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Allografting

Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution

Summary:

We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6–49), and the median time between diagnosis and transplant 1 month (range, 1–24). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days −7 to −4 and antithymocyte globulin (30 mg/kg per day) on days −4 to −2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 × 106 and 0.3 × 106/kg, respectively. The median time taken to achieve a neutrophil count >0.5 × 109/l was 12 days and to recover a platelet count >20 × 109/l, 13 days. Two patients developed acute GVHD grade I–II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4–73), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.

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References

  1. Russell NH, Gratwohl A, Schmitz N . Developments in allogeneic peripheral blood progenitor cell transplantation. Br J Haematol 1998; 103: 594–600.

    Article  CAS  PubMed  Google Scholar 

  2. Bensinger WI, Martin PJ, Storer B et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Eng J Med 2001; 344: 175–181.

    Article  CAS  Google Scholar 

  3. Schmitz N, Beksac M, Hasenclever D et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood 2002; 100: 761–767.

    Article  CAS  PubMed  Google Scholar 

  4. Blaise D, Kuentz M, Fortainer C et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societé Française de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.

    Article  CAS  PubMed  Google Scholar 

  5. Bensinger WI, Clift R, Martin P et al. Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation. Blood 1996; 88: 2794–2800.

    CAS  PubMed  Google Scholar 

  6. Pavletic Z, Bishop M, Tarantolo S et al. Hematopoietic recovery after allogeneic blood-stem cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies. J Clin Oncol 1997; 15: 1608–1616.

    Article  CAS  PubMed  Google Scholar 

  7. Urbano-Ispizua A, García-Conde J, Brunet S et al. High incidence of chronic graft versus host disease after allogeneic peripheral blood progenitor cell transplantation. Haematologica 1997; 82: 683–689.

    CAS  PubMed  Google Scholar 

  8. Brown RA, Adkins D, Khoury H et al. 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 

  9. Storek J, Gooley T, Siadak M et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease. Blood 1997; 90: 4705–4709.

    CAS  PubMed  Google Scholar 

  10. Ho VT, Soiffer RJ . The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic stem cell transplantation. Blood 2001; 98: 3192–3204.

    Article  CAS  PubMed  Google Scholar 

  11. Link H, Arseniev L, Bähre O et al. Transplantation of allogeneic CD34+ blood cells. Blood 1996; 87: 4903–4909.

    CAS  PubMed  Google Scholar 

  12. Finke J, Brugger W, Bertz H et al. Allogeneic transplantation of positively selected peripheral blood CD34+ progenitor cells from matched related donors. Bone Marrow Transplant 1996; 18: 1081–1086.

    CAS  PubMed  Google Scholar 

  13. Urbano-Ispizua A, Rozman C, Martínez C 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 

  14. Benesch M, Urban C, Sykora KW et al. Transplantation of highly purified CD34+ progenitor cells from alternative donors in children with refractory severe aplastic anaemia. Br J Haematol 2004; 125: 58–63.

    Article  PubMed  Google Scholar 

  15. Urbano-Ispizua A, Solano C, Brunet S et al. Allogeneic transplantation of selected CD34+ cells from peripheral blood: experience of 62 cases using immuno-adsorption or immunomagnetic technique. Spanish Group of Allo-PBT. Bone Marrow Transplant 1998; 22: 519–525.

    Article  CAS  PubMed  Google Scholar 

  16. Antin JH, Childs R, Filipovich AH et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietc transplantation: recommendations from a workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001; 7: 473–485.

    Article  CAS  PubMed  Google Scholar 

  17. Thomas ED . Marrow transplantation for nonmalignant disorders. New Eng J Med 1985; 312: 46–48.

    Article  CAS  PubMed  Google Scholar 

  18. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.

    Article  CAS  PubMed  Google Scholar 

  19. Locatelli F, Bruno B, Zecca M et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from HLA-identical sibling : results of a GITMO/EBMT randomized trial. Blood 2000; 96: 1690–1697.

