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Immune Recovery

Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells

Abstract

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs cml) after transplant, and had a cd4:cd8 ratio >1 with a median CD4+ t cell value >400/μl 1 year after transplant. development of acute graft-versus-host disease (gvhd) did not affect cd4:cd8 ratios but patients who experienced acute gvhd >grade I had lower CD4+ and CD8+ t cell numbers at all time points. however, after excluding patients with gvhd >grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease. Bone Marrow Transplantation (2000) 26, 1325–1331.

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References

  1. Korbling M, Przepiorka D, Huh YO et al. Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma – potential advantage of blood over marrow allografts Blood 1995 85: 1659–1665

    CAS  PubMed  Google Scholar 

  2. Bensinger WI, Weaver CH, Appelbaum FR et al. Transplantation of allogeneic peripheral blood stem cells mobilised by recombinant human granulocyte colony-stimulating factor Blood 1995 85: 1655–1658

    CAS  PubMed  Google Scholar 

  3. Schmitz N, Dreger P, Suttorp M et al. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor) Blood 1995 85: 1666–1672

    CAS  PubMed  Google Scholar 

  4. Ottinger HD, Beelen DW, Scheulen B et al. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow Blood 1996 88: 2775–2779

    CAS  PubMed  Google Scholar 

  5. Charbonnier A, Sainty D, Faucher C et al. Immune reconstitution after blood cell transplantation Hematol Cell Ther 1997 39: 261–264

    Article  CAS  Google Scholar 

  6. Bensinger WI, Buckner CD, Anasetti C et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome Blood 1996 88: 2787–2793

    CAS  Google Scholar 

  7. Bjorkstrand BB, Ljungman P, Svensson H et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from European Group for Blood and Marrow Transplantation Blood 1996 88: 4711–4718

    CAS  Google Scholar 

  8. Cavo M, Bandini G, Benni M et al. High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma Bone Marrow Transplant 1998 22: 27–32

    Article  CAS  Google Scholar 

  9. Majolino I, Corradini P, Scimè R et al. Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma Bone Marrow Transplant 1998 22: 449–455

    Article  CAS  Google Scholar 

  10. Gahrton G, Svensson H, Apperley J et al. Progress in allogeneic hematopoietic stem-cell transplantation for multiple myeloma Bone Marrow Transplant 2000 25: (Suppl. 1) 140 (Abstr.)

    Google Scholar 

  11. Lemoli RM, Bandini G, Leopardi G et al. Allogeneic peripheral blood stem cell transplantation in patients with early-phase hematologic malignancy: a retrospective comparison of short-term outcome with bone marrow transplantation Haematologica 1998 83: 48–55

    CAS  PubMed  Google Scholar 

  12. Bonini A, Bandini G, Rosti G et al. Big Bu/Cy is associated with a favorable long-term outcome in patients allotransplanted for chronic myelogenous leukemia in chronic phase Bone Marrow Transplant 1998 21: 1085–1089

    Article  CAS  Google Scholar 

  13. Przepiorka D, Weisdorf D, Martin P et al. Consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Talmadge JE, Reed E, Ino K et al. Rapid immunologic reconstitution following transplantation with mobilized peripheral blood stem cells as compared to bone marrow Bone Marrow Transplant 1997 19: 161–172

    Article  CAS  Google Scholar 

  16. Behringer D, Bertz H, Schmoor C et al. Quantitative lymphocyte subset reconstitution after allogeneic hematopoietic transplantation from matched related donors with CD34+ selected PBPC grafts, unselected PBPC or BM grafts Bone Marrow Transplant 1999 24: 295–302

    Article  CAS  Google Scholar 

  17. Martinez 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  CAS  Google Scholar 

  18. Pavletic ZS, Joshi SS, Pirruccello SJ et al. Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies Bone Marrow Transplant 1998 21: 33–41

    Article  CAS  Google Scholar 

  19. Douek DC, Vescio RA, Betts MR et al. Assessment of thymic output in adults after haematopoietic stem cell transplantation and prediction of T-cell reconstitution Lancet 2000 355: 1875–1881

    Article  CAS  Google Scholar 

  20. Roberts MM, To LB, Gillis D et al. Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation Bone Marrow Transplant 1993 12: 469–475

    CAS  PubMed  Google Scholar 

  21. Lin MT, Tseng LH, Frangoul H et al. Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation Blood 2000 95: 3832–3839

    CAS  PubMed  Google Scholar 

  22. Metha J, Singhal S . Graft-versus-myeloma Bone Marrow Transplant 1998 22: 835–843

    Article  Google Scholar 

  23. Rondelli D, Bandini G, Cavo M et al. Discrepancy between serological complete remission and concomitant new bone lytic lesions after infusion of escalating low doses of donor lymphocytes in multiple myeloma: a case report Bone Marrow Transplant 1999 24: 685–687

    Article  CAS  Google Scholar 

  24. Rondelli D, Raspadori D, Anasetti C et al. Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF mobilized peripheral blood cells Bone Marrow Transplant 1998 22: 631–637

    Article  CAS  Google Scholar 

  25. Sloand EM, Kim S, Maciejewski JP et al. Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo Blood 2000 95: 2269–2274

    CAS  PubMed  Google Scholar 

  26. Mielcarek M, Martin PJ, Torok-Storb B . Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells Blood 1997 89: 1629–1634

    CAS  PubMed  Google Scholar 

  27. Boneberg EM, Hareng LH, Gantner F et al. Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ Blood 2000 95: 270–276

    CAS  PubMed  Google Scholar 

  28. Nawa Y, Teshima T, Sunami K et al. G-CSF reduces IFN-γ and IL-4 production by T cells after allogeneic stimulation by indirectly modulating monocyte function Bone Marrow Transplant 2000 25: 1035–1040

    Article  CAS  Google Scholar 

  29. Arpinati M, Green CL, Heimfeld S, Anasetti C . G-CSF mobilizes T helper 2-inducing dendritic cells Blood 2000 95: 2269–2274

    Google Scholar 

  30. Shlomchik WD, Couzens MS, Tang CB et al. Prevention of graft-versus-host disease by inactivation of host antigen-presenting cells Science 1999 285: 412–415

    Article  CAS  Google Scholar 

  31. Waller EK, Lynn MJ, Boyer M et al. Survival after allogeneic bone marrow transplantation (BMT) is predicted by the number of transplanted donor CD34+ cells and donor dendritic cell progenitors (DCPs) Blood 1998 92: (Suppl. 1) 2041 (Abstr.)

    Google Scholar 

  32. Reddy V, Hill GR, Pan L et al. G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient Transplantation 2000 69: 691–693

    Article  CAS  Google Scholar 

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Acknowledgements

This work was partially supported by Fondazione Cassa di Risparmio di Bologna (Bologna, Italy) and MURST (Rome, Italy).

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Rondelli, D., Re, F., Bandini, G. et al. Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells. Bone Marrow Transplant 26, 1325–1331 (2000). https://doi.org/10.1038/sj.bmt.1702709

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