Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pediatric Transplants

Unrelated donor or partially matched related donor peripheral stem cell transplant with CD34+ selection and CD3+ addback for pediatric patients with leukemias

Bone Marrow Transplantation volume 37, pages 143–149 (2006)Cite this article

Abstract

Unmodified peripheral stem cell transplants are associated with an increased risk of extensive chronic GVHD. T depletion may reduce this risk, but the risk of graft failure or relapse may increase. To decrease the risks of both extensive chronic GVHD and graft failure, we added back a defined dose of CD3+ cells to CD34+ selected PSCs. Twenty-four patients were evaluable for outcome analysis. Donors were unrelated (23) or related (1). Conditioning was thiotepa, cyclophosphamide, and total body irradiation. Cyclosporine was used post transplant. Following CD34+ selection, a total of 5 × 105/kg CD3+ cells were infused. Donors were matched for 12 patients. The median CD34+ dose infused was 7.1 × 106/kg. Engraftment occurred in all patients at a median of 14 days (10–19). Twelve patients are alive in remission 15–34 months (median, 25) post PSCT. GVHD occurred in 17 patients, but was >grade II in only 2. Chronic GVHD occurred in 61.5% of evaluable patients, but was limited to skin and perioral cavity. Two patients relapsed, and 10 patients died of non-relapse causes. This study demonstrates that PSCT with CD34+ selection and a defined dose of CD3+ results in prompt engraftment and may limit development of extensive chronic GVHD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Eapen M, Horowitz MM, Klein JP, Champlin RE, Loberiza Jr FR, Ringden O et al. Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: The Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry. J Clin Oncol 2004; 22: 4872–4880.

    Article  PubMed  Google Scholar 

  2. Blaise D, Kuentz M, Fortanier C, Bourhis JH, Milpied N, Sutton L et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: A report from the societe francaise de greffe de moelle. J Clin Oncol 2000; 18: 537–546.

    Article  CAS  PubMed  Google Scholar 

  3. Storek J, Dawson MA, Storer B, Stevens-Ayers T, Maloney DG, Marr KA et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001; 97: 3380–3389.

    Article  CAS  PubMed  Google Scholar 

  4. Ringden O, Labopin M, Bacigalupo A, Arcese W, Schaefer UW, Willemze R et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol 2002; 20: 4655–4664.

    Article  CAS  PubMed  Google Scholar 

  5. Ottinger H, Beelen D, Schuelen B, Schaefer UW, Grosse-Wilde H . Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood 1996; 88: 2775–2779.

    CAS  PubMed  Google Scholar 

  6. Glass B, Uharek L, Zeis M, Dreger P, Loffler H, Steinmann J et al. Allogeneic peripheral blood progenitor cell transplantation in a murine model: evidence for an improved graft-versus-leukemia effect. Blood 1997; 90: 1694–1700.

    CAS  PubMed  Google Scholar 

  7. Paveletic Z, Joshi S, Pirruccello S, Tarantolo SR, Kollath J, Reed EC et al. Lymphocyte reconstitution after allogeneic blood stem transplantation for hematologic malignancies. Bone Marrow Transplant 1998; 21: 33–41.

    Article  Google Scholar 

  8. Mohty M, Kuentz M, Michallet M, Bourhis JH, Milpied N, Sutton L et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100: 3128–3134.

    Article  CAS  PubMed  Google Scholar 

  9. Zeng D, Dejbakhsh-Jones S, Strober S . Granulocyte colony-stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: Impact on blood progenitor cell transplantation. Blood 1997; 90: 453–463.

    CAS  PubMed  Google Scholar 

  10. Korbling M, Huh YO, Durett A, Mirza N, Miller P, Engel H et al. Allogeneic peripheral blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease. Blood 1995; 86: 2842–2848.

    CAS  PubMed  Google Scholar 

  11. Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Besinger WI et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100: 415–419.

    Article  CAS  PubMed  Google Scholar 

  12. Levine J, Kletzel M, Yanik G, Hutchinson RJ, Koehler M, Neudorf S . Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a higher incidence of chronic GVHD. Bone Marrow Transplant 2000; 25: 13–18.

    Article  CAS  PubMed  Google Scholar 

  13. Brown RA, Adkins D, Khoury H, Vij R, Goodnough LT, DiPersio JF . Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients: graft-versus-host disease and transplant-related mortality. J Clin Oncol 1999; 17: 806–812.

