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

Treatment of refractory chronic GVHD with rituximab: a GITMO study

Bone Marrow Transplantation volume 40, pages 273–277 (2007)Cite this article

Abstract

The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22–61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2–116), the median number of failed treatment lines was 3 (range 1 to ⩾6) and the median follow-up after Rituximab was 11 months (1–88). Overall response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%), liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3, vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the study period 8/38 died: causes of death were cGVHD progression (n=3), disease relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival is currently 76%. We confirm that Rituximab is effective in over 50% of patients with refractory cGVHD and may have a beneficial impact on survival.

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

Similar content being viewed by others

References

  1. Lee SJ, Vogelsang G, Gilman A, Weisdorf DJ, Pavletic S, Antin JH et al. A survey of diagnosis, management and grading of Chronic GVHD. Biol Blood Marrow Transplant 2002; 8: 32–39.

    Article  Google Scholar 

  2. Goerner M, Gooley T, Flowers ME, Sullivan KM, Kiem HP, Sanders JE et al. Storb R. Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic aplastic or refractory anemias. Biol Blood Marrow Transplant 2002; 8: 47–56.

    Article  CAS  Google Scholar 

  3. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood 2002; 100: 48–51.

    Article  CAS  Google Scholar 

  4. Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D . Rituximab for steroid-refractory chronic graft-vs.-host disease. Blood 2006; 108: 756–762.

    Article  CAS  Google Scholar 

  5. Zaja F, Vianelli N, Sperotto A, De Vita S, Iacona I, Zaccaria A et al. B-cell compartment as the selective target for the treatment of immune thrombocytopenias. Haematologica 2003; 88: 538–546.

    PubMed  Google Scholar 

  6. Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood 2003; 101: 3857–3861.

    Article  CAS  Google Scholar 

  7. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004; 350: 2572–2581.

    Article  CAS  Google Scholar 

  8. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D, De Marchi D et al. Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 2003; 101: 3827–3834.

    Article  CAS  Google Scholar 

  9. Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ et al. Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 2004; 50: 3580–3590.

    Article  CAS  Google Scholar 

  10. Fakhouri F, Vernant JP, Veyradier A, Wolf M, Kaplanski G, Binaut R et al. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood 2005; 106: 1932–1937.

    Article  CAS  Google Scholar 

  11. Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.

    Article  CAS  Google Scholar 

  12. Zaja F, Russo D, Fuga G, Perella G, Baccarani M . Rituximab for myasthenia gravis developing after bone marrow transplant. Neurology 2000; 55: 1062–1063.

    Article  CAS  Google Scholar 

  13. Abrahamsen IW, Somme S, Heldal D, Egeland T, Kvale D, Tjonnfjord GE . Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease. Haematologica 2005; 90: 86–93.

    PubMed  Google Scholar 

  14. Patriarca F, Skert C, Sperotto A, Zaja F, Falleti