAJ et al (2013b) Immune reconstitution kinetics as an early predictor for mortality using various hematopoietic stem cell sources in children. Biol Blood Marrow Transplant 19:305–313

    PubMed  Google Scholar 

  • Bartelink IH, Lalmohamed A, van Reij EML et al (2016) Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol 3:e526–e536

    PubMed  PubMed Central  Google Scholar 

  • Bauer RJ (2011) NONMEM 7.2 user manual. Available at https://iconplc.com

  • Bieri S, Roosnek E, Ozsahin H et al (2011) Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation. Eur J Haematol 87:138–147

    PubMed  Google Scholar 

  • Boelens JJ, Aldenhoven M, Purtill D et al (2013) Outcomes of transplantation using a various cell source in children with hurlers syndrome after myelo-ablative conditioning. an eurocord-EBMT-CIBMTR collaborative study. Blood 121:3981–3987

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bosch M, Dhadda M, Hoegh-Petersen M et al (2012) Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Cytotherapy 14:1258–1275

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brentjens RJ, Davila ML, Riviere I et al (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5:177ra38

    PubMed  PubMed Central  Google Scholar 

  • Brink MH, Ackaert O, Zwaveling J et al (2014) Pharmacokinetics of treosulfan in pediatric patients undergoing hematopoietic stem cell transplantation. Ther Drug Monit 36:465–472

    PubMed  Google Scholar 

  • Bruno B, Gooley T, Hackman RC, Davis C, Corey L, Boeckh M (2003) Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival. Biol Blood Marrow Transplant 9:341–352

    PubMed  Google Scholar 

  • Call SK, Kasow KA, Barfield R et al (2009) Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation. Biol Blood Marrow Transplant 15:274–278

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chiesa R, Gilmour K, Qasim W et al (2012) 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 156:656–666

    CAS  PubMed  Google Scholar 

  • Claas FHS et al (2016) Europdonor annual report 2015. Available at https://www.matchis.nl

  • Corbacioglu S, Cesaro S, Faraci M et al (2012) Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet 379:1301–1309

    CAS  PubMed  Google Scholar 

  • Davies SM, Ramsay NKC, Klein JP et al (2000) Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 18:340–347

    CAS  PubMed  Google Scholar 

  • de Haar C, Plantinga M, Blokland NJ et al (2015) Generation of a cord blood-derived Wilms Tumor 1 dendritic cell vaccine for AML patients treated with allogeneic cord blood transplantation. Oncoimmunology 4:e1023973

    PubMed  PubMed Central  Google Scholar 

  • de Koning C, Admiraal R, Nierkens S, Boelens JJ (2017) Immune reconstitution and outcomes after conditioning with anti-thymocyte-globulin in unrelated cord blood transplantation; the good, the bad, and the ugly. Stem Cell Investig 4:38

    PubMed  PubMed Central  Google Scholar 

  • Deol A, Lum LG (2010) Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 36:528–538

    PubMed  PubMed Central  Google Scholar 

  • Eapen M, Rocha V, Sanz G et al (2010) Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol 11:653–660

    PubMed  PubMed Central  Google Scholar 

  • El-Jawahri A, Li S, Ballen KK et al (2016) Phase II trial of reduced-intensity busulfan/clofarabine conditioning with allogeneic hematopoietic stem cell transplantation for patients with acute myeloid leukemia, myelodysplastic syndromes, and acute lymphoid leukemia. Biol Blood Marrow Transplant 22:80–85

    CAS  PubMed  Google Scholar 

  • EMEA (2007) Guideline on reporting the results of population pharmacokinetic analyses. Available at https://www.ema.europa.eu

  • Falkenburg JHF, Warren EH (2011) Graft versus leukemia reactivity after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 17:S33–S38

    PubMed  Google Scholar 

  • FDA (1999) Guidance for industry, population pharmacokinetics. Available at https://www.fda.gov/

  • Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550–1561

    CAS  PubMed  PubMed Central  Google Scholar 

  • Filipovich AH, Weisdorf D, Pavletic S et al (2005) National Institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 11:945–956

    PubMed  Google Scholar 

  • Friberg LE, Henningsson A, Maas H, Nguyen L, Karlsson MO (2002) Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol 20:4713–4721

    PubMed  Google Scholar 

  • Glucksberg H, Storb R, Fefer A et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18:295–304

    CAS  PubMed  Google Scholar 

  • Gotoh M, Yoshizawa S, Katagiri S et al (2014) Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2-4 acute graft-versus-host disease. Transpl Infect Dis 16:440–449

