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Peripheral Blood Stem Cells

Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study

Bone Marrow Transplantation volume 32, pages 257–264 (2003)Cite this article

Summary:

A total of 61 consecutive adult patients with haematological malignancies with an HLA-identical or one antigen-mismatched haploidentical family donor were randomised to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM). The median observation time was 5 years. Apart from engraftment parameters and acute graft-versus-host disease (GVHD), transplant-related mortality (TRM), incidence and severity of chronic GVHD, relapse, leukaemia-free survival (LFS) and overall survival (OS) were recorded. In the BSC and BM group, respectively, TRM was 8/30 and 4/30 (P=0.405), the incidence of chronic GVHD was 15/26 and 11/30 (P=0.138), extensive chronic GVHD was 10/26 and 4/30 (P=0.034), and relapse one and 10 patients (P=0.007). In log-rank test restricted to the cases allografted from HLA-identical donors, the difference remained significant with regard to relapse incidence (P=0.039), but not extensive chronic GVHD (P=0.072). No difference in LFS and OS was observed. In conclusion, our study strongly indicates an enhanced graft-versus-leukaemia effect in BSC recipients, which is not expressed in increased survival. The increased chronic GVHD in these patients may contribute, but the relation is complex and not yet understood.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Vigorito AC, Azevedo WM, Marques JF et al. A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies. Bone Marrow Transplant 1998; 22: 1145–1151.

    Article  CAS  PubMed  Google Scholar 

  3. Mahmoud HK, Fahmy OA, Kamel A et al. Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 1999; 24: 355–358.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Powles R, Mehta J, Kulkarni S et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355: 1231–1237.

    Article  CAS  PubMed  Google Scholar 

  6. Heldal D, Tjønnfjord G, Brinch L et al. A randomised study of allogeneic transplantation with stem cells from blood or bone marrow. Bone Marrow Transplant 2000; 25: 1129–1136.

    Article  CAS  PubMed  Google Scholar 

  7. Couban S, Simpson DR, Barnett MJ et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525–1531.

    Article  CAS  PubMed  Google Scholar 

  8. 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 Engl J Med 2001; 3: 175–181.

    Article  Google Scholar 

  9. Champlin RE, Schmitz N, Horowitz MM et al. Blood stem cells compared with bone marrow as source of hematopoietic cells for allogeneic transplantation. Blood 2000; 12: 3702–3709.

    Google Scholar 

  10. Pan L, Delmonte J, Jalonen CK, Ferrara JL . Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood 1996; 86: 4422–4429.

    Google Scholar 

  11. Arpinati M, Green CL, Heimfeld S et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dentritic cells. Blood 2000; 95: 2484–2490.

    CAS  PubMed  Google Scholar 

  12. Majolino J, Saglio G, Scime R et al. High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies. Bone Marrow Transplant 1996; 17: 555–560.

    CAS  PubMed  Google Scholar 

  13. 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 

  14. Scott MA, Gandhi MK, Jestice HK et al. A trend towards an increased incidence of chronic graft-versus-host disease following allogeneic peripheral blood progenitor cell transplantation: a case controlled study. Bone Marrow Transplant 1998; 22: 273–276.

    Article  CAS  PubMed  Google Scholar 

  15. Solano C, Martinez C, Brunet S et al. Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case–control study. Bone Marrow Transplant 1998; 22: 1129–1135.

    Article  CAS  PubMed  Google Scholar 

  16. Ustun C, Arslan O, Beksac M et al. A retrospective comparison of allogeneic peripheral blood stem cell and bone marrow transplantation results from a single center: a focus on the incidence of graft-vs-host disease and relapse. Biol Blood Marrow Transplant 1999; 5: 28–35.

    Article  CAS  PubMed  Google Scholar 

  17. 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 

  18. Vigorito AC, Marques JF, Aranha FJ et al. A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of hematologic malignancies: an update. Haematologica 2001; 86: 665–666.

    CAS  PubMed  Google Scholar 

  19. Mohty M, Kuentz M, Michallet M et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomised study. Blood 2002; 100: 3128–3134.

    Article  CAS  PubMed  Google Scholar 

  20. Flowers MED, Parker PM, Johnston LJ 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 

  21. Marmont AM, Horowitz MM, Gale K et al. T-cell depletion of HLA-identical transplants in leukaemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  22. Elmaagacli AH, Beelen DW, Opalka B et al. The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukaemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow. Blood 1999; 94: 384–389.

    CAS  PubMed  Google Scholar 

  23. Miflin G, Russel NH, Franklin I et al. An analysis of the effect of chronic GvHD on relapse and survival following allogeneic PBSC transplantation. Cytotherapy 2000; 2: 423–428.

    Article  CAS  PubMed  Google Scholar 

  24. Brunet S, Urbano-Ispizua A, Ojeda E et al. Favourable effect of the combination of acute and chronic graft-versus-host disease on the outcome of allogeneic peripheral blood stem cell transplantation for advanced haematological malignancies. Br J Haematol 2001; 114: 544–550.

    Article  CAS  PubMed  Google Scholar 

  25. Uzunel M, Mattsson J, Jaksch M et al. The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia. Blood 2001; 98: 1982–1984.

    Article  CAS  PubMed  Google Scholar 

  26. Schmitz N, Barrett J . Optimizing engraftment-source and dose of stem cells. Semin Hematol 2002; 39: 3–14.

    Article  PubMed  Google Scholar 

  27. Bacigalupo A, Frassoni F, Van Lint MT . Bone marrow or peripheral blood as source of stem cell for allogeneic transplants. Curr Opin Hematol 2000; 7: 343–347.

