The evolution of T‐cell depletion in haploidentical stem‐cell transplantation

T‐cell depletion (TCD) can prevent the onset of graft‐versus‐host disease (GvHD) in animal models of bone marrow transplantation; this manipulation enabled the successful application in the 1980s of T‐cell depleted bone marrow (BM) for the treatment of babies with severe combined immune deficiency (SCID). However, in leukaemia patients, implementation of T‐cell depletion has been more difficult, especially due to high rate of graft‐rejection, leukaemia relapse and delayed immune reconstitution. These hurdles were gradually overcome by modifying the cell composition of the graft, and by reducing the toxicities associated with conditioning protocols. Although no ‘gold standard’ TCD method exists, T‐cell depletion in its modern forms could offer clinical benefit, even for patients with a matched sibling donor.

[1]  T. Fleisher.  Transplantation Outcomes for Severe Combined Immunodeficiency 2000–2009 , 2015, Pediatrics.

[2]  K. Loeb,et al.  Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. , 2015, The Journal of clinical investigation.

[3]  R. Krance,et al.  Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. , 2015, Blood.

[4]  Shannon R. McCurdy,et al.  Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. , 2015, Blood.

[5]  A. Moretta,et al.  γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes. , 2015, Blood.

[6]  C. Pui,et al.  Rapid Memory T-cell Reconstitution Recapitulating CD45RA-depleted Haploidentical Transplant Graft Content in Patients with Hematologic Malignancies , 2015, Bone Marrow Transplantation.

[7]  J. Dipersio,et al.  Infusion of Donor Lymphocytes Genetically Engineered to Express the Herpes Simplex Virus Thymidine Kinase (HSV-TK) Suicide Gene after Haploidentical Hematopoietic Stem Cell Transplantation (HSCT): Preliminary Efficacy Data from the Randomized TK008 Study , 2014 .

[8]  Christopher G. Kanakry,et al.  Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  B. Liu,et al.  Stem Cell Therapy in Autoimmune Rheumatic Diseases: a Comprehensive Review , 2014, Clinical Reviews in Allergy & Immunology.

[10]  Y. Reisner,et al.  Megadose stem cell administration as a route to mixed chimerism. , 2014, Current opinion in organ transplantation.

[11]  C. Cancrini,et al.  HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. , 2014, Blood.

[12]  L. Notarangelo,et al.  Transplantation outcomes for severe combined immunodeficiency, 2000-2009. , 2014, The New England journal of medicine.

[13]  B. Falini,et al.  HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. , 2014, Blood.

[14]  X-j Huang,et al.  Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers , 2014, Bone Marrow Transplantation.

[15]  S. Reich-Zeliger,et al.  Murine anti-third-party central-memory CD8(+) T cells promote hematopoietic chimerism under mild conditioning: lymph-node sequestration and deletion of anti-donor T cells. , 2013, Blood.

[16]  Richard J. Jones,et al.  HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. , 2012, Blood.

[17]  A. Tosti,et al.  Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT , 2012, Bone Marrow Transplantation.

[18]  C. Meisner,et al.  Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study , 2012, Haematologica.

[19]  M. Abecassis,et al.  Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation , 2012, Science Translational Medicine.

[20]  A. Barrett,et al.  Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies. , 2011, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[21]  Adrian P Gee,et al.  Inducible apoptosis as a safety switch for adoptive cell therapy. , 2011, The New England journal of medicine.

[22]  P. Hari,et al.  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. , 2011, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[23]  G. Papanicolaou,et al.  T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies. , 2011, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[24]  M. Sykes,et al.  Translational studies in hematopoietic cell transplantation: treatment of hematologic malignancies as a stepping stone to tolerance induction. , 2011, Seminars in immunology.

[25]  B. Falini,et al.  Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. , 2011, Blood.

[26]  R. Buckley.  Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes , 2011, Immunologic research.

[27]  M. Shlomchik,et al.  A repertoire-independent and cell-intrinsic defect in murine GVHD induction by effector memory T cells. , 2011, Blood.

[28]  D. Hagin,et al.  Haploidentical bone marrow transplantation in primary immune deficiency: stem cell selection and manipulation. , 2011, Hematology/oncology clinics of North America.

[29]  P. Tazzari,et al.  Quantitatively different red cell/nucleated cell chimerism in patients with long-term, persistent hematopoietic mixed chimerism after bone marrow transplantation for thalassemia major or sickle cell disease , 2010, Haematologica.

[30]  E. Ophir,et al.  Induction of tolerance to bone marrow allografts by donor-derived host nonreactive ex vivo-induced central memory CD8 T cells. , 2010, Blood.

[31]  P. Veys,et al.  Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy. , 2010, Blood.

