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Graft-versus-host Disease

Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival

Bone Marrow Transplantation volume 49, pages 122–125 (2014)Cite this article

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Abstract

We studied whether early CsA trough levels were associated with the risk of acute GVHD in 337 patients after either sibling PBSC or double umbilical cord blood transplantation. All patients, regardless of donor type, started CsA at a dose of 5 mg/kg i.v. divided twice daily, targeting trough concentrations 200–400 ng/mL. The CsA level was studied by a weighted average method calculated by giving 70% of the weight to the level that was measured just before the onset of the event or day +30. We found that higher weighted average CsA trough levels early post transplantation contributed to lower risk of acute GVHD, and lower non-relapse and overall mortality. Thus, our data support close monitoring with active adjustments of CsA dosing to maintain therapeutic CsA levels in the first weeks of allo-HCT. In patients who are near or even modestly above the CsA target trough level, in the absence of CsA-related toxicity, dose reduction should be cautious to avoid subtherapeutic drug levels resulting in higher risk of acute GVHD.

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References

  1. Billingham RE, Brent L . A simple method for inducing tolerance of skin homografts in mice. Transplant Bull 1957; 4: 67–71.

    CAS  PubMed  Google Scholar 

  2. Yee GC, Self SG, McGuire TR, Carlin J, Sanders JE, Deeg HJ . Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation. N Engl J Med 1988; 319: 65–70.

    Article  CAS  Google Scholar 

  3. Lamparelli T, Van Lint MT, Gualandi F, Occhini D, Barbanti M, Sacchi N et al. Bone marrow transplantation for chronic myeloid leukemia (CML) from unrelated and sibling donors: single center experience. Bone Marrow Transplant 1997; 20: 1057–1062.

    Article  CAS  Google Scholar 

  4. Kedmi M, Dray L, Grisariu S, Resnick IB, Stepensky P, Aker M et al. The effect of cyclosporine initiation time on the outcome of matched allogeneic stem-cell transplantation following fludarabine-based conditioning. Transpl Int 2012; 25: 1241–1247.

    Article  CAS  Google Scholar 

  5. Ram R, Storer B, Mielcarek M, Sandmaier BM, Maloney DG, Martin PJ et al. Association between calcineurin inhibitor blood concentrations and outcomes after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18: 414–422.

    Article  CAS  Google Scholar 

  6. Malard F, Szydlo RM, Brissot E, Chevallier P, Guillaume T, Delaunay J et al. Impact of cyclosporine-A concentration on the incidence of severe acute graft-versus-host disease after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2010; 16: 28–34.

    Article  CAS  Google Scholar 

  7. Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.

    Article  CAS  Google Scholar 

  8. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.

    Article  CAS  Google Scholar 

  9. Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA et al. Allogeneic hematopoietic cell transplantation for hematological malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693–4699.

    Article  CAS  Google Scholar 

  10. Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M et al. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood 2012; 119: 4083–4090.

    Article  CAS  Google Scholar 

  11. Adkins JC, Peters DH, Markham A . Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies. Drugs 1997; 53: 1005–1037.

    CAS  PubMed  Google Scholar 

  12. 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  Google Scholar 

  13. Cox DR . Regression models and life tables. J Royal Stat Soc B. 1972; 34: 187–220.

    Google Scholar 

  14. Prentice RL, Williams BJ, Peterson AV . On the regression analysis of multivariate failure time data. Biometrika 1981; 68: 373–379.

    Article  Google Scholar 

  15. Tarone RE, Ware J . Tests for trend in life table analysis. Biometrika 1975; 62: 679–687.

    Article  Google Scholar 

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

    Article  Google Scholar 

  17. Blazar BR, Murphy WJ, Abedi M . Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol 2012; 12: 443–458.

    Article  CAS  Google Scholar 

  18. MacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 2009; 113: 2410–2415.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by grants from the National Cancer Institute PO1-CA65493 (CGB, BRB and TED) and Leukemia and Lymphoma Society Scholar in Clinical Research Award (CGB).

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  1. University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA

    J R Rogosheske, A D Fargen, T E DeFor, E Warlick, M Arora, B R Blazar, D J Weisdorf & C G Brunstein

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  1. J R Rogosheske
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  2. A D Fargen
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  3. T E DeFor
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  4. E Warlick
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  5. M Arora
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  7. D J Weisdorf
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  8. C G Brunstein
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Correspondence to C G Brunstein.

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Rogosheske, J., Fargen, A., DeFor, T. et al. Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival. Bone Marrow Transplant 49, 122–125 (2014). https://doi.org/10.1038/bmt.2013.139

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  • DOI: https://doi.org/10.1038/bmt.2013.139

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