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Graft-versus-host Disease

Eosinophilia predicts better overall survival after acute graft-versus-host-disease

Bone Marrow Transplantation volume 45, pages 371–377 (2010)Cite this article

Abstract

The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P=0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P=0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P=0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P=0.03) and lower NRM (P=0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P=0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.

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References

  1. Rothenberg ME . Eosinophilia. N Engl J Med 1998; 338: 1592–1600.

    Article  CAS  PubMed  Google Scholar 

  2. Kalaycioglu ME, Bolwell BJ . Eosinophilia after allogeneic bone marrow transplantation using the busulfan and cyclophosphamide preparative regimen. Bone Marrow Transplant 1994; 14: 113–115.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  5. Basara N, Kiehl MG, Fauser AA . Eosinophilia indicates the evolution to acute graft-versus-host disease. Blood 2002; 100: 3055.

    Article  CAS  PubMed  Google Scholar 

  6. McNeel D, Rubio MT, Damaj G, Emile JF, Belanger C, Varet B et al. Hypereosinophilia as a presenting sign of acute graft-versus-host disease after allogeneic bone marrow transplantation. Transplantation 2002; 74: 1797–1800.

    Article  CAS  PubMed  Google Scholar 

  7. Sato T, Kobayashi R, Nakajima M, Iguchi A, Ariga T . Significance of eosinophilia after stem cell transplantation as a possible prognostic marker for favorable outcome. Bone Marrow Transplant 2005; 36: 985–991.

    Article  CAS  PubMed  Google Scholar 

  8. Aisa Y, Mori T, Nakazato T, Shimizu T, Yamazaki R, Ikeda Y et al. Blood eosinophilia as a marker of favorable outcome after allogeneic stem cell transplantation. Transpl Int 2007; 20: 761–770.

    Article  CAS  PubMed  Google Scholar 

  9. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  10. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  11. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B and HLA-DR matched unrelated donors. Blood 2002; 99: 4200–4206.

    Article  CAS  PubMed  Google Scholar 

  13. Morishima Y, Yabe T, Matsuo K, Kashiwase K, Inoko H, Saji H et al. Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor. Biol Blood Marrow Transplant 2007; 13: 315–328.

    Article  CAS  PubMed  Google Scholar 

  14. Lampinen M, Carlson M, Hakansson LD, Venge P . Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy 2004; 59: 793–805.

    Article  CAS  PubMed  Google Scholar 

  15. Ball LM, Egeler RM . Acute GvHD: pathogenesis and classification. Bone Marrow Transplant 2008; 41 (Suppl 2): S58–S64.

    Article  CAS  PubMed  Google Scholar 

  16. Morris ES, Hill GR . Advances in the understanding of acute graft-versus-host disease. Br J Haematol 2007; 137: 3–19.

    Article  CAS  PubMed  Google Scholar 

  17. Ferrara JL, Levy R, Chao NJ . Pathophysiologic mechanisms of acute graft-vs-host disease. Biol Blood Marrow Transplant 1999; 5: 347–356.

    Article  CAS  PubMed  Google Scholar 

  18. Imamura M, Tsutsumi Y, Miura Y, Toubai T, Tanaka J . Immune reconstitution and tolerance after allogeneic hematopoietic stem cell transplantation. Hematology 2003; 8: 19–26.

    Article  CAS  PubMed  Google Scholar 

  19. Tanaka J, Imamura M, Kasai M, Hashino S, Kobayashi S, Noto S et al. The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease. Bone Marrow Transplant 1997; 19: 571–576.

    Article  CAS  PubMed  Google Scholar 

  20. Imamura M, Hashino S, Kobayashi H, Kubayashi S, Hirano S, Minagawa T et al. Serum cytokine levels in bone marrow transplantation: synergistic interaction of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha in graft-versus-host disease. Bone Marrow Transplant 1994; 13: 745–751.

