Skip to main content
SpringerLink
Log in

Allogeneic Haematopoietic Stem Cell Transplantation and Natural Killer Cell Alloreactivity

  • Chapter
  • First Online:
Allogeneic Stem Cell Transplantation

Part of the book series: Contemporary Hematology ((CH))

  • 1421 Accesses

Abstract

Despite advances in chemotherapy, most adults with acute lymphoblastic leukemia (ALL) or Acute Myeloid Leukemia (AML) relapse and few survive when they have unfavorable cytogenetics at diagnosis, when they do not achieve complete remission (CR) after the first induction cycle and when they are in second or later remission [1-3].

Under these circumstances, an allogeneic hematopoietic stem cell transplant (HSCT) is preferred as post-remission therapy [4-6]. As only 30% of patients have a matched sibling donor, the only option is transplantation from an alternative donor.

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 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  1. Byrd JC, Mrozek K, Dodge RK et al (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100:4325-4336

    Article  PubMed  CAS  Google Scholar 

  2. Giles FJ, Keating A, Goldstone AH, Avivi I, Willman CL, Kantarjian HM (2002) Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program) 73-110

    Google Scholar 

  3. Hoelzer D, Gokbuget N, Ottmann O, et al (2002) Acute lymphoblastic leukemia. Hematology (Am Soc Hematol Educ Program) 162-192

    Google Scholar 

  4. Burnett AK, Wheatley K, Goldstone AH et al (2002) The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 118:385-400

    Article  PubMed  Google Scholar 

  5. Tavernier E, Le QH, Elhamri M, Thomas X (2003) Salvage therapy in refractory acute myeloid leukemia: prediction of outcome based on analysis of prognostic factors. Leuk Res 27:205-214

    Article  PubMed  CAS  Google Scholar 

  6. Litzow MR (2007) Progress and strategies for patients with relapsed and refractory acute myeloid leukemia. Curr Opin Hematol 14(2):130-137

    Google Scholar 

  7. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, Fernandez-Vina M, Flomenberg N, Horowitz M, Hurley CK, Noreen H, Oudshoorn M, Petersdorf E, Setterholm M, Spellman S, Weisdorf D, Williams TM, Anasetti C (2007) High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 110(13):4576-4583

    Article  PubMed  CAS  Google Scholar 

  8. Perz JB, Szydlo R, Sergeant R, Sanz J, O’Shea D, Khan T, Davey N, Loaiza S, Davis J, Apperley JF, Olavarria E (2007) Impact of HLA class I and class II DNA high-resolution HLA typing on clinical outcome in adult unrelated stem cell transplantation after in vivo T-cell depletion with alemtuzumab. Transpl Immunol 18(2):179-185

    Article  PubMed  CAS  Google Scholar 

  9. Madrigal A, Shaw BE (2008) Immunogenetic factors in donors and patients that affect the outcome of hematopoietic stem cell transplantation. Blood Cells Mol Dis 40(1):40-43

    Article  PubMed  CAS  Google Scholar 

  10. Takahashi S (2007) Leukemia: cord blood for allogeneic stem cell transplantation. Curr Opin Oncol 19(6):667-672 Review

    Article  PubMed  Google Scholar 

  11. Sanz MA, Sanz GF (2002) Unrelated donor umbelical cord blood transplantation in adults. Leukemia 16:1984-1991

    Article  PubMed  CAS  Google Scholar 

  12. Rocha V, Labopin M, Sanz G et al (2004) Transplants of umbilical cord blood or bone marrow from unrelated donors in adult with leukemia. N Engl J Med 351:2276-2285

    Article  PubMed  CAS  Google Scholar 

  13. Brunstein CG, Setubal DC, Wagner JE (2007) Expanding the role of umbilical cord blood transplantation. Br J Haematol 137(1):20-35