[32]  H. Einsele,et al.  Selective depletion of alloreactive T cells by targeted therapy of heat shock protein 90: a novel strategy for control of graft-versus-host disease. , 2009, Blood.

[33]  T. Hügle,et al.  Allogeneic hematopoietic SCT for patients with autoimmune diseases , 2009, Bone Marrow Transplantation.

[34]  C. Civin,et al.  Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand1 , 2009, The Journal of Immunology.

[35]  D. Jain,et al.  Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia1 , 2009, The Journal of Immunology.

[36]  A. Ganser,et al.  Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. , 2009, The Lancet. Oncology.

[37]  Allen R. Chen,et al.  HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. , 2008, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[38]  K. Rezvani,et al.  A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique. , 2008, Blood.

[39]  E. Engleman,et al.  Tolerance and chimerism after renal and hematopoietic-cell transplantation. , 2008, The New England journal of medicine.

[40]  V. Sharma,et al.  HLA-mismatched renal transplantation without maintenance immunosuppression. , 2008, The New England journal of medicine.

[41]  J. Mehta,et al.  Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation , 2007, Bone Marrow Transplantation.

[42]  A. Bacigalupo.  Management of acute graft‐versus‐host disease , 2007, British journal of haematology.

[43]  R. Krance,et al.  Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. , 2006, Blood.

[44]  J. Falkenburg,et al.  Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath ‘in the bag’ as T-cell depletion: the Leiden experience , 2006, Bone Marrow Transplantation.

[45]  T. Klingebiel,et al.  A Comparison between Three Graft Manipulation Methods for Haploidentical Stem Cell Transplantation in Pediatric Patients: Preliminary Results of a Pilot Study , 2005, Klinische Pädiatrie.

[46]  C. Mecucci,et al.  Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Catherine J. Wu,et al.  Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. , 2003, Blood.

[48]  C. Fathman,et al.  CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation , 2003, Nature Medicine.

[49]  M. Shlomchik,et al.  Memory CD4+ T cells do not induce graft-versus-host disease. , 2003, The Journal of clinical investigation.

[50]  T. Klingebiel,et al.  Megadose transplantation of highly purified haploidentical stem cells: current results and future prospects , 2003, Pediatric transplantation.

[51]  J. Garcia-conde,et al.  Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. , 2002, Blood.

[52]  A. Fischer,et al.  Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study , 2002, The Lancet.

[53]  A. Berrebi,et al.  Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34(+) cells. , 2002, Blood.

[54]  P. Mcsweeney,et al.  High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review. , 2002, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[55]  T. Klingebiel,et al.  Megadose transplantation of purified peripheral blood CD34+progenitor cells from HLA-mismatched parental donors in children , 2001, Bone Marrow Transplantation.

[56]  R. Good.  Progress toward Production of Immunologic Tolerance with No or Minimal Toxic Immunosuppression for Prevention of Immunodeficiency and Autoimmune Diseases , 2000, World Journal of Surgery.

[57]  J. Klein,et al.  T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. , 2000, Blood.

[58]  J. Gribben,et al.  Transplantation of anergic histoincompatible bone marrow allografts. , 1999, The New England journal of medicine.

[59]  A. Berrebi,et al.  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. , 1998, Transplantation.

[60]  C. Dunbar,et al.  CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies , 1996 .

[61]  E. Romond,et al.  Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant. , 1996, Transplantation.

[62]  Y. Reisner,et al.  Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice , 1995, Nature Medicine.

[63]  M. Martelli,et al.  Bone marrow transplantation across HLA barriers by increasing the number of transplanted cells. , 1995, Immunology today.

[64]  F. Aversa,et al.  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. , 1994, Blood.

[65]  T. Holyoake,et al.  CD34+ positive haemopoietic cells: biology and clinical applications. , 1994, Blood reviews.

[66]  F. Appelbaum,et al.  Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor , 1993 .

[67]  S. Heimfeld,et al.  Peripheral blood stem cell mobilization after stem cell factor or G-CSF treatment: rapid enrichment for stem and progenitor cells using the CEPRATE immunoaffinity separation system. , 1992, Transplantation proceedings.

[68]  B. Glass,et al.  Influence of cell dose and graft-versus-host reactivity on rejection rates after allogeneic bone marrow transplantation. , 1992, Blood.

[69]  T. Lapidot,et al.  Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts. , 1989, Blood.

[70]  G. Hale,et al.  T CELL DEPLETION WITH CAMPATH‐1 IN ALLOGENEIC BONE MARROW TRANSPLANTATION , 1988, Transplantation.

[71]  B. Dupont,et al.  Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. , 1987, Transplantation.

[72]  B. Dupont,et al.  Evaluation of HLA‐Haplotype Disparate Parental Marrow Grafts Depleted of T Lymphocytes by Differential Agglutination with a Soybean Lectin and E‐Rosette Depletion for the Treatment of Severe Combined Immunodeficiency 1 , 1986, Vox sanguinis.

