Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

Prognostic value of response after upfront therapy for acute GVHD

Bone Marrow Transplantation volume 47, pages 125–131 (2012)Cite this article

Abstract

One challenge in designing clinical trials for treatment of acute GVHD (aGVHD) is the lack of an established standardized end point to measure the success of therapies. To facilitate assessment of end points in clinical trials for treatment of aGVHD in the current allo-SCT era, a national workshop was recently organized. In this study, which was presented at the workshop, we evaluated the prognostic value of response to upfront therapy in a cohort of 83 patients who had been enrolled on two clinical trials testing novel therapies for aGVHD at our institution. Our results indicate that patients whose aGVHD has a CR or PR by day 28 after initiation of systemic therapy have a significantly lower 6-month cumulative incidence of non-relapse mortality (NRM) (16%) than patients whose aGVHD did not respond to therapy by day 28 (48%, P=0.005). Multivariate analysis based on the Cox proportional hazards regression analysis showed that the impact of response on NRM is independent of patient and aGVHD characteristics. Our data confirm the validity of using day-28 response as a primary end point in clinical trials for upfront therapy for aGVHD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Martin PJ, Bachier CR, Klingemann HG, McCarthy PL, Szabolcs P, Uberti JP et al. Endpoints for clinical trials testing treatment of acute graft-versus-host disease: a joint statement. Biol Blood Marrow Transplant 2009; 15: 777–784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Martin PJ, Nash RA . Pitfalls in the design of clinical trials for prevention or treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant 2006; 12 (Suppl 2): 31–36.

    Article  PubMed  Google Scholar 

  3. Alousi AM, Weisdorf DJ, Logan BR, Bolanos-Meade J, Carter S, Difronzo N et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood 2009; 114: 511–517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Couriel DR, Saliba R, de Lima M, Giralt S, Andersson B, Khouri I et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant 2009; 15: 1555–1562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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 

  6. Akaike H . A new look at the statistical model identification. Transactions on Automatic Control 1974; 19: 716–723.

    Article  Google Scholar 

  7. MacMillan ML, DeFor TE, Weisdorf DJ . The best endpoint for acute GVHD treatment trials. Blood 2010; 115: 5412–5417.

    Article  CAS  PubMed  Google Scholar 

  8. Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolanos-Meade J et al. Graft-versus-host disease treatment: predictors of survival. Biol Blood Marrow Transplant 2010; 16: 1693–1699.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cahn J-Y, Klein JP, Lee SJ, Milpied N, Blaise D, Antin JH et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood 2005; 106: 1495–1500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Leisenring WM, Martin PJ, Petersdorf EW, Regan AE, Aboulhosn N, Stern JM et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood 2006; 108: 749–755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. MacMillan ML, Weisdorf DJ, Wagner JE, DeFor TE, Burns LJ, Ramsay NK et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant 2002; 8: 387–394.

    Article  CAS  PubMed  Google Scholar 

  12. Westin JR, Saliba RM, de Lima M, Alousi A, Hosing C, Qazilbash MH et al. Risk factors for response after initial therapy for acute graft-versus-host-disease (aGVHD). ASH Annu Meeting Abstracts 2007; 110: 5015.

    Google Scholar 

  13. Pasquini MC . Impact of graft-versus-host disease on survival. Best Pract Res Clin Haematol 2008; 21: 193–204.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge our patients and clinical staff, without whom this research would not have been possible.

Author information

Authors and Affiliations

  1. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R M Saliba, G Rondon, G-J Okoroji, R E Champlin & A M Alousi

  2. University of Michigan Comprehensive Cancer Center, Bone Marrow Transplant Program, Ann Arbor, MI, USA

    D R Couriel

  3. Division of Hematologic Oncology, Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    S Giralt

  4. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    A Rashid

Authors
  1. R M Saliba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D R Couriel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Giralt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Rondon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G-J Okoroji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Rashid
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R E Champlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A M Alousi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R M Saliba.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

The results of this work have been partially presented at an acute GVHD workshop in Bethesda, MD, in 2009.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saliba, R., Couriel, D., Giralt, S. et al. Prognostic value of response after upfront therapy for acute GVHD. Bone Marrow Transplant 47, 125–131 (2012). https://doi.org/10.1038/bmt.2011.41

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.41

Keywords

This article is cited by

Search

Advanced search

Quick links