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Graft-Versus-Host Disease

Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation

Bone Marrow Transplantation volume 47, pages 1564–1568 (2012)Cite this article

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Abstract

The correlation between the incidence of GVHD and the number of infused CD34+ cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor’s blood G-CSF-mobilized CD34+ cell count, and number of infused CD34+ and CD3+ cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 106 CD34+ cells/kg (P=0.05). Interestingly, the number of donor's blood CD34+ cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28–68) at 24-months in the quartile of patients whose donors had the highest CD34+ cell counts versus 24.3% (95% CI: 14–34) in the other patients (P=0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor’s blood CD34+ cell count after G-CSF (HR 2.49; 95% CI: 1.16–5.35, P=0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34+ cells than with the number of infused CD34+ cells.

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References

  1. Stem Cell Trialists' Collaborative Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

    Article  Google Scholar 

  2. Schmitz N, Eapen M, Horowitz MM, Zhang MJ, Klein JP, Rizzo JD et al. Long-term outcome of patients given transplants of mobilized blood or bone marrow: a report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. Blood 2006; 108: 4288–4290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Remberger M, Beelen DW, Fauser A, Basara N, Basu O, Ringdén 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 

  4. Mohty M, Kuentz M, Michallet M, Bourhis JH, Milpied N, Sutton L et al. Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). 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 

  5. Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger 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 

  6. 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 

  7. Dhédin N, Chamakhi I, Perreault C, Roy DC, Sauvageau G, Ducruet T et al. Evidence that donor intrinsic response to G-CSF is the best predictor of acute graft-vs-host disease following allogeneic peripheral blood stem cell transplantation. Exp Hematol 2006; 34: 107–114.

    Article  PubMed  Google Scholar 

  8. Przepiorka D, Anderlini P, Saliba R, Cleary K, Mehra R, Khouri K et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001; 98: 1695–1700.

    Article  CAS  PubMed  Google Scholar 

  9. Carlens S, Ringdén O, Remberger M, Lönnqvist B, Hägglund H, Klaesson S 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 

  10. Hagglund H, Bostrom L, Remberger M, Ljungman P, Nilsson B, Ringdén O . Risk factors for acute graft-versus-host disease in 291 consecutive HLA-identical bone marrow transplant recipients. Bone Marrow Transplant 1995; 16: 747–753.

    CAS  PubMed  Google Scholar 

  11. Nash RA, Pepe MS, Storb R, Longton G, Pettinger M, Anasetti C et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838–1845.

    CAS  PubMed  Google Scholar 

  12. Zaucha JM, Gooley T, Bensinger WI, 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 

  13. 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 

  14. Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S et al. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical sibling. Blood 2002; 100: 724–727.

    Article  CAS  PubMed  Google Scholar 

  15. Perez-Simon JA, Diez-Campelo M, Martino R, Sureda A, Caballero D, Canizo C et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102: 1108–1113.

    Article  CAS  PubMed  Google Scholar 

  16. Dey BR, Shaffer J, Yee AJ, McAfee S, Caron M, Power K et al. Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. Bone Marrow Transplant 2007; 40: 19–27.

    Article  CAS  PubMed  Google Scholar 

  17. Baron F, Maris MB, Storer BE, Sandmaier BM, Panse JP, Chauncey TR et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 2005; 19: 822–828.

    Article  CAS  PubMed  Google Scholar 

  18. Remberger M, Mattsson J, Hassan Z, Karlsson N, LeBlanc K, Omazic B et al. Risk factors for acute graft-versus-host disease grades II-IV after reduces intensity conditioning allogeneic stem cell transplantation with unrelated donors. A single centre study. Bone Marrow Transplant 2008; 41: 399–405.

    Article  CAS  PubMed  Google Scholar 

  19. Michallet M, Le QH, Mohty M, Prébet T, Nicolini F, Boiron JM et al. Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Exp Hematol 2008; 36: 535–544.

