1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 70, 2019
  5. Article

Annual Review of Medicine

Volume 70, 2019

Expanding Therapeutic Opportunities for Hematopoietic Stem Cell Transplantation: T Cell Depletion as a Model for the Targeted Allograft

Abstract

Allogeneic hematopoietic cell transplantation is a fundamental part of the treatment of hematologic malignancies and marrow failure syndromes, but complications including graft-versus-host disease, prolonged immune deficiency and infection, and organ toxicities, as well as relapse, remain obstacles to improved overall survival. As the cellular characteristics of the allograft can exert significant impact on outcomes, the development of more strategically designed grafts represents a rich area for therapeutic intervention. We describe the use of ex vivo T cell–depleted grafts as a model for the targeted graft and review evolving knowledge and approaches for further refinement of allografts to improve patient outcomes.

Keyword(s): allogeneic hematopoietic cell transplantation, graft-versus-host disease, immune reconstitution, T cell depletion
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-120617-041210
2019-01-27
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/med/70/1/annurev-med-120617-041210.html?itemId=/content/journals/10.1146/annurev-med-120617-041210&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Jakubowski AA, Small TN, Young JW et al. 2007. T cell–depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood 110:4552–59
     [Google Scholar]
  2. 2.  Jakubowski AA, Small TN, Kernan NA et al. 2011. T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies. Biol. Blood Marrow Transplant. 17:1335–42
     [Google Scholar]
  3. 3.  Devine SM, Carter S, Soiffer RJ et al. 2011. Low risk of chronic graft-versus-host disease and relapse associated with T cell-depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: results of the blood and marrow transplant clinical trials network protocol 0303. Biol. Blood Marrow Transplant. 17:1343–51
     [Google Scholar]
  4. 4.  Keever-Taylor CA, Devine SM, Soiffer RJ et al. 2012. Characteristics of CliniMACS® System CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia—Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. Biol. Blood Marrow Transplant. 18:690–97
     [Google Scholar]
  5. 5.  Kernan NA, Collins NH, Juliano L et al. 1986. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood 68:770–73
     [Google Scholar]
  6. 6.  Papadopoulos EB, Carabasi MH, Castro-Malaspina H et al. 1998. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 91:1083–90
     [Google Scholar]
  7. 7.  Bayraktar UD, de Lima M, Saliba RM et al. 2013. Ex vivo T cell-depleted versus unmodified allografts in patients with acute myeloid leukemia in first complete remission. Biol. Blood Marrow Transplant. 19:898–903
     [Google Scholar]
  8. 8.  Alyea EP, Weller E, Fisher DC et al. 2002. Comparable outcome with T-cell-depleted unrelated-donor versus related-donor allogeneic bone marrow transplantation. Biol. Blood Marrow Transplant. 8:601–7
     [Google Scholar]
  9. 9.  Aversa F, Terenzi A, Carotti A et al. 1999. Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia. J. Clin. Oncol. 17:1545–50
     [Google Scholar]
  10. 10.  Jagasia M, Avora M, Flowers ME et al. 2012. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119:296–307
     [Google Scholar]
  11. 11.  Jagasia MH, Greinix HT, Arora M et al. 2015. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol. Blood Marrow Transplant. 21:389–401
     [Google Scholar]
  12. 12.  Cho C, Hsu M, Barba P et al. 2017. Long-term prognosis for 1-year relapse-free survivors of CD34+ cell-selected allogeneic hematopoietic stem cell transplantation: a landmark analysis. Bone Marrow Transplant 52:1629–36
     [Google Scholar]
  13. 13.  Young JW, Papadopoulos EB, Cunningham I et al. 1992. T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission. Blood 79:3380–87
     [Google Scholar]
  14. 14.  Martin PJ, Hansen JA, Buckner CD et al. 1985. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 66:664–72
     [Google Scholar]
  15. 15.  Martin PJ, Hansen JA, Torok-Storb B et al. 1988. Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. Bone Marrow Transplant 3:437–44
     [Google Scholar]
  16. 16.  Sehn LH, Alyea EP, Weller E et al. 1999. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion. J. Clin. Oncol. 17:561–68
     [Google Scholar]
  17. 17.  Lewin SR, Heller G, Zhang L et al. 2002. Direct evidence for new T-cell generation by patients after either T-cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood 100:2235–42