    CAS  PubMed  Google Scholar 

  20. Passweg JR, Socié G, Hinterberger W et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved. Blood 1997; 90: 858–864.

    CAS  PubMed  Google Scholar 

  21. Gluckman E, Horowitz M, Champlin RE et al. Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome. Blood 1992; 79: 269–275.

    CAS  PubMed  Google Scholar 

  22. Storb R, Leisenring W, Anasetti C et al. Long-term follow-up of allogeneic marrow transplants in patients with aplastic anemia conditioned by cyclophosphamide combined with antithymocyte globulin. Blood 1994; 83: 2749–2750.

    CAS  PubMed  Google Scholar 

  23. Petterson J, Prentice HG, Brenner MK et al. Graft failure following HLA matched T-lymphocyte depleted bone marrow transplantation. Br J Haematol 1986; 63: 221–230.

    Article  Google Scholar 

  24. Doney K, Leisenring W, Storb R et al. Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team. Ann Intern Med 1997; 126: 107–115.

    Article  CAS  PubMed  Google Scholar 

  25. McCann SR, Bacigalupo A, Gluckman E et al. Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. Bone Marrow Transplant 1994; 13: 233–237.

    CAS  PubMed  Google Scholar 

  26. Verdonck LF, Dekker AW, de Gast GC et al. Allogeneic bone marrow transplantation with fixed low number of T cells in the marrow graft. Blood 1994; 83: 3090–3096.

    CAS  PubMed  Google Scholar 

  27. Urbano-Ispizua A, Rozman C, Pimentel P 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 

  28. Naparstek E, Delukina D, Or R et al. Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies. Exp Hematol 1999; 27: 1210–1218.

    Article  CAS  PubMed  Google Scholar 

  29. Urbano-Ispizua A, Rozman C, Pimentel P et al. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood 2002; 100: 724–727.

    Article  CAS  PubMed  Google Scholar 

  30. Gluckman E, Socié G, Devergie A et al. Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up. Blood 1991; 78: 2451–2455.

    CAS  PubMed  Google Scholar 

  31. Deeg HJ, Socie G, Schoch G et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87: 386–392.

    CAS  PubMed  Google Scholar 

  32. Ades L, Mary JV, Robin M et al. Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood 2004; 103: 2490–2497.

    Article  CAS  PubMed  Google Scholar 

  33. Filipovich AH, Vallera DA, Youle RJ et al. Graft versus host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. Transplantation 1987; 44: 62–69.

    Article  CAS  PubMed  Google Scholar 

  34. Atkinson K, Horowitz MM, Gale RP et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990; 75: 2459–2464.

    CAS  PubMed  Google Scholar 

  35. Martínez C, Urbano-Ispizua A, Rozman C et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol 1999; 27: 561–568.

    Article  PubMed  Google Scholar 

  36. Martino R, Rovira M, Carreras E et al. Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD34+-selected transplantation. Haematologica 2001; 86: 1075–7086.

    CAS  PubMed  Google Scholar 

  37. Couriel D, Canosa J, Engler H et al. Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies. Bone Marrow Transplant 1996; 18: 347–353.

    CAS  PubMed  Google Scholar 

  38. Reusser P, Riddell SR, Meyers JD et al. Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 1991; 78: 1373–1380.

    CAS  PubMed  Google Scholar 

  39. Ochs L, Shu XO, Miller J et al. Late infections after allogeneic bone marrow transplantation: comparison of incidence in related and unrelated donor transplant recipients. Blood 1995; 86: 3979–3986.

    CAS  PubMed  Google Scholar 

  40. Manteiga R, Martino R, Sureda A et al. Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem cell transplantation: a single center experience. Bone Marrow Transplant 1998; 22: 899–904.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to M A Sanz.

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de la Rubia, J., Cantero, S., Sanz, G. et al. Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution. Bone Marrow Transplant 36, 325–329 (2005). https://doi.org/10.1038/sj.bmt.1705067

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