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The Future of Transplantation: Hope, Investigative Discipline, and Fairness

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Contemporary Bone Marrow Transplantation

Part of the book series: Organ and Tissue Transplantation ((OTT))

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Abstract

Hematopoietic cell transplantation has improved over its more than five decades of experience bringing new opportunities for treatment to many thousands of patients. With advances in donor options, graft sources, and improved understanding of factors controlling the risks of relapse, allogeneic transplantation can be disease controlling or curative for patients with life-threatening malignant, immunologic, or hematologic disorders. Limiting transplant toxicities through better understanding the pathophysiology of acute and chronic disease graft-versus-host disease as well as other early and late toxicities has also limited the morbidity and mortality of the procedure. Its complexity including requirement for multidisciplinary expertise, extensive transfusions, and novel pharmaceutical support has also increased its costs, thereby creating additional barriers for many patients throughout the world. Ongoing research and quality improvements are continuing to advance transplant approaches and helping many more patients enjoy its benefits, even as competing novel cell therapeutics may offer alternatives to allogeneic transplants.

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References

  • Anasetti C, Logan BR, Lee SJ et al (2012) Peripheral blood stem cells versus bone marrow from unrelated donors. N Engl J Med 367:1487–1496

    Article  CAS  PubMed  Google Scholar 

  • Andermann T, Peled J, Ho C et al (2018) The microbiome and hematopoietic cell transplantation: past, present, and future on behalf of the blood and marrow transplant clinical trials network. Biol Blood Marrow Transplant 24:1322–1340

    Google Scholar 

  • Aversa F, Terenzi A, Tabilio A et al (2005) Full haplotypemismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 23:3447–3454

    Article  PubMed  Google Scholar 

  • Bacigalupo A, Ballen K, Rizzo D et al (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15(12):1628–1633

    Article  PubMed  PubMed Central  Google Scholar 

  • Blaise D, Kuentz M, Fortanier C et al (2000) Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the soeiete francaise de greffe de moelle. J Clin Oncol 18:537–546

    Article  CAS  PubMed  Google Scholar 

  • Brunstein CG, Fuchs EJ, Carter SL et al (2011a) Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 18:282–288

    Article  CAS  Google Scholar 

  • Brunstein CG, Miller JS, Cao Q et al (2011b) Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 117:1061–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang YJ, Huang XJ (2019) Is human leukocyte antigen-matched sibling donor transplant always better +-than haploidentical allograft? Semin Hematol 56(3):201–208

    Google Scholar 

  • Cichocki F, Taras E, Chiuppesi F et al (2019) Adaptive NK cell reconstitution is associated with better clinical outcomes. JCI Insight. 2019 Jan 24;4(2):e125553. https://doi.org/10.1172/jci.insight.125553. Online ahead of print.PMID: 30674718

  • Ciurea SO, Lee DA, Cao K et al (2015a) Phase I trial of IL-21 ex vivo expanded NK cells administration to prevent disease relapse after haploidentical stem-cell transplantation for myeloid leukemias. Blood 126:102

    Article  Google Scholar 

  • Ciurea SO, Zhang M-J, Bacigalupo A et al (2015b) Haploidentical transplant with post-transplant cyclophosphamide versus matched unrelated donor transplant for acute myeloid leukemia. Blood 126:1033–1040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cutler C, Giri S, Jeyapalan S et al (2001) Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 19:3685–3691

    Article  CAS  PubMed  Google Scholar 

  • El Fakih R, Hashmi SK, Ciurea SO, Luznik L, Gale RP, Aljurf M (2020) Post-transplant cyclophosphamide use in matched HLA donors: a review of literature and future application. Bone Marrow Transplant 55(1):40–47

    Google Scholar 

  • Fesnak AD, June CH, Levine BL (2016) Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer 16(9):566–581. https://doi.org/10.1038/nrc.2016.97. Review. PubMed PMID: 27550819; PubMed Central PMCID: PMC5543811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garfall AL, Stadtmauer EA, Hwang WT, Lacey SF, Melenhorst JJ, Krevvata M, Carroll MP, Matsui WH, Wang Q, Dhodapkar MV, Dhodapkar K, Das R, Vogl DT, Weiss BM, Cohen AD, Mangan PA, Ayers EC, Nunez-Cruz S, Kulikovskaya I, Davis MM, Lamontagne A, Dengel K, Kerr ND, Young RM, Siegel DL, Levine BL, Milone MC, Maus MV, June CH. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight. 2018;3(8). pii: 120505. https://doi.org/10.1172/jci.insight.120505. eCollection 2018 Apr 19. Erratum in: JCI Insight. 2019 Feb 21;4(4):. PubMed PMID: 29669947; PubMed Central PMCID: PMC5931130