    CAS  PubMed  Google Scholar 

  • Gratwohl A, Passweg J, Baldomero H, Hermans J, Urbano-Ispizua A (2000) Hematopoietic stem cell transplantation in Europe 1998. Hematol J 1:333–350

    CAS  PubMed  Google Scholar 

  • Green DM, Kawashima T, Stovall M et al (2009) Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 27:2677–2685

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grimwade D, Freeman SD (2014) Review article defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”? Blood 124:3345–3355

    CAS  PubMed  Google Scholar 

  • Grupp SA, Kalos M, Barrett D et al (2013) Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. N Engl J Med 368:1509–1518

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gyurkocza B, Sandmaier BM (2014) Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood 124:344–353

    CAS  PubMed  PubMed Central  Google Scholar 

  • Heemskerk MBA, van Walraven SM, Cornelissen JJ et al (2005) How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more! Bone Marrow Transplant 35:645–652

    CAS  PubMed  Google Scholar 

  • Hiwarkar P, Gaspar HB, Gilmour K et al (2013) Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients. Bone Marrow Transplant 48:803–808

    CAS  PubMed  Google Scholar 

  • Hiwarkar P, Qasim W, Ricciardelli I et al (2015) Cord blood T cells mediate enhanced anti-tumor effects compared with adult peripheral blood T cells. Blood 126:2882–2891

    CAS  PubMed  Google Scholar 

  • Holtick U, Albrecht M, Chemnitz JM et al (1996) Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults. Cochrane Database Syst Rev 4:CD010189

    Google Scholar 

  • Hough R, Danby R, Russell N et al (2015) Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols. Br J Haematol:360–370

    Google Scholar 

  • Ince I, de Wildt SN, Tibboel D, Danhof M, Knibbe CAJ (2009) Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK – PD modeling. Drug Discov Today 14:316–320

    CAS  PubMed  Google Scholar 

  • Jol-van der Zijde C, Jansen-Hoogendijk A, Raaijmakers S et al (2009) Kinetics of active and total thymoglobulin in paediatric stem cell transplantation. Bone Marrow Transplant 43:S126–S127

    Google Scholar 

  • Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N (2005) Heterogeneous clearance of antithymocyte globulin after CD34+-selected allogeneic hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant 11:609–618

    PubMed  Google Scholar 

  • Kanda J (2013) Effect of HLA mismatch on acute graft-versus-host disease. Int J Hematol 98:300–308

    CAS  PubMed  Google Scholar 

  • Kanda J, Chiou LW, Szabolcs P et al (2012) Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 18:1664–1676.e1

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DW, Leeder JS, Kauffman RE (2003) Developmental pharmacology—drug disposition, action and therapy in infants and children. New Engl J Med drug Ther 349:1157–1167

    CAS  Google Scholar 

  • Kimland E, Odlind V (2012) Off-label drug use in pediatric patients. Clin Pharmacol Ther 91:796–801

    CAS  PubMed  Google Scholar 

  • Knechtli CJC, Goulden NJ, Hancock JP et al (2014) Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia. Blood 92:4072–4079

    Google Scholar 

  • Knibbe CAJ, Danhof M (2011) Individualized dosing regimens in children based on population PKPD modelling: are we ready for it? Int J Pharm 415:9–14

    CAS  PubMed  Google Scholar 

  • Knibbe CAJ, Krekels EHJ, Danhof M (2011) Advances in paediatric pharmacokinetics. Expert Opin Drug Metab Toxicol 7:1–8

    CAS  PubMed  Google Scholar 

  • Krejci O, van der Velden VHJ, Bader P et al (2003) Level of minimal residual disease prior to haematopoietic stem cell transplantation predicts prognosis in paediatric patients with acute lymphoblastic leukaemia: a report of the Pre-BMT MRD Study Group. Bone Marrow Transplant 32:849–851

    CAS  PubMed  Google Scholar 

  • Krenger W, Blazar BR, Holländer GA (2011) Thymic T-cell development in allogeneic stem cell transplantation. Blood 117:6768–6776

    CAS  PubMed  PubMed Central  Google Scholar 

  • Laínez JM, Orcun S, Pekny JF et al (2014) Comparison of an assumption-free bayesian approach with optimal sampling schedule to a maximum a posteriori approach for personalizing cyclophosphamide dosing. Pharmacotherapy 34:330–335

