How adoptive transfer of components of the donor immune system boosts GvL and prevents GvHD in HLA-haploidentical hematopoietic transplantation for acute leukemia

Appelbaum FR, Forman SJ, Negrin RS, Blume KG (eds). Thomas’ Hematopoietic Cell Transplantation. 4th ed. Wiley-Blackwell, Oxford, 2009.

Anasetti C, Aversa F, Velardi A. Hematopoietic cell transplantation from human leukocyte antigen partially matched related donors. In: Appelbaum FR, Forman SJ, Negrin RS, Blume KG (eds). Thomas’ Hematopoietic Cell Transplantation. 4th ed. Wiley-Blackwell, Oxford, 2009. pp 657-74.

Mancusi A, Ruggeri L, Velardi A. Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood. 2016;128:2616–23. https://doi.org/10.1182/blood-2016-07-730564.

Article  CAS  PubMed  Google Scholar 

Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:132. https://doi.org/10.1038/nrclinonc.2015.128.

Article  CAS  PubMed  Google Scholar 

O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2002;8:377–86. https://doi.org/10.1053/bbmt.2002.v8.pm12171484.

Article  Google Scholar 

Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14:641–50. https://doi.org/10.1016/j.bbmt.2008.03.005.

Article  CAS  Google Scholar 

McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolaños-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–31. https://doi.org/10.1182/blood-2015-01-623991.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40. https://doi.org/10.1182/blood-2015-04-639831.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Solomon SR, St Martin A, Shah NN, Fatobene G, Al Malki MM, Ballen KK, et al. Myeloablative vs reduced intensity T-cell-replete haploidentical transplantation for hematologic malignancy. Blood Adv. 2019;3:2836–44. https://doi.org/10.1182/bloodadvances.2019000627.

Article  PubMed  PubMed Central  Google Scholar 

Gooptu M, Romee R, St Martin A, Arora M, Al Malki M, Antin JH, et al. HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis. Blood. 2021;138:273–82. https://doi.org/10.1182/blood.2021011281.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Raiola AM, Angelucci E, Sica S, Bacigalupo A. Haploidentical bone marrow transplants with post transplant cyclophosphamide on day + 3 + 5: The Genova protocol. Blood Rev. 2022;62:101031. https://doi.org/10.1016/j.blre.2022.101031.

Article  CAS  PubMed  Google Scholar 

Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, et al. 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. 1998;339:1186–93. https://doi.org/10.1056/NEJM199810223391702.

Article  CAS  PubMed  Google Scholar 

Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–54. https://doi.org/10.1200/JCO.2005.09.117.

Article  PubMed  Google Scholar 

Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, et al. Acute Leukemia Working Party (ALWP) of European Blood and Marrow Transplant (EBMT) Group. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008;112:3574–81. https://doi.org/10.1182/blood-2008-02-140095.

Article  CAS  PubMed  Google Scholar 

Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood. 1999;94:333–9. https://doi.org/10.1182/blood.V94.1.333.413a31_333_339.

Article  CAS  PubMed  Google Scholar 

Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100. https://doi.org/10.1126/science.1068440.

Article  CAS  PubMed  Google Scholar 

Kärre K. Immunology. A perfect mismatch. Science. 2002;295:2029–31. https://doi.org/10.1126/science.1070538.

Article  PubMed  Google Scholar 

Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110:433–40. https://doi.org/10.1182/blood-2006-07-038687.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Velardi A, Ruggeri L, Mancusi A, Aversa F, Christiansen FT. Natural killer cell allorecognition of missing self in allogeneic hematopoietic transplantation: a tool for immunotherapy of leukemia. Curr Opin Immunol. 2009;21:525–30. https://doi.org/10.1016/j.coi.2009.07.015.

Article  CAS  PubMed  Google Scholar 

Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44–49. https://doi.org/10.1126/science.1198687.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005;5:201–14. https://doi.org/10.1038/nri1570.

Article  CAS  PubMed  Google Scholar 

Kärre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986;319:675–8. https://doi.org/10.1038/319675a0.

Article  PubMed  Google Scholar 

Colonna M, Brooks EG, Falco M, Ferrara GB, Strominger JL. Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science. 1993;260:1121–4. https://doi.org/10.1126/science.8493555.

Article  CAS  PubMed  Google Scholar 

Haas P, Loiseau P, Tamouza R, Cayuela JM, Moins-Teisserenc H, Busson M, et al. NK-cell education is shaped by donor HLA genotype after unrelated allogeneic hematopoietic stem cell transplantation. Blood. 2011;117:1021–9. https://doi.org/10.1182/blood-2010-02-269381.

Article  CAS  PubMed  Google Scholar 

Leung W, Iyengar R, Turner V, Lang P, Bader P, Conn P, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172:644–50. https://doi.org/10.4049/jimmunol.172.1.644.

Article  CAS  PubMed  Google Scholar 

Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50. https://doi.org/10.1038/nm915.

Article  CAS  PubMed  Google Scholar 

Martelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, et al. HLA-haploidentical transplantation with regulatory and conventional T cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124:638–44. https://doi.org/10.1182/blood-2014-03-564401.

Article  CAS  PubMed  Google Scholar 

Booth NJ, McQuaid AJ, Sobande T, Kissane S, Agius E, Jackson SE, et al. Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J Immunol. 2010;184:4317–26. https://doi.org/10.4049/jimmunol.0903781.

Article  CAS  PubMed  Google Scholar 

Ruggeri L, Carotti A, Pierini A, Falzetti F, Terenzi A, Urbani E, et al. How adoptive immunotherapy with conventional T and regulatory T cells exerts a Gvl effect without GvHD, after haploidentical hematopoietic transplantation. Blood. 2018;132:3333. https://doi.org/10.1182/blood-2018-99-112512.

Article  Google Scholar 

Pierini A, Ruggeri L, Carotti A, Falzetti F, Saldi S, Terenzi A, et al. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia. Blood Adv. 2021;5:1199–208. https://doi.org/10.1182/bloodadvances.2020003739.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wong JY, Liu A, Schultheiss T, Popplewell L, Stein A, Rosenthal J, et al. Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. Biol Blood Marrow Transpl. 2006;12:306–15. https://doi.org/10.1016/j.bbmt.2005.10.026.

Article  Google Scholar 

Rosenthal J, Wong J, Stein A, Qian D, Hitt D, Naeem H, et al. Phase 1/2 trial of total marrow and lymph node irradiation to augment reduced-intensity transplantation for advanced hematologic malignancies. Blood. 2011;117:309–15. https://doi.org/10.1182/blood-2010-06-288357.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jensen LG, Stiller T, Wong JYC, Palmer J, Stein A, Rosenthal J. Total marrow lymphoid irradiation/fludarabine/melphalan conditioning for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2018;24:301–7. https://doi.org/10.1016/j.bbmt.2017.09.019.

Article  CAS  Google Scholar 

Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117:3921–8. https://doi.org/10.1182/blood-2010-10-

Comments (0)

No login
gif