    Article  CAS  PubMed  Google Scholar 

  28. Bensinger WI, Storb R . Allogeneic peripheral blood stem cell transplantation. Rev Clin Exp Hematol 2001; 5: 67–86.

    Article  CAS  PubMed  Google Scholar 

  29. Russell NH, Byrne JL . Allogeneic transplantation using peripheral blood stem cells. Best Pract Res Clin Haematol 2001; 14: 685–700.

    Article  CAS  PubMed  Google Scholar 

  30. Körbling M, Anderlini P . Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood 2001; 98: 2900–2908.

    Article  PubMed  Google Scholar 

  31. Grimwade D, Walker H, Oliver F et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood 1998; 92: 2322–2333.

    CAS  PubMed  Google Scholar 

  32. Boyer J . Inv(14)(q11;q32.1), t(14;14)(q11;q32.1). Atlas Genet Cytogenet Oncol Haematol 2001. URL: http://www.infobiogen.fr/services/chromcancer/Anomalies/inv14ID2049.html

  33. Heldal D, Brinch L, Tjønnfjord G et al. Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints. Bone Marrow Transplant 2002; 29: 479–486.

    Article  CAS  PubMed  Google Scholar 

  34. Johnsen HE, Knudsen LM . Nordic flow cytometry standards for CD34+ cell enumeration in blood and leukapheresis products: report from the second Nordic Workshop. Nordic Stem Cell Laboratory Group (NSCL-G). J Hematother 1996; 5: 237–245.

    Article  CAS  PubMed  Google Scholar 

  35. Glucksberg H, Storb R, Fefer A et al. Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  36. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  37. Klein JP, Rizzo JD, Zhang M-J, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transplant 2001; 28: 909–915.

    Article  CAS  PubMed  Google Scholar 

  38. Kaplan ED, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  39. Gratwohl A, Hermans J, Niederwieser D et al. Female donors influence transplant-related mortality and relapse incidence in male recipients of sibling blood and marrow transplants. Hematol J 2001; 2: 363–370.

    Article  CAS  PubMed  Google Scholar 

  40. Carlens S, Ringdén O, Remberger M et al. Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant 1998; 22: 755–761.

    Article  CAS  PubMed  Google Scholar 

  41. Zaucha JM, Gooley T, Bensinger WI 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 

  42. Kolb HJ, Socie G, Duell T et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group. Ann Intern Med 1999; 131: 738–744.

    Article  CAS  PubMed  Google Scholar 

  43. Weiden PL, Sullivan KM, Fluornoy N et al. Antileukemic effect of chronic graft-versus-host disease. Contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1533.

    Article  CAS  PubMed  Google Scholar 

  44. Zikos P, van Lint MT, Lamparelli T et al. Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukaemia: favourable impact of chronic graft-versus-host disease on survival and relapse. Haematologica 1998; 83: 896–903.

    CAS  PubMed  Google Scholar 

  45. Ringdén O, Labopin M, Gorin NC et al. Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia? Br J Haematol 2000; 111: 1130–1137.

    Article  PubMed  Google Scholar 

  46. Cavallaro AM, Lilleby K, Majolino I et al. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor. Bone Marrow Transplant 2000; 25: 85–89.

    Article  CAS  PubMed  Google Scholar 

  47. Rowley SD, Donaldson G, Lilleby K et al. Experiences of donors enrolled in a randomised study of allogeneic bone marrow or peripheral blood stem cell transplantation. Blood 2001; 97: 2541–2548.

    Article  CAS  PubMed  Google Scholar 

  48. Couban S, Dranitsaris G, Andreou P et al. Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective. Bone Marrow Transplant 1998; 22: 1199–1205.

    Article  CAS  PubMed  Google Scholar 

  49. Jacobsohn DA, Vogelsang GB . Novel pharmacotherapeutic approaches to prevention and treatment of GVHD. Drugs 2002; 62: 879–889.

    Article  CAS  PubMed  Google Scholar 

  50. Hale G, Jacobs P, Wood L et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant 2000; 26: 69–76.

    Article  CAS  PubMed  Google Scholar 

  51. Di Nicola M, Carlo-Stella C, Magni M et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838–3843.

    Article  CAS  PubMed  Google Scholar 

  52. Frassoni F, Labopin M, Bacigalupo A et al. Expanded mesenchymal stem cells (MSC), co-infused with HLA identical hemopoietic stem cell transplants, reduce acute and chronic graft versus host disease: a matched pair analysis. Bone Marrow Transplant 2002; 29(Suppl. 2): S2 (Abstr. 75).

    Google Scholar 

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Acknowledgements

This study was supported by Bergliot and Sigurd Skaugen's ‘Fond til bekjempelse av kreft’. We also thank the nurses and administrative personnel at Section of Haematology, Medical Department, Rikshospitalet University Hospital, Oslo for their excellent cooperation and patient care, Lill Anny Gunnes Grøseth for CD 34+ cell and T-lymphocyte enumeration and Ellen Finsberg for graphs.

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Authors and Affiliations

  1. Medical Department, Rikshospitalet University Hospital, Oslo, 0027, Norway

    D Heldal, L Brinch, G Tjønnfjord & S A Evensen

  2. Institute of Immunology, Rikshospitalet University Hospital, Oslo, 0027, Norway

    B G Solheim & T Egeland

  3. Department of Surgery, Rikshospitalet University Hospital, Oslo, 0027, Norway

    D Albrechtsen

  4. Section of Biostatistics, Rikshospitalet University Hospital, Oslo, 0027, Norway

    G Aamodt

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Heldal, D., Brinch, L., Tjønnfjord, G. et al. Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study. Bone Marrow Transplant 32, 257–264 (2003). https://doi.org/10.1038/sj.bmt.1704127

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