    Article  PubMed  Google Scholar 

  20. Bruno B, Rotta M, Patriarca F, Mattei D, Allione B, Carnevale-Schianca F et al. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood 2009; 113: 3375–3382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DJ et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  22. Przepiorka D, Weidorf D, Martin P, Klingemann H-G, Beatty P, Hows J et al. Consensus conference of acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  23. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE 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 

  24. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I . The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother 1996; 5: 213–226.

    Article  CAS  PubMed  Google Scholar 

  25. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR . Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 1998; 15: 61–70.

    Article  Google Scholar 

  26. Heimfeld S, Gooley T, Flowers M, Baron F, Martin P.I, Linenberger M.L et al. Effect of peripheral blood stem cell (PBSC) graft composition on graft versus host disease (GVHD) and mortality after allogeneic transplantation. Blood 2010, 116 (abstract 676).

  27. Heimfeld S . Bone marrow transplantation: how important is CD34 cell dose in HLA-identical stem cell transplantation? Leukemia 2003; 17: 856–858.

    Article  CAS  PubMed  Google Scholar 

  28. 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 1995; 15: 4422–4429.

    Google Scholar 

  29. Arpinati M, Green CL, Heimfeld S, Heuser JE, Anasetti C . Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood 2000; 15: 2484–2490.

    Google Scholar 

  30. Pulsipher MA, Chitphakdithai P, Logan BR, Leitman SF, Anderlini P, Klein JP et al. Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose. Blood 2009; 114: 2606–2616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Collins NH, Gee AP, Durett AG, Kan F, Zhang MJ, Champlin RE et al. The effect of the composition of unrelated donor bone marrow and peripheral blood progenitor cell grafts on transplantation outcomes. Biol Blood Marrow Transplant 2010; 16: 253–262.

    Article  PubMed  Google Scholar 

  32. Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002; 3: 687–694.

    Article  CAS  PubMed  Google Scholar 

  33. Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ . Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 2001; 98: 1289–1297.

    Article  CAS  PubMed  Google Scholar 

  34. Fibbe WE, Pruijt JF, van Kooyk Y, Figdor CG, Opdenakker G, Willemze R . The role of metalloproteinases and adhesion molecules in interleukin-8-induced stem-cell mobilization. Semin Hematol 2000; 37: 19–24.

    Article  CAS  PubMed  Google Scholar 

  35. Anderlini P, Donato M, Chan KW, Huh YO, Gee AP, Lauppe MJ et al. Allogeneic blood progenitor cell collection in normal donors after mobilization with filgrastim: the M.D. Anderson Cancer Center experience. Transfusion 1999; 39: 555–560.

    Article  CAS  PubMed  Google Scholar 

  36. De la Rubia J, Arbona C, de Arriba F, del Cañizo C, Brunet S, Zamora C et al. Spanish Group of Allogeneic Peripheral Blood Stem Cell Transplantation. Analysis of factors associated with low peripheral blood progenitor cell collection in normal donors. Transfusion 2002; 42: 4–9.

    Article  PubMed  Google Scholar 

  37. Ikeda K, Kozuka T, Harada M . Factors for PBPC collection efficiency and collection predictors. Transfus Apher Sci 2004; 31: 245–259.

    Article  PubMed  Google Scholar 

  38. Suzuya H, Watanabe T, Nakagawa R, Watanabe H, Okamoto Y, Onishi T et al. Factors associated with granulocyte colony-stimulating factor-induced peripheral blood stem cell yield in healthy donors. Vox Sang 2005; 89: 229–235.

    Article  CAS  PubMed  Google Scholar 

  39. Ings SJ, Balsa C, Leverett D, Mackinnon S, Linch DC, Watts MJ . Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony-stimulating factor (G-CSF): impact of age, sex, donor weight and type of G-CSF used. Br J Haematol 2006; 34: 517–525.

    Article  Google Scholar 

  40. Vasu S, Leitman SF, Tisdale JF, Hsieh MM, Childs RW, Barrett AJ et al. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population. Blood 2008; 112: 2092–2100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gazitt Y, Liu Q . Plasma levels of SDF-1 and expression of SDF-1 receptor on CD34β cells in mobilized peripheral blood of non-Hodgkin's lymphoma patients. Stem Cells 2001; 19: 37–45.