    PubMed  Google Scholar 

  • Lalmohamed A, Bartelink I, van Reij L et al (2015) Studying the optimal intravenous busulfan exposure in pediatric allogeneic hematopoietic cell transplantation (alloHCT) to improve clinical outcomes: a multicenter study. Biol Blood Marrow Transplant 21:S102–S103

    Google Scholar 

  • Langenhorst JB, Dorlo TPC, van Maarseveen EM et al (2019a) Population pharmacokinetics of fludarabine in children and adults during conditioning prior to allogeneic hematopoietic cell transplantation. Clin Pharmacokinet 58:627–637

    CAS  PubMed  Google Scholar 

  • Langenhorst JB, van Kesteren C, van Maarseveen EM et al (2019b) Fludarabine exposure in the conditioning prior to allogeneic hematopoietic cell transplantation predicts outcomes. Blood Adv 3(14):2179–2187

    Google Scholar 

  • Lankester A, Bierings M, van Wering E et al (2010) Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation. Leukemia 24:1462–1469

    CAS  PubMed  Google Scholar 

  • Leader A, Lishner M, Michaeli J, Revel A (2011) Fertility considerations and preservation in haemato-oncology patients undergoing treatment. Br J Haematol 153:291–308

    PubMed  Google Scholar 

  • Lee DW, Kochenderfer JN, Stetler-Stevenson M et al (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385:517–528

    CAS  PubMed  Google Scholar 

  • Lindemans CA, Chiesa R, Amrolia PJ et al (2014) Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood 123:126–132

    CAS  PubMed  Google Scholar 

  • Lindemans CA, Calafiore M, Mertelsmann AM et al (2015) Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528:560–564

    CAS  PubMed  PubMed Central  Google Scholar 

  • Locatelli F, Lucarelli B, Merli P (2014) Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother 15:23–36

    CAS  PubMed  Google Scholar 

  • Long-Boyle JR, Green KG, Brunstein CG et al (2011) High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant 46:20–26

    CAS  PubMed  Google Scholar 

  • Louis CU, Savoldo B, Dotti G et al (2011) Antitumor activity and long-term fate of chimeric antigen receptor – positive T cells in patients with neuroblastoma. Blood 118:6050–6056

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lucchini G, Perales M-A, Veys P (2015) Immune reconstitution after cord blood transplantation: peculiarities, clinical implications and management strategies. Cytotherapy 17:711–722

    CAS  PubMed  Google Scholar 

  • Lund TC, Liegel J, Bejanyan N et al (2015) Second allogeneic hematopoietic cell transplantation for graft failure: poor outcomes for neutropenic graft failure. Am J Hematol 90:892–896

    PubMed  PubMed Central  Google Scholar 

  • Mank AP, Davies M (2008) Examining low bacterial dietary practice: a survey on low bacterial food. Eur J Oncol Nurs 12:342–348

    PubMed  Google Scholar 

  • Marsh JC, Pearce RM, Koh MBC et al (2014) Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation. Bone Marrow Transplant 49:42–48

    CAS  PubMed  Google Scholar 

  • Maude SL, Frey N, Shaw PA et al (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371:1507–1517

    PubMed  PubMed Central  Google Scholar 

  • McCune JS, Vicini P, Salinger DH et al (2014a) Population pharmacokinetic/dynamic model of lymphosuppression after fludarabine administration. Cancer Chemother Pharmacol 75:67–75. https://doi.org/10.1007/s00280-014-2618-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCune JS, Jacobson P, Wiseman A, Militano O (2014b) Optimizing drug therapy in pediatric SCT: focus on pharmacokinetics. Bone Marrow Transplant 50:1–8

    Google Scholar 

  • Mohty M (2007) Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia 21:1387–1394

    CAS  PubMed  Google Scholar 

  • Mohty M, Malard F, Savani BN (2014) High-dose total body irradiation and myeloablative conditioning before allogeneic stem cell transplantation: time to rethink? Biol Blood Marrow Transplant 21:1–5

    Google Scholar 

  • Molineux G, Pojda Z, Hampson IN, Lord BI, Dexter TM (1990) Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood 76:2153–2158

    CAS  PubMed  Google Scholar 

  • Nagler A, Savani BN, Labopin M et al (2015) Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: A retrospective, multicentre, registry analysis. Lancet Haematol:384–392

    Google Scholar 

  • Nash RA, Antin JH, Karanes C et al (2000) Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 96:2062–2068