    PubMed  Google Scholar 

  14. Ruggeri L, Capanni M, Casucci M et al (1999) Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 94:333-339

    PubMed  CAS  Google Scholar 

  15. Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097-2100

    Article  PubMed  CAS  Google Scholar 

  16. Velardi A, Ruggeri L, Moretta A, Moretta L (2002) NK cells: a lesson from mismatched hematopoietic transplantation. Trends Immunol 23:438-444

    Article  PubMed  CAS  Google Scholar 

  17. Ruggeri L, Aversa F, Martelli MF, Velardi A (2006) Haploidentical transplantation and natural killer cell recognition of missing self. Immunol Rev 214:202-218

    Article  PubMed  CAS  Google Scholar 

  18. Ruggeri L, Mancusi A, Burchielli E, Aversa F, Martelli MF, Velardi A (2007) Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. Curr Opin Oncol 19(2):142-147

    Article  PubMed  Google Scholar 

  19. Moretta L, Moretta A (2004) Killer immunoglobulin-like receptors. Curr Opin Immunol 16:626-633

    Article  PubMed  CAS  Google Scholar 

  20. Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201-214

    Article  PubMed  CAS  Google Scholar 

  21. Yawata M, Yawata N, Draghi M, Little AM, Parteniou F, Parham P (2006) Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. J Exp Med 203:633-645

    Article  PubMed  CAS  Google Scholar 

  22. Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T et al (2007) Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 110:433-440

    Article  PubMed  CAS  Google Scholar 

  23. Mickelson EM, Petersdorf EW, Hansen JA (2002) HLA matching and hematopoietic cell transplant outcome. Clin Transpl 263-271

    Google Scholar 

  24. Terenzi A, Aversa F, Albi N, Galandrini R, Dembech C, Velardi A, Martelli MF (1993) Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs. Bone Marrow Transplant 11:357-361

    PubMed  CAS  Google Scholar 

  25. Reisner Y, Kapoor N, Kirkpatrick D et al (1983) Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61:341-348

    PubMed  CAS  Google Scholar 

  26. Bachar-Lusting E, Rachamim N, Li HW et al (1995) Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice. Nat Med 1:1268-1273

    Article  Google Scholar 

  27. Rachamin N, Gan J, Segall R et al (1998) Tolerance induction by “megadose” hematopoietic transplants: donor-type human CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T lymphocyte precursors in mixed lymphocyte culture. Transplantation 65:1386-1393

    Article  Google Scholar 

  28. Gur H, Krauthgamer R, Berrebi A et al (2002) Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34(+) cells. Blood 99:4174-4181

    Article  PubMed  CAS  Google Scholar 

  29. Gur H, Krauthgamer R, Bachar-Lustig E, Katchman H, Arbel-Goren R, Berrebi A et al (2005) Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion-based mechanism mediated by TNF-alpha. Blood 105(6):2585-2593

    Article  PubMed  CAS  Google Scholar 

  30. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C et al (1994) Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 84:3948-3955

    PubMed  CAS  Google Scholar 

  31. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al (1998) Treatment of high risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 339:1186-1193

    Article  PubMed  CAS  Google Scholar 

  32. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S et al (2005) Full-haplotype mismatched hematopoietic stem cell transplantation: a phase II study in patients with acute leukemia at high risk or relapse. J Clin Oncol 23:3447-3454

    Article  PubMed  Google Scholar 

  33. Liu D, Tammik C, Zou JZ, Ernberg I, Masucci MG, Ringden O, Levitsky V (2004) Effect of combined T- and B-cell depletion of allogeneic HLA-mismatched bone marrow graft on the magnitude and kinetics of Epstein-Barr virus load in the peripheral blood of bone marrow transplant recipients. Clin Transplant 18(5):518-524

    Article  PubMed  Google Scholar 

  34. Terenzi A, Aristei C, Aversa F et al (1996) Efficacy of fludarabine as an immunosuppressor for bone marrow transplantation conditioning: preliminary results. Transplant Proc 28:3101