    Article  CAS  PubMed  Google Scholar 

  42. Moser B, Loetscher P . Lymphocyte traffic control by chemokines. Nat Immunol 2001; 2: 123–128.

    Article  CAS  PubMed  Google Scholar 

  43. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS . Leukocyte migration and graft-versus-host disease. Blood 2005; 105: 4191–4199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wysocki CA, Burkett SB, Panoskaltsis-Mortari A, Kirby SL, Luster AD, McKinnon K et al. Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning. J Immunol 2004; 173: 845–854.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Société Française de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC) for sharing their database and physicians for providing missing data. We thank Dr. Martine Torres for her critical review assistance

Author contributions: N Dhédin designed and performed the research and wrote the paper. M Kuentz performed the research and reviewed the paper. T Prébet, R Peffault De Latour, D Réa, N Piard, JP Jouet, JA Ribeil, R Tabrizi, B Rio, B Lioure, JH Bourrhis, A Sirvent, P Bordigoni, D Blaise, and M Michallet performed the research. S Katsahian analyzed the data. F Norol, P Tiberghien and JP Vernant reviewed the manuscript.

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Authors and Affiliations

  1. Service de Greffe de Moelle, Unité Adolescents et Jeunes Adultes (AJA), Paris, France

    N Dhédin

  2. Unité de Transplantation, Médullaire Institut Paoli Calmettes, Marseille, France

    T Prébet

  3. Service de Greffe de Moelle, Hôpital Saint-Louis, Paris, France

    R Peffault De Latour

  4. Unité de Biostatistique, Hôpital Henri Mondor, Creteil, France

    S Katsahian

  5. Service d’Hématologie, Hôpital Henri Mondor, Creteil, France

    M Kuentz

  6. Etablissement Français du Sang, Pays de la Loire-Site d’Angers, Angers, France

    N Piard

  7. Unité de Thérapie Cellulaire et de Clinique Transfusionnelle, Hôpital Saint-Louis, Paris, France

    D Réa

  8. Centre de Transfusion Sanguine, Groupe, Hospitalier, Pitié-Salpêtrière, Paris, France

    F Norol

  9. Service des Maladies du Sang, Hôpital Claude Huriez CHRU, Lille, France

    J P Jouet

  10. Département de biothérapie, Groupe Hospitalier Necker-Enfants Malades, Paris, France

    J A Ribeil

  11. Service des Maladies du Sang, GH du Haut Levêque, Pessac, France

    R Tabrizi

  12. Service d’Hématologie, Hôtel Dieu, Paris, France

    B Rio

  13. Service d’Onco-Hématologie, CHU Hautepierre, Strasbourg, France

    B Lioure

  14. Unité de Thérapie Cellulaire, Etablissement Français du sang, Bourgogne Franche-Comté, Besancon, France,

    P Tiberghien

  15. Service d’Hématologie, Institut Gustave Roussy, Villejuif, France

    J H Bourhis

  16. Service d’Hématologie et d’Oncologie Médicale Hôpital Lapeyronie CHU Avenue du Doyen Giraud, Montpellier, France

    A Sirvent

  17. Unité de Transplantation Médullaire, Hôpital Brabois- Hôpital d’Enfants, Nancy, France

    P Bordigoni

  18. Unité de Transplantation Médullaire, Institut Paoli Calmettes, Marseille, France

    D Blaise

  19. Service d’Hématologie Pavillon E, Hôpital Edouard Herriot 5, Lyon, France

    M Michallet

  20. Service d’Hématologie GH Pitié-Salpêtrière, Paris, France

    J P Vernant

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Dhédin, N., Prébet, T., De Latour, R. et al. Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation. Bone Marrow Transplant 47, 1564–1568 (2012). https://doi.org/10.1038/bmt.2012.75

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