  • Gragert L, Eapen M, Williams E et al (2014) HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 371:339–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He X, Feng Z, Ma J, Ling S, Cao Y, Gurung B, Wu Y, Katona BW, O'Dwyer KP, Siegel DL, June CH, Hua X (2020) Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia. Blood 135(10):713–723. https://doi.org/10.1182/blood.2019002779. PubMed PMID: 31951650; PubMed Central PMCID: PMC7059518

    Article  PubMed  PubMed Central  Google Scholar 

  • Hobbs JR, Hugh-Jones K, Barrett AJ et al (1981) Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 2(8249):709–712

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann P, Ermann J, Edinger M et al (2002) Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 196:389–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • June CH, O'Connor RS, Kawalekar OU, Ghassemi S, Milone MC (2018) CAR T cell immunotherapy for human cancer. Science 359(6382):1361–1365. https://doi.org/10.1126/science.aar6711. Review

    Article  CAS  PubMed  Google Scholar 

  • Khera N, Emmert A, Storer BE et al (2014) Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens. Oncologist 19:639–644

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolb HJ, Mittermuller J, Clemm C et al (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76:2462–2465

    Article  CAS  PubMed  Google Scholar 

  • Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K (2020) Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med 382(6):545–553. https://doi.org/10.1056/NEJMoa1910607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lucarelli G, Polchi P, Izzi T et al (1985) Marrow transplantation for thalassemia after treatment with busulfan and cyclophosphamide. Ann N Y Acad Sci 445:428–431

    Article  CAS  PubMed  Google Scholar 

  • Majhail NS, Rizzo JD (2013) Surviving the cure: long term followup of hematopoietic cell transplant recipients. Bone Marrow Transplant 48:1145–1151

    Article  CAS  PubMed  Google Scholar 

  • Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA (2018) Tisagenlecleucel in children and Young adults with B-cell lymphoblastic leukemia. N Engl J Med 378(5):439–448. https://doi.org/10.1056/NEJMoa1709866. PubMed PMID: 29385370; PubMed Central PMCID: PMC5996391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maung K, Horwitz M (2019) Current and future perspectives on allogeneic transplantation using ex vivo expansion or manipulation of umbilical cord blood cells. Int J Hematol 110(1):50–58

    Article  PubMed  Google Scholar 

  • McCurdy SR, Kanakry JA, Showel MM et al (2015) Risk-stratified outcomes of nonmyeloablative, HLA-haploidentical BMT with high dose post transplantation cyclophosphamide. Blood 125:3024–3031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCurdy SR, Zhang M-J, St Martin A et al (2018) Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide. Blood Adv 2(3):299–307

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller JS, Soignier Y, Panoskaltsis-Mortari A et al (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105:3051–3057

    Article  CAS  PubMed  Google Scholar 

  • Miller JS, Rooney CM, Curtsinger J et al (2014) Expansion and homing of adoptively transferred human natural killer cells in immunodeficient mice varies with product preparation and in vivo cytokine administration: implications for clinical therapy. Biol. Blood Marrow Transplant 20:1252–1257

    Article  CAS  Google Scholar 

  • Parody R, Martino R, de la Cámara R et al (2014) Fungal and viral infections after allogeneic hematopoietic transplantation from unrelated donors in adults: improving outcomes over time. Bone Marrow Transplant 50:274–281

    Article  PubMed  Google Scholar 

  • Pillai V, Muralidharan K, Meng W, Bagashev A, Oldridge DA, Rosenthal J, Van Arnam J, Melenhorst JJ, Mohan D, DiNofia AM, Luo M, Cherian S, Fromm JR, Wertheim G, Thomas-Tikhonenko A, Paessler M, June CH, Luning Prak ET, Bhoj VG, Grupp SA, Maude SL, Rheingold SR (2019) CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Adv 3(22):3539–3549. https://doi.org/10.1182/bloodadvances.2019000692. PubMed PMID: 31738832; PubMed Central PMCID: PMC6880911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rashidi A, Hamadani M, Zhang MJ et al (2019) Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv 3(12):1826–1836

    Article  PubMed  PubMed Central  Google Scholar 

  • Rezvani K, Rouce R, Liu E et al (2017) Engineering natural killer cells for cancer immunotherapy. Mol Ther 25(8):1769–1781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ricci A, Jin Z, Bourgeois W et al (2018) Health care utilization and cost of allogeneic hematopoietic cell transplantation (alloHCT) in children with malignant and nonmalignant diseases. Biol Blood Marrow Transplant 24(3 Suppl):S427