    CAS  PubMed  Google Scholar 

  • O’Grady NP, Alexander M, Dellinger EP et al (2002) Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control 30:476–489

    PubMed  Google Scholar 

  • Oshrine BR, Li Y, Teachey DT, Heimall J, Barrett DM, Bunin N (2013) Immunologic recovery in children after alternative donor allogeneic transplantation for hematologic malignancies: comparison of recipients of partially T cell-depleted peripheral blood stem cells and umbilical cord blood. Biol Blood Marrow Transplant 19:1581–1589

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pai S-Y, Logan BR, Griffith LM et al (2014) Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med 371:434–446

    CAS  PubMed  PubMed Central  Google Scholar 

  • Palucka K, Banchereau J (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:38–48

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park M, Lee YH, Lee SH et al (2014) Cytomegalovirus infection in seropositive unrelated cord blood recipients: a study of 349 Korean patients. Ann Hematol 94:481–489

    PubMed  Google Scholar 

  • Parkman R, Cohen G, Carter SL et al (2006) Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation. Biol Blood Marrow Transplant 12:919–927

    PubMed  Google Scholar 

  • Pasquini M, Zhu X (2018) Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR summary slides. Available at https://www.cibmtr.org

  • Passweg JR, Baldomero H, Peters C et al (2014) Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone Marrow Transplant 49:744–750

    PubMed  PubMed Central  Google Scholar 

  • Passweg JR, Labopin M, Cornelissen J et al (2015) Conditioning intensity in middle-aged patients with AML in first CR: No advantage for myeloablative regimens irrespective of the risk group-an observational analysis by the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 50:1063–1068

    CAS  PubMed  Google Scholar 

  • Petersen SL, Ryder LP, Björk P et al (2003) A comparison of T-, B- and NK-cell reconstitution following conventional or nonmyeloablative conditioning and transplantation with bone marrow or peripheral blood stem cells from human leucocyte antigen identical sibling donors. Bone Marrow Transplant 32:65–72

    CAS  PubMed  Google Scholar 

  • Ponce DM, Eapen M, Sparapani R et al (2015) In vivo T-cell depletion with myeloablative regimens on outcomes after cord blood transplantation for acute lymphoblastic leukemia in children. Biol Blood Marrow Transplant 21:2173–2179

    PubMed  PubMed Central  Google Scholar 

  • Porter DL, Levine BL, Kalos M, Bagg A, June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365:725–733

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rambaldi A, Grassi A, Masciulli A et al (2015) Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: An open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 16:1525–1536

    CAS  PubMed  Google Scholar 

  • Ratanatharathorn V, Nash RA, Przepiorka D et al (1998) Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 92:2303–2314

    CAS  PubMed  Google Scholar 

  • Riechmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332:323–327

    CAS  PubMed  Google Scholar 

  • Robinson PD, Lehrnbecher T, Phillips R, Dupuis LL, Sung L (2016) Strategies for empiric management of pediatric fever and neutropenia in patients with cancer and hematopoietic stem-cell transplantation recipients: a systematic review of randomized trials. J Clin Oncol. https://doi.org/10.1200/JCO.2015.65.8591

  • Sayan M, Cassidy RJ, Butker EE et al (2016) Gonadal shielding technique to preserve fertility in male pediatric patients treated with total body irradiation for stem cell transplantation. Bone Marrow Transplant:1–2

    Google Scholar 

  • Sengsayadeth S, Savani BN, Blaise D, Malard F, Nagler A, Mohty M (2015) Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission – a review from the acute leukemia working party of the EBMT. Haematologica 100:859–869

    PubMed  PubMed Central  Google Scholar 

  • Servais S, Lengline E, Porcher R et al (2014) Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20:507–517

    PubMed  Google Scholar 

  • Sheiner L, Beal S (1980) Evaluation of methods for estimating population pharmacokinetics parameters. I. Michaelis-Menten model: routine clinical pharmacokinetic data. J Pharmacokinet Biopharm 8:553–571

    CAS  PubMed  Google Scholar 

  • Sheinerm L (1984) The population approach to pharmacokinetic data analysis: rationale and standard data analysis methods. Drug Metab Rev 15(1–2):153–171

    Google Scholar 

  • Shulman HM, Sullivan KM, Weiden PL et al (1980) Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 69:204–217

    CAS  PubMed  Google Scholar 

  • Soiffer RJ, Lerademacher J, Ho V et al (2011) Impact of immune modulation with anti − T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies Impact of immune modulation with anti – T-cell antibodies on the outcome of reduc. Blood 117:6963–6970