     [Google Scholar]
  18. 18.  Small TN, Papadopoulos EB, Boulad F et al. 1999. Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 93:467–80
     [Google Scholar]
  19. 19.  Small TN, Avigan D, Dupont B et al. 1997. Immune reconstitution following T-cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis. Biol. Blood Marrow Transplant. 3:65–75
     [Google Scholar]
  20. 20.  Huang YT, Kim SJ, Lee YJ et al. 2017. Co-infections by double-stranded DNA viruses after ex vivo T cell–depleted, CD34+ selected hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 23:1759–66
     [Google Scholar]
  21. 21.  Lee YJ, Huang YT, Kim SJ et al. 2016. Adenovirus viremia in adult CD34+ selected hematopoietic cell transplant recipients: low incidence and high clinical impact. Biol. Blood Marrow Transplant. 22:174–78
     [Google Scholar]
  22. 22.  Goldberg JD, Zheng J, Ratan R et al. 2017. Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leukemia Lymphoma 58:1859–71
     [Google Scholar]
  23. 23.  Huang YT, Neofytos D, Foldi J et al. 2016. Cytomegalovirus infection after CD34+-selected hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 22:1480–86
     [Google Scholar]
  24. 24.  Perales MA, Goldberg JD, Yuan J et al. 2012. Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation. Blood 120:4882–91
     [Google Scholar]
  25. 25.  Goldberg GL, King CG, Nejat RA et al. 2009. Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation. J. Immunol. 182:5846–54
     [Google Scholar]
  26. 26.  Velardi E, Tsai JJ, Holland AM et al. 2014. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling. J. Exp. Med. 211:2341–49
     [Google Scholar]
  27. 27.  Koehne G, Hasan A, Doubrovina E et al. 2015. Immunotherapy with donor T cells sensitized with overlapping pentadecapeptides for treatment of persistent cytomegalovirus infection or viremia. Biol. Blood Marrow Transplant. 21:1663–78
     [Google Scholar]
  28. 28.  Doubrovina E, Oflaz-Sozmen B, Prockop SE et al. 2012. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood 119:2644–56
     [Google Scholar]
  29. 29.  Scott BL, Pasquini MC, Logan BR et al. 2017. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J. Clin. Oncol. 35:1154–61
     [Google Scholar]
  30. 30.  Shah GL, Scordo M, Kosuri S et al. 2018. Impact of toxicity on survival for older adult patients after CD34+ selected allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 24:142–49
     [Google Scholar]
  31. 31.  Sorror ML, Maris MB, Storb R et al. 2005. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106:2912–19
     [Google Scholar]
  32. 32.  Aversa F, Tabilio A, Velardi A 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. 339:1186–93
     [Google Scholar]
  33. 33.  Aversa F, Terenzi A, Tabilio A et al. 2005. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J. Clin. Oncol. 23:3447–54
     [Google Scholar]
  34. 34.  Sestili S, Labopin M, Ruggeri A et al. 2018. T-cell-depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: a study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT). Cancer 124:2142–50
     [Google Scholar]
  35. 35.  Martelli MF, Di Ianni M, Ruggeri L et al. 2014. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood 124:638–44
     [Google Scholar]
  36. 36.  Federmann B, Bornhauser M, Meisner C et al. 2012. Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study. Haematologica 97:1523–31
     [Google Scholar]
  37. 37.  Diamond DJ, Chang KL, Jenkins KA et al. 1995. Immunohistochemical analysis of T cell phenotypes in patients with graft-versus-host disease following allogeneic bone marrow transplantation. Transplantation 59:1436–44
     [Google Scholar]
  38. 38.  Kawanishi Y, Passweg J, Drobyski WR et al. 1997. Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation. Bone Marrow Transplant 19:1069–77
     [Google Scholar]
  39. 39.  Perko R, Kang G, Sunkara A et al. 2015. Gamma delta T cell reconstitution is associated with fewer infections and improved event-free survival after hematopoietic stem cell transplantation for pediatric leukemia. Biol. Blood Marrow Transplant. 21:130–36
     [Google Scholar]
  40. 40.  Locatelli F, Merli P, Pagliara D et al. 2017. Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood 130:677–85
     [Google Scholar]
  41. 41.  Rezvani K, Mielke S, Ahmadzadeh M et al. 2006. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 108:1291–97
     [Google Scholar]
  42. 42.  Wolf D, Wolf AM, Fong D et al. 2007. Regulatory T-cells in the graft and the risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Transplantation 83:1107–13