    Article  CAS  PubMed  Google Scholar 

  14. Champlin R, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Corneilissen JJ et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. Blood 2000; 95: 3702–3709.

    CAS  PubMed  Google Scholar 

  15. Bornhauser M, Platzbecker U, Theuser C, Holig K, Ehninger G . CD34+-enriched peripheral blood progenitor cells from unrelated donors for allografting of adult patients: high risk of graft failure, infection and relapse despite donor lymphocyte add-back. Br J Haematol 2002; 118: 1095–1103.

    Article  PubMed  Google Scholar 

  16. Nakamura R, Bahceci E, Read EJ, Leitman SF, Carter CS, Childs R et al. Transplant dose of CD34+ and CD3+ cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back. Br J Haematol 2001; 115: 95–104.

    Article  CAS  PubMed  Google Scholar 

  17. Ng J, Katovich-Hurley CK, Baxter-Lowe LA, Chopek M, Coppo PA, Hegland J et al. Large-scale oligonucleotide typing for HLA-DRB1/3/4 and HLA-DQB1 is highly accurate, specific, and reliable. Tissue Antigens 1993; 42: 473–479.

    Article  CAS  PubMed  Google Scholar 

  18. Noreen HJ, Yu N, Setterholm M, Ohashi M, Baisch J, Endres R et al. Validation of DNA-based HLA-A and HLA-B testing of volunteers for a Bone Marrow Registry through parallel testing with serology. Tissue Antigens 2001; 57: 221–229.

    Article  CAS  PubMed  Google Scholar 

  19. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  20. Elmaagacli A, Basoglu S, Peceny R, Trenschel R, Ottinger H, Lollert A et al. Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia. Blood 2002; 99: 1130–1135.

    CAS  PubMed  Google Scholar 

  21. Ringden O, Remberger M, Runde V, Bornhauser M, Blau IW, Basara N et al. Peripheral blood stem cell transplantation from unrelated donors: A comparison with marrow transplantation. Blood 1999; 94: 455–464.

    CAS  PubMed  Google Scholar 

  22. Remberger M, Ringden O, Blau IW, Ottinger H, Kremens B, Kiehl MG . No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors. Blood 2001; 98: 1739–1745.

    Article  CAS  PubMed  Google Scholar 

  23. Remberger M, Beelen DW, Fauser A, Basara N, Basu O, Ringden O . Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood 2005; 105: 548–551.

    Article  CAS  PubMed  Google Scholar 

  24. Garderet L, Labopin M, Gorin NC, Polge E, Fouillard L, Ehninger GE et al. Patients with acute lymphoblastic leukemia allografted with a matched unrelated donor may have a lower survival with a peripheral blood stem cell graft compared to bone marrow. Bone Marrow Transplant 2003; 31: 23–29.

    Article  CAS  PubMed  Google Scholar 

  25. Champlin R, Passweg J, Zhang M, Rowlings PA, Pelz CJ, Atkinson KA 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. Blood 2000; 95: 3996–4000.

    CAS  PubMed  Google Scholar 

  26. Bunin N, Aplenc R, Leahey A, Magira E, Grupp S, Pierson G et al. Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias. Bone Marrow Transplant 2005; 35: 151–158.

    Article  CAS  PubMed  Google Scholar 

  27. Bahceci E, Read E, Leitman S, Childs R, Dunbar C, Young NS et al. CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical hematopoietic stem cell transplantation for haematological malignancies. Br J Haematol 2000; 108: 408–414.

    Article  CAS  PubMed  Google Scholar 

  28. Zaucha J, Gooley T, Bensinger W, Heimfeld S, Chauncey TR, Zaucha R et al. CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation. Blood 2001; 98: 3221–3227.

    Article  CAS  PubMed  Google Scholar 

  29. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C 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. Blood 1994; 84: 3948–3955.

    CAS  PubMed  Google Scholar 

  30. Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A et al. Megadose transplantation of purified peripheral blood CD34+ progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001; 27: 777–783.

    Article  CAS  PubMed  Google Scholar 

  31. Lang P, Handgretinger R, Niethammer D, Schlegel PG, Schumm M, Greil J et al. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood 2003; 101: 1630–1636.

    Article  CAS  PubMed  Google Scholar 

  32. Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S et al. The number of donor CD3+ cells is the most important factor for graft failure after allogeneic transplantation of CD34+ selected cells from peripheral blood from HLA-identical siblings. Blood 2001; 97: 383–387.