    Article  Google Scholar 

  • Rosenberg AR, Syrjala KL, Martin PJ et al (2015) Resilience, health, and quality of life among longterm survivors of hematopoietic cell transplantation. Cancer 121(23):42507

    Article  Google Scholar 

  • Roy D, Maertens J, Walker I et al (2014) Selective photodepletion of recipient-alloreactive T-cells enables safe and efficacious haploidentical HSCT: initial results from a phase 2 trial in patients with AML, ALL, and MDS. Blood 124:314

    Article  Google Scholar 

  • Rubenstein P, Carrier C, Scaradavou A et al (1998) Outcomes among 562 recipients of placentalblood transplants from unrelated donors. N Engl J Med 339:156577

    Google Scholar 

  • Ruggeri A, Labopin M, Sanz G et al (2015) Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia 29:1891–1900

    Article  CAS  PubMed  Google Scholar 

  • Schmitz N, Eapen M, Horowitz MM et al (2006) Long-term outcome of patients given transplants of mobilized blood or bone marrow: a report from the international bone marrow transplant registry and the European Group for Blood and Marrow Transplantation. Blood 108:4288–4290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorror ML (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106:2912–2919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, Mangan PA, Kulikovskaya I, Gupta M, Chen F, Tian L, Gonzalez VE, Xu J, Jung IY, Melenhorst JJ, Plesa G, Shea J, Matlawski T, Cervini A, Gaymon AL, Desjardins S, Lamontagne A, Salas-Mckee J, Fesnak A, Siegel DL, Levine BL, Jadlowsky JK, Young RM, Chew A, Hwang WT, Hexner EO, Carreno BM, Nobles CL, Bushman FD, Parker KR, Qi Y, Satpathy AT, Chang HY, Zhao Y, Lacey SF, June CH. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481). pii: eaba7365. https://doi.org/10.1126/science.aba7365. Epub 2020 Feb 6

  • Sullivan KM, Goldmuntz EA, Keyes-Elstein L et al (2018) Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med 378(1):35–47

    Article  PubMed  PubMed Central  Google Scholar 

  • Sutton R, Shaw PJ, Venn NC et al (2014) Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia. Br J Haematol 168(3):395–404

    Article  PubMed  Google Scholar 

  • Taur Y, Jenq RR, Perales M-A et al (2014) The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124(7):1174–1182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Topp MS, Gökbuget N, Zugmaier G et al (2012) Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 120:5185–5187

    Article  CAS  PubMed  Google Scholar 

  • van den Brink MRM, Velardi E, Perales M-A (2015) Immune reconstitution following stem cell transplantation. Hematology 2015(1):215–219

    Article  PubMed  Google Scholar 

  • van Rood JJ, Goldman JM (2010) Future perspectives. Bone Marrow Transplant 45:843–845

    Article  PubMed  Google Scholar 

  • Yan CH, Liu QF, Wu DP et al (2017) Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 23(8):1311–1319

    Article  PubMed  Google Scholar 

  • Yeshurun M, Weisdorf D, Rowe JM et al (2019) The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Adv 3(4):670–680

    Article  PubMed  PubMed Central  Google Scholar 

  • Zeiser R, Blazar BR (2017a) Acute graft-versus-host disease - biologic process, prevention, and therapy. N Engl J Med 377(22):2167–2179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeiser R, Blazar BR (2017b) Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med 377(26):2565–2579

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. University of Minnesota, Minneapolis, MN, USA

    Daniel Weisdorf

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  1. Daniel Weisdorf
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Correspondence to Daniel Weisdorf .

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Editors and Affiliations

  1. Clinical Hematology Oncology and Hematopoietic Cell Transplantation, Tata Medical Center, Kolkata, India

    Mammen Chandy

  2. Clinical Hematology Oncology and Hematopoietic Cell Transplantation, Tata Medical Center, Kolkata, India

    Vivek S. Radhakrishnan

  3. Department of Pediatric Hematology-Oncology, Tata Medical Center, Kolkata, India

    Reghu K. Sukumaran

Section Editor information

  1. Tata Medical Center, Kolkata, India

    Vivek Radhakrishnan

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Weisdorf, D. (2021). The Future of Transplantation: Hope, Investigative Discipline, and Fairness. In: Chandy, M., Radhakrishnan, V.S., Sukumaran, R.K. (eds) Contemporary Bone Marrow Transplantation. Organ and Tissue Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-030-36358-1_2

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  • DOI: https://doi.org/10.1007/978-3-030-36358-1_2

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-030-36358-1

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