[73]  D. Douer,et al.  Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[74]  B. Dupont,et al.  QUANTITATION OF T LYMPHOCYTES IN HUMAN BONE MARROW BY A LIMITING DILUTION ASSAY , 1985, Transplantation.

[75]  R. Miller,et al.  Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. I. CTL clones express strong anti-self suppressive activity , 1984, The Journal of experimental medicine.

[76]  G. Hale,et al.  ELIMINATION OF GRAFT-VERSUS-HOST DISEASE BY IN-VITRO DEPLETION OF ALLOREACTIVE LYMPHOCYTES WITH A MONOCLONAL RAT ANTI-HUMAN LYMPHOCYTE ANTIBODY (CAMPATH-1) , 1984, The Lancet.

[77]  B. Dupont,et al.  Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. , 1983, Blood.

[78]  E. Reinherz,et al.  Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[79]  J. Kersey,et al.  PRETREATMENT OF DONOR BONE MARROW WITH MONOCLONAL ANTIBODY OKT3 FOR PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE IN ALLOGENEIC HISTOCOMPATIBLE BONE-MARROW TRANSPLANTATION , 1982, The Lancet.

[80]  S. Murphy,et al.  Failure of a pan-reactive anti-T cell antibody, OKT 3, to prevent graft versus host disease in severe combined immunodeficiency. , 1982, The Journal of pediatrics.

[81]  G. Janossy,et al.  USE OF ANTI-T-CELL MONOCLONAL ANTIBODY OKT3 TO PREVENT ACUTE GRAFT-VERSUS-HOST DISEASE IN ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR ACUTE LEUKAEMIA , 1982, The Lancet.

[82]  R. Good,et al.  TRANSPLANTATION FOR ACUTE LEUKAEMIA WITH HLA-A AND B NONIDENTICAL PARENTAL MARROW CELLS FRACTIONATED WITH SOYBEAN AGGLUTININ AND SHEEP RED BLOOD CELLS , 1981, The Lancet.

[83]  K. Wilms,et al.  Effect of anti-T-cell globulin on GVHD in leukemic patients treated with BMT. , 1981, Transplantation proceedings.

[84]  Richard G. Miller.  An immunological suppressor cell inactivating cytotoxic T-lymphocyte precursor cells recognizing it , 1980, Nature.

[85]  A. Meshorer,et al.  Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[86]  J. Sprent,et al.  Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras , 1975, The Journal of experimental medicine.

[87]  E. Saltzstein,et al.  Graft versus host inhibition: fetal liver and thymus cells to minimize secondary disease. , 1969, Science.

[88]  Williams Ja.  SKIN LESIONS AS RESERVOIRS OF HOSPITAL INFECTION. , 1965 .

[89]  W. Quinton,et al.  PROLONGED PERITONEAL DIALYSIS FOR CHRONIC RENAL FAILURE. , 1964, Lancet.

[90]  C. Pui,et al.  Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies , 2015, Bone Marrow Transplantation.

[91]  P. Thomas,et al.  Gamma delta T cell reconstitution is associated with fewer infections and improved event-free survival after hematopoietic stem cell transplantation for pediatric leukemia. , 2015, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[92]  A. Marciniak-Czochra,et al.  The impact of CD34+ cell dose on engraftment after SCTs: personalized estimates based on mathematical modeling , 2014, Bone Marrow Transplantation.

[93]  T. Lamparelli,et al.  Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. , 2013, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[94]  J. Stockman.  Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease , 2011 .

[95]  L. Kanz,et al.  Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. , 2008, Blood cells, molecules & diseases.

[96]  J. Mehta,et al.  Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. , 2007, Bone marrow transplantation.

[97]  M. Girardi.  Immunosurveillance and immunoregulation by gammadelta T cells. , 2006, The Journal of investigative dermatology.

[98]  M. Girardi.  Immunosurveillance and Immunoregulation by γδ T Cells , 2006 .

[99]  C. Dunbar,et al.  CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. , 1996, Blood.

[100]  J. Singer,et al.  Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor. , 1993, Blood.

[101]  M. Fackler,et al.  Positive stem cell selection--basic science. , 1990, Progress in clinical and biological research.

[102]  R. Handgretinger,et al.  The efficiency of a new cell separation technique in bone marrow purging without damaging the purged tumor cells. , 1990, Progress in clinical and biological research.

[103]  R. Storb,et al.  Donors other than HLA-identical siblings. , 1989, Progress in clinical and biological research.

[104]  D. van der Waaij,et al.  The use of stem-cell grafts in combined immune deficiencies. , 1975, Birth defects original article series.