    CAS  PubMed  PubMed Central  Google Scholar 

  • Storek J, Mohty M, Boelens JJ (2015) Rabbit anti–T cell globulin in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 21:959–970

    CAS  PubMed  Google Scholar 

  • Szabolcs P, Niedzwiecki D (2007) Immune reconstitution after unrelated cord blood transplantation. Cytotherapy 9:111–122

    CAS  PubMed  PubMed Central  Google Scholar 

  • Theurich S, Fischmann H, Chakupurakal G et al (2013) Anti-thymocyte globulins for post-transplant graft-versus-host disease prophylaxis-A systematic review and meta-analysis. Crit Rev Oncol Hematol 88:178–186

    PubMed  Google Scholar 

  • Tolar J, Mehta PA, Walters MC (2012) Hematopoietic cell transplantation for nonmalignant disorders. Biol Blood Marrow Transplant 18:S166–S171

    PubMed  Google Scholar 

  • Uberti JP, Agovi M, Tarima S et al (2011) Comparative analysis of BU and CY versus CY and TBI in full intensity unrelated marrow donor transplantation for AML, CML and myelodysplasia. Bone Marrow Transplant 46:34–43

    CAS  PubMed  Google Scholar 

  • Van Kesteren C, Zandvliet AS, Karlsson MO et al (2005) Semi-physiological model describing the hematological toxicity of the anti-cancer agent indisulam. Invest New Drugs 23:225–234

    CAS  PubMed  Google Scholar 

  • Veys P, Wynn RF, Ahn KW et al (2012) Impact of immune modulation with in vivo T cell depletion and myleoablative total body irradiation conditioning regimen on outcomes after unrelated donor transplantation for acute lymphoblastic leukemia in children. Blood 119:6155–6162

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wagner JE, Eapen M, Carter S et al (2014) One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 371:1685–1694

    CAS  PubMed  PubMed Central  Google Scholar 

  • Waller EK, A a L, Lonial S et al (2003) Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant 9:460–471

    CAS  PubMed  Google Scholar 

  • Wang L, Gu Z, Zhai R et al (2015) The efficacy and safety of sirolimus-based graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. Transfusion 55:2134–2141

    CAS  PubMed  Google Scholar 

  • Willemsen L, Jol-van der Zijde CM, Admiraal R et al (2015) Impact of serotherapy on immune reconstitution and survival outcomes after stem cell transplantations in children: thymoglobulin versus alemtuzumab. Biol Blood Marrow Transplant 21:473–482

    CAS  PubMed  Google Scholar 

  • Williams K, Hakim FT, Gress RE (2008) T-cell immune reconstitution following lymphodepletion. Semin Immunol 19:318–330

    Google Scholar 

  • Zhou X, Di Stasi A, Tey S-K et al (2014) Long-term outcome and immune reconstitution after haploidentical stem cell transplant in recipients of allodepleted-T-cells expressing the inducible caspase-9 safety transgene. Blood 123(25):3895–3905. https://doi.org/10.1182/blood-2014-01-551671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blood and Marrow Transplantation Program, Prinses Maxima Center for Pediatric Oncology, Utrecht, The Netherlands

    R. Admiraal

  2. Stem Cell Transplantation and Cellular Therapies Pediatrics, New York, NY, USA

    J. J. Boelens

  3. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    J. J. Boelens

Authors
  1. R. Admiraal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. J. Boelens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. J. Boelens .

Editor information

Editors and Affiliations

  1. Hospital for Children and Adolescents Center of Paediatric Research Department of Women and Child Health, University of Leipzig, Leipzig, Germany

    Wieland Kiess

  2. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Department of Clinical Pharmacology, University Hospital Tüebingen, Tüebingen, Germany, Robert Bosch Gesellschaft fuer medizinische Forschung mbH, Stuttgart, Germany

    Matthias Schwab

  3. Children’s Hospital, University of Basel Children’s Hospital, Basel, Switzerland

    Johannes van den Anker

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Admiraal, R., Boelens, J.J. (2019). Pharmacotherapy in Pediatric Hematopoietic Cell Transplantation. In: Kiess, W., Schwab, M., van den Anker, J. (eds) Pediatric Pharmacotherapy . Handbook of Experimental Pharmacology, vol 261. Springer, Cham. https://doi.org/10.1007/164_2019_247

Download citation

Publish with us

Policies and ethics

Search

Navigation