    CAS  PubMed  Google Scholar 

  21. Petersen SL, Madsen HO, Ryder LP, Svejgaard A, Dickmeiss E, Vindelov LL . Cytokine gene expression in peripheral blood mononuclear cells and alloreactivity in hematopoietic cell transplantation with nonmyeloablative conditioning. Biol Blood Marrow Transplant 2006; 12: 48–60.

    Article  CAS  PubMed  Google Scholar 

  22. Pan L, Delmonte Jr 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; 86: 4422–4429.

    CAS  PubMed  Google Scholar 

  23. Fowler DH, Kurasawa K, Smith R, Eckhaus MA, Gress RE . Donor CD4-enriched cells of Th2 cytokine phenotype regulate graft-versus-host disease without impairing allogeneic engraftment in sublethally irradiated mice. Blood 1994; 84: 3540–3549.

    CAS  PubMed  Google Scholar 

  24. Weston LE, Geczy AF, Briscoe H . Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD. Bone Marrow Transplant 2006; 37: 207–212.

    Article  CAS  PubMed  Google Scholar 

  25. Takabayashi M, Kanamori H, Takasaki H, Yamaji S, Koharazawa H, Taguchi J et al. A possible association between the presence of interleukin-4-secreting cells and a reduction in the risk of acute graft-versus-host disease. Exp Hematol 2005; 33: 251–257.

    Article  CAS  PubMed  Google Scholar 

  26. Adachi T, Alam R . The mechanism of IL-5 signal transduction. Am J Physiol 1998; 275: C623–C633.

    Article  CAS  PubMed  Google Scholar 

  27. Sloand EM, Kim S, Maciejewski JP, Van Rhee F, Chaudhuri A, Barrett J 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 

  28. Khoury HJ, Loberiza Jr FR, Ringden O, Barrett AJ, Bolwell BJ, Cahn JY et al. Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation. Blood 2006; 107: 1712–1716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ho VT, Mirza NQ, Junco Dd D, Okamura T, Przepiorka D . The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis. Bone Marrow Transplant 2003; 32: 771–775.

    Article  CAS  PubMed  Google Scholar 

  30. Ringden O, Labopin M, Gorin NC, Le Blanc K, Rocha V, Gluckman E et al. Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2004; 22: 416–423.

    Article  CAS  PubMed  Google Scholar 

  31. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864.

    Article  CAS  PubMed  Google Scholar 

  32. Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990; 75: 1024–1030.

    CAS  PubMed  Google Scholar 

  33. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling. Bone Marrow Transplant 2001; 28: 1001–1011.

    Article  CAS  PubMed  Google Scholar 

  34. Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 1990; 76: 1464–1472.

    CAS  PubMed  Google Scholar 

  35. Messina C, Faraci M, de Fazio V, Dini G, Calo MP, Calore E . Prevention and treatment of acute GvHD. Bone Marrow Transplant 2008; 41 (Suppl 2): S65–S70.

    Article  CAS  PubMed  Google Scholar 

  36. Gorak E, Geller N, Srinivasan R, Espinoza-Delgado I, Donohue T, Barrett AJ et al. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transplant 2005; 11: 542–550.

    Article  PubMed  Google Scholar 

  37. Cooke KR, Yanik G . Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease? Bone Marrow Transplant 2004; 34: 753–765.

    Article  CAS  PubMed  Google Scholar 

  38. Majhail NS, Parks K, Defor TE, Weisdorf DJ . Diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes. Biol Blood Marrow Transplant 2006; 12: 1038–1046.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    N Imahashi, K Miyamura, A Seto, K Watanabe, M Yanagisawa, S Nishiwaki, M Shinba, T Yasuda, Y Kuwatsuka, S Terakura & Y Kodera

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  1. N Imahashi
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  2. K Miyamura
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Correspondence to N Imahashi.

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Imahashi, N., Miyamura, K., Seto, A. et al. Eosinophilia predicts better overall survival after acute graft-versus-host-disease. Bone Marrow Transplant 45, 371–377 (2010). https://doi.org/10.1038/bmt.2009.135

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