    Article  CAS  PubMed  Google Scholar 

  33. Urbano-Ispizua A, Rozman C, Martinez C, Marin P, Briones J, Rovira M et al. Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood. Blood 1997; 89: 3967–3973.

    CAS  PubMed  Google Scholar 

  34. Urbano-Ispizua A, Carreras E, Marin P, Rovira M, Martinez C, Fernandez-Aviles F et al. Allogeneic transplantation of CD34(+) selected cells from peripheral blood from human leukocyte antigen-identical siblings: detrimental effect of a high number of donor CD34(+) cells? Blood 2001; 98: 2352–2357.

    Article  CAS  PubMed  Google Scholar 

  35. Mohty M, Bilger K, Jourdan E, Kuentz M, Michallet M, Bourhis JH et al. Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation. Leukemia 2003; 17: 869–875.

    Article  CAS  PubMed  Google Scholar 

  36. Przepiorka D, Smith TL, Folloder J, Khouri I, Ueno NT, Mehra R et al. Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 1999; 94: 1465–1470.

    CAS  PubMed  Google Scholar 

  37. Madero L, Vicent M, Sevilla J, Prudencio M, Rodriguez F, Diaz MA . Engraftment syndrome in children undergoing autologous peripheral blood progenitor cell transplantation. Bone Marrow Transplant 2002; 30: 355–358.

    Article  CAS  PubMed  Google Scholar 

  38. Lee C-K, Gingrich R, Hohl R, Ajram K . Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. Bone Marrow Transplant 1995; 16: 175–182.

    CAS  PubMed  Google Scholar 

  39. Edenfield W, Moores L, Goodwin G, Lee N . An engraftment syndrome in autologous stem cell transplantation related to mononuclear cell dose. Bone Marrow Transplant 2000; 25: 405–409.

    Article  CAS  PubMed  Google Scholar 

  40. Ravoet C, Feremans W, Husson B, Majois F, Kentos A, Lambermont M et al. Clinical evidence for engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation. Bone Marrow Transplant 1996; 18: 943–947.

    CAS  PubMed  Google Scholar 

  41. Cahill R, Spitzer T, Mazumder A . Marrow engraftment and clinical manifestations of capillary leak syndrome. Bone Marrow Transplant 1996; 18: 177–184.

    CAS  PubMed  Google Scholar 

  42. Ho V, Kim H, Hochberg E, Hochberg EP, Cutler C, Lee SJ et al. Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease. Bone Marrow Transplant 2004; 34: 987–994.

    Article  CAS  PubMed  Google Scholar 

  43. Bacigalupo A, Mordini N, Pitto A, Piaggio G, Podesta M, Benvenuto F et al. Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies: severe immunodeficiency and related complications. Brit J Haematol 1997; 98: 760–766.

    Article  CAS  Google Scholar 

  44. Zaia J, Gallez-Hawkins G, Tegtmeier B, ter Veer A, Li Z, Niland JC et al. Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma. J Infect Dis 1997; 176: 782–785.

    Article  CAS  PubMed  Google Scholar 

  45. Einsele H, Hebart H, Kauffmann-Schneider C, Sinzger C, Jahn G, Bader P et al. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 2000; 25: 757–763.

    Article  CAS  PubMed  Google Scholar 

  46. Eckle T, Prix L, Jahn G, Klingebiel T, Handgretinger R, Selle B et al. Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood 2000; 96: 3286–3289.

    CAS  PubMed  Google Scholar 

  47. Eckle T, Lang P, Rix L, Jahn G, Klingebiel T, Handgretinger R et al. Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant 2002; 30: 433–439.

    Article  CAS  PubMed  Google Scholar 

  48. Appleton A, Sviland L, Peiris J, Taylor CE, Wilkes J, Green MA et al. Human herpes virus-6 infection in marrow graft recipients: role in pathogenesis of graft-versus-host disease, from the Newcastle upon Tyne Bone Marrow Transplant Group. Bone Marrow Transplant 1995; 16: 777–782.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    N Bunin, R Aplenc, S Grupp, G Pierson & D Monos

Authors
  1. N Bunin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Aplenc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Grupp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Pierson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Monos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Bunin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bunin, N., Aplenc, R., Grupp, S. et al. Unrelated donor or partially matched related donor peripheral stem cell transplant with CD34+ selection and CD3+ addback for pediatric patients with leukemias. Bone Marrow Transplant 37, 143–149 (2006). https://doi.org/10.1038/sj.bmt.1705211

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705211

Keywords

This article is cited by

Search

Advanced search

Quick links