     [Google Scholar]
  43. 43.  Chaidos A, Patterson S, Szydlo R et al. 2012. Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Blood 119:5030–36
     [Google Scholar]
  44. 44.  Pastore D, Delia M, Mestice A et al. 2012. CD3+/Tregs ratio in donor grafts is linked to acute graft-versus-host disease and immunologic recovery after allogeneic peripheral blood stem cell transplantation. Biol. Blood Marrow Transplant. 18:887–93
     [Google Scholar]
  45. 45.  Rosenzwajg M, Dhedin N, Maury S et al. 2011. Regulatory T cell content in the bone marrow graft does not predict the occurrence of acute GVHD. Biol. Blood Marrow Transplant. 17:265–69
     [Google Scholar]
  46. 46.  Vasu S, Geyer S, Bingman A et al. 2016. Granulocyte colony-stimulating factor-mobilized allografts contain activated immune cell subsets associated with risk of acute and chronic graft-versus-host disease. Biol. Blood Marrow Transplant. 22:658–68
     [Google Scholar]
  47. 47.  Loschi M, Porcher R, Peffault de Latour R et al. 2015. High number of memory T cells is associated with higher risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Biol. Blood Marrow Transplant. 21:569–74
     [Google Scholar]
  48. 48.  Yakoub-Agha I, Saule P, Depil S et al. 2006. A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy. Leukemia 20:1557–65
     [Google Scholar]
  49. 49.  Bleakley M, Heimfeld S, Loeb KR et al. 2015. Outcomes of acute leukemia patients transplanted with naïve T cell–depleted stem cell grafts. J. Clin. Investig. 125:2677–89
     [Google Scholar]
  50. 50.  Reshef R, Huffman AP, Gao A et al. 2015. High graft CD8 cell dose predicts improved survival and enables better donor selection in allogeneic stem-cell transplantation with reduced-intensity conditioning. J. Clin. Oncol. 33:2392–98
     [Google Scholar]
  51. 51.  Castro-Malaspina H, Jabubowski AA, Papadopoulos EB et al. 2008. Transplantation in remission improves the disease-free survival of patients with advanced myelodysplastic syndromes treated with myeloablative T cell-depleted stem cell transplants from HLA-identical siblings. Biol. Blood Marrow Transplant. 14:458–68
     [Google Scholar]
  52. 52.  Perales MA, Jenq R, Goldberg JD et al. 2010. Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT. Bone Marrow Transplant 45:1408–16
     [Google Scholar]
  53. 53.  Jakubowski AA, Small TN, Kernan NA et al. 2011. T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies. Biol. Blood Marrow Transplant. 17:1335–42
     [Google Scholar]
  54. 54.  Goldberg JD, Linker A, Kuk D et al. 2013. T cell-depleted stem cell transplantation for adults with high-risk acute lymphoblastic leukemia: long-term survival for patients in first complete remission with a decreased risk of graft-versus-host disease. Biol. Blood Marrow Transplant. 19:208–13
     [Google Scholar]
  55. 55.  Tamari R, Chung SS, Papadopoulos EB et al. 2015. CD34-selected hematopoietic stem cell transplants conditioned with myeloablative regimens and antithymocyte globulin for advanced myelodysplastic syndrome: limited graft-versus-host disease without increased relapse. Biol. Blood Marrow Transplant. 21:2106–14
     [Google Scholar]
  56. 56.  Pasquini MC, Devine S, Mendizabal A et al. 2012. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J. Clin. Oncol. 30:3194–201
     [Google Scholar]
  57. 57.  Hobbs GS, Hamdi A, Hilden PD et al. 2015. Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts. Bone Marrow Transplant 50:493–98
     [Google Scholar]
  58. 58.  Tamari R, Oran B, Hilden P et al. 2018. Allogeneic stem cell transplantation for advanced myelodysplastic syndrome: comparison of outcomes between CD34+ selected and unmodified hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 24:1079–87
     [Google Scholar]
  59. 59.  Barba P, Martino R, Zhou Q et al. 2018. CD34+ cell selection versus reduced-intensity conditioning and unmodified grafts for allogeneic hematopoietic cell transplantation in patients age >50 years with acute myelogenous leukemia and myelodysplastic syndrome. Biol. Blood Marrow Transplant. 24:964–72
     [Google Scholar]
/content/journals/10.1146/annurev-med-120617-041210
Loading
Expanding Therapeutic Opportunities for Hematopoietic Stem Cell Transplantation: T Cell Depletion as a Model for the Targeted Allograft
Annual Review of Medicine 70, 381 (2019); https://doi.org/10.1146/annurev-med-120617-041210
/content/journals/10.1146/annurev-med-120617-041210
/content/journals/10.1146/annurev-med-120617-041210
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error