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Post-Transplant Events

Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning

Bone Marrow Transplantation volume 45, pages 689–693 (2010)Cite this article

Abstract

The role of conditioning intensity on occurrence of thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplantation (HCT) has remained unclear thus far. Here, we retrospectively compared the incidence of TMA in patients given allogeneic hematopoietic stem cells after either nonmyeloablative (n=176) or high-dose (n=111) conditioning. The 1-year cumulative incidence of TMA was 13% in nonmyeloablative recipients versus 15% in high-dose conditioning recipients (P=0.5). In multivariate Cox analysis, occurrence of grade 3–4 acute graft-versus-host disease (GVHD) (hazard ratio (HR)=2.3, P<0.001), older age (HR=1.01, P=0.045), and unrelated donors (HR=1.6, P=0.01) were each associated with a higher risk of TMA, whereas nonmyeloablative conditioning was associated with a lower risk of TMA (HR=0.6, P=0.01). We conclude that acute GVHD, age, donor type, and conditioning intensity might have a role in the physiopathology of TMA after allogeneic HCT.

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References

  1. Batts ED, Lazarus HM . Diagnosis and treatment of transplantation-associated thrombotic microangiopathy: real progress or are we still waiting? Bone Marrow Transplant 2007; 40: 709–719.

    Article  CAS  PubMed  Google Scholar 

  2. Kojouri K, George JN . Thrombotic microangiopathy following allogeneic hematopoietic stem cell transplantation. Curr Opin Oncol 2007; 19: 148–154.

    Article  PubMed  Google Scholar 

  3. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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 

  4. Baron F, Storb R, Storer BE, Maris MB, Niederwieser D, Shizuru JA et al. Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning after failed myeloablative hematopoietic cell transplantation. J Clin Oncol 2006; 24: 4150–4157.

    Article  PubMed  Google Scholar 

  5. Baron F, Sandmaier BM, Storer BE, Maris MB, Langston AA, Lange T et al. Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning. Biol Blood Marrow Transplant 2007; 13: 1041–1048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Maris MB, Sandmaier BM, Storer BE, Maloney DG, Shizuru JA, Agura E et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant 2006; 12: 454–465.

    Article  CAS  PubMed  Google Scholar 

  7. Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993–2003.

    Article  PubMed  Google Scholar 

  8. Baron F, Petersdorf EW, Gooley T, Sandmaier BM, Malkki M, Chauncey TR et al. What is the role for donor natural killer cells after nonmyeloablative conditioning? Biol Blood Marrow Transplant 2009; 15: 580–588.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Baron F, Sandmaier BM . Nonmyeloablative Transplantation. In: Soiffer RJ (ed). Hematopoietic Stem Cell Transplantation. Humana Press: Totowa, 2008, pp 349–374.

    Chapter  Google Scholar 

  10. Castermans E, Baron F, Willems E, Schaaf-Lafontaine N, Meuris N, Gothot A et al. Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning. Haematologica 2008; 93: 240–247.

    Article  PubMed  Google Scholar 

  11. Baron F, Baudoux E, Frere P, Tourqui S, Schaaf-Lafontaine N, Herens C et al. Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC. Bone Marrow Transplant 2003; 32: 829–834.

    Article  CAS  PubMed  Google Scholar 

  12. Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 571–575.

    Article  PubMed  Google Scholar 

  13. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  14. Shimoni A, Yeshurun M, Hardan I, Avigdor A, Ben Bassat I, Nagler A . Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced. Biol Blood Marrow Transplant 2004; 10: 484–493.

    Article  PubMed  Google Scholar 

  15. Nakamae H, Yamane T, Hasegawa T, Nakamae M, Terada Y, Hagihara K et al. Risk factor analysis for thrombotic microangiopathy after reduced-intensity or myeloablative allogeneic hematopoietic stem cell transplantation. Am J Hematol 2006; 81: 525–531.

    Article  PubMed  Google Scholar 

  16. Holler E, Kolb HJ, Hiller E, Mraz W, Lehmacher W, Gleixner B et al. Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation. Blood 1989; 73: 2018–2024.

    CAS  PubMed  Google Scholar 

  17. Roy V, Rizvi MA, Vesely SK, George JN . Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes. Bone Marrow Transplant 2001; 27: 641–646.

    Article  CAS  PubMed  Google Scholar 

  18. Daly AS, Hasegawa WS, Lipton JH, Messner HA, Kiss TL . Transplantation-associated thrombotic microangiopathy is associated with transplantation from unrelated donors, acute graft-versus-host disease and venoocclusive disease of the liver. Transfus Apher Sci 2002; 27: 3–12.

    Article  PubMed  Google Scholar 

  19. Uderzo C, Bonanomi S, Busca A, Renoldi M, Ferrari P, Iacobelli M et al. Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Transplantation 2006; 82: 638–644.

    Article  PubMed  Google Scholar 

  20. Ruutu T, Hermans J, Niederwieser D, Gratwohl A, Kiehl M, Volin L et al. Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2002; 118: 1112–1119.

    Article  PubMed  Google Scholar 

  21. Biedermann BC, Sahner S, Gregor M, Tsakiris DA, Jeanneret C, Pober JS et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet 2002; 359: 2078–2083.

    Article  PubMed  Google Scholar 

  22. George JN, Li X, McMinn JR, Terrell DR, Vesely SK, Selby GB . Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion 2004; 44: 294–304.

    Article  PubMed  Google Scholar 

  23. Hale GA, Bowman LC, Rochester RJ, Benaim E, Heslop HE, Krance RA et al. Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children. Biol Blood Marrow Transplant 2005; 11: 912–920.

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to physicians, physicians' assistants, and clinical staff for their dedicated care of the patients. FB is a senior research associate and YB a research director of the National Fund for Scientific Research (FRS-FNRS), Belgium. The study was in part supported by funds from the FNRS, the anti-Cancer Center from the University of Liège, and by the Belgian Federation against Cancer (FBC).

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  1. E Willems and F Baron: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, University of Liège and CHU of Liège, Liège, Belgium

    E Willems, F Baron, P Frère, G Fillet & Y Beguin

  2. Department of Infection, Immunity and Inflammation, Giga-Research, Section of Hematology, University of Liège, Liège, Belgium

    E Willems, F Baron, P Frère, G Fillet & Y Beguin

  3. Department of Statistics, University of Liège, Liège, Belgium

    L Seidel

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  1. E Willems
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Correspondence to F Baron.

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Willems, E., Baron, F., Seidel, L. et al. Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning. Bone Marrow Transplant 45, 689–693 (2010). https://doi.org/10.1038/bmt.2009.230

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