    PubMed  CAS  Google Scholar 

  35. Volpi I, Perruccio K, Tosti A et al (2001) Post-grafting granulocyte colony-stimulating factor administration impairs functional immune recovery in recipients of HLA haplotype-mismatched hematopoietic transplants. Blood 97:2514-2521

    Article  PubMed  CAS  Google Scholar 

  36. Russell JA, Turner AR, Larratt L, Chaudhry A, Morris D, Brown C et al (2007) Adult recipients of matched related donor blood cell transplants given myeloablative regimens including pretransplant antithymocyte globulin have lower mortality related to graft-versus-host disease: a matched pair analysis. Biol Blood Marrow Transplant 13(3):299-306

    Article  PubMed  CAS  Google Scholar 

  37. Waller EK, Langston AA, Lonial S, Cherry J, Somani J, Allen AJ 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(7):460-471

    Article  PubMed  CAS  Google Scholar 

  38. Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L, Carotti A et al (2005) Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 106:4397-4406

    Article  PubMed  CAS  Google Scholar 

  39. Liu Z, Savoldo B, Huls H et al (2002) Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomas. Recent Results Cancer Res 159:123-133

    PubMed  CAS  Google Scholar 

  40. Comoli P, Basso S, Zecca M, Pagliara D, Baldanti F, Bernardo ME et al (2007) Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am J Transplant 7(6):1648-1655

    Article  PubMed  CAS  Google Scholar 

  41. Marktel S, Magnani Z, Ciceri F, Cazzaniga S, Riddell SR, Traversari C et al (2003) Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation. Blood 101(4):1290-1298

    Article  PubMed  CAS  Google Scholar 

  42. Ciceri F, Bonini C, Gallo-Stampino C, Bordignon C (2005) Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation. Cytotherapy 7(2):144-149

    Article  PubMed  CAS  Google Scholar 

  43. Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F et al (2007) The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood 109(11):4708-4715

    Article  PubMed  CAS  Google Scholar 

  44. Hwang WYK, Samuel M, Tan D et al (2007) A meta-Analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Bone Marrow Transplant 13:444-453

    Article  Google Scholar 

  45. Smith HRC, Heusel JW, Mehta IK et al (2002) Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 99:8826-8831

    PubMed  CAS  Google Scholar 

  46. Martin MP et al (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31:429-434

    PubMed  CAS  Google Scholar 

  47. Guma M et al (2004) Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood 104:3664-3671

    Article  PubMed  CAS  Google Scholar 

  48. Degli Esposti MA, Smyth MJ (2005) Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5:112-124

    Article  PubMed  CAS  Google Scholar 

  49. Davies SM, Ruggieri L, DeFor T et al (2002) Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Blood 100:3825-3827

    Article  PubMed  CAS  Google Scholar 

  50. Farag SS, Bacigalupo A, Eapen M et al (2006) The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: a report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and the Dutch registry. Biol Blood Marrow Transplant 12:876-884

    Article  PubMed  CAS  Google Scholar 

  51. Cooley S, McCullar V, Wangen R et al (2005) KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation. Blood 106:4370-4376

    Article  PubMed  CAS  Google Scholar 

  52. Giebel S, Locatelli F, Lamparelli T et al (2003) Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 102:814-819

    Article  PubMed  CAS  Google Scholar 

  53. Elmaagacli AH, Ottinger H, Koldehoff M et al (2005) Reduced risk for molecular disease in patients with chronic myeloid leukemia after transplantation from a KIR-mismatched donor. Transplantation 79:1741-1747

    Article  PubMed  CAS  Google Scholar 

  54. Beelen DW, Hottinger HD, Ferencic S et al (2005) Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias. Blood 105:2594-2600

    Article  PubMed  CAS  Google Scholar 

  55. Dawson MA, Spencer A (2005) Successful use of haploidentical stem-cell transplantation with KIR mismatch as initial therapy for poor-risk myelodysplastic syndrome. J Clin Oncol 23:4473-4474

    Article  PubMed  Google Scholar 

  56. Willemze R, Arrais Rodrigues C, Labopin M, et al (2008) Inhibitory KIR-ligend mismatching is associated with decreased incidence of relapse and improved disease-free survival after unrelated cord blood stem cell transplantation for patients with acute leukaemia. Bone Marrow Transplant 41(suppl 1); Abstr 83

    Google Scholar 

  57. Leung W, Iyengar R, Turner V et al (2004) Determinants of antileukemia effects of allogeneic NK cells. J Immunol 172:644-650

    PubMed  CAS  Google Scholar 

  58. Hsu KC, Keever-Taylor CA, Wilton A et al (2005) Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 105:4878-4884

    Article  PubMed  CAS  Google Scholar 

  59. Hsu KC, Gooley T, Malkki M et al (2006) KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy. Biol Blood Marrow Transpl 12:828-836

    Article  CAS  Google Scholar 

  60. Fernandez NC, Treiner E, Vance RE, Jamieson AM, Lemieux S, Raulet DH (2005) A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105:4416-4423

    Article  PubMed  CAS  Google Scholar 

  61. Pando MJ, Gardiner CM, Gleimer M, McQueen KL, Parham P (2003) The protein made from a common allele of KIR3DL1 (3DL*004) is poorly expressed at cell surfaces due to substitution at position 86 in Ig domain 0 and 182 in Ig domain 1. J Immunol 171:6640-6647

    PubMed  CAS  Google Scholar 

  62. Dey BR, Spitzer TR (2006) Current status of haploidentical stem cell transplantation. Br J Haematol 135(4):423-437

    Article  PubMed  Google Scholar 

  63. Zorn E (2006) CD4 + CD25+ regulatory T cells in human hematopoietic cell transplantation. Semin Cancer Biol 16(2):150-159

    Article  PubMed  CAS  Google Scholar 

  64. Le Blanc K, Ringden O (2006) Mesenchymal stem cells: properties and role in clinical bone marrow transplantation. Curr Opin Immunol 18(5):586-591

    Article  PubMed  Google Scholar 

  65. Schattenberg AV, Dolstra H (2005) Cellular adoptive immunotherapy after allogeneic stem cell transplantation. Curr Opin Oncol 17(6):617-621

    Article  PubMed  Google Scholar 

  66. Peggs KS, Verfuerth S, Pizzey A, Khan N, Guiver M, Moss PA, Mackinnon S (2003) Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet 362:1375-1377

    Article  PubMed  Google Scholar 

  67. Einsele H, Hebart H (2004) CMV-specific immunotherapy. Hum Immunol 65(5):558-564

    Article  PubMed  CAS  Google Scholar 

  68. Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K et al (2006) Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 134:64-76

    Article  PubMed  Google Scholar 

  69. Thorne SH, Negrin RS, Contag CH (2006) Synergistic antitumor effects of immune cell-viral biotherapy. Science 311:1780-1784

    Article  PubMed  CAS  Google Scholar 

  70. Seggewiss R, Einsele H (2007) Hematopoietic growth factors including keratinocyte growth factor in allogeneic and autologous stem cell transplantation. Semin Hematol 44(3):203-211

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Haematology and Clinical Immunology, Department of Clinical and Experimental Medicine, HSCT Unit, University of Perugia, Perugia, Italy

    Franco Aversa & Andrea Velardi

Authors
  1. Franco Aversa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Velardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University Hospitals Case Medical Center, Cleveland, OH, USA

    Hillard M. Lazarus

  2. Case Western Reserve University, Cleveland, OH, USA

    Mary J. Laughlin

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Aversa, F., Velardi, A. (2010). Allogeneic Haematopoietic Stem Cell Transplantation and Natural Killer Cell Alloreactivity. In: Lazarus, H.M., Laughlin, M.J. (eds) Allogeneic Stem Cell Transplantation. Contemporary Hematology. Humana Press. https://doi.org/10.1007/978-1-59745-478-0_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-478-0_26

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-33-6

  • Online ISBN: 978-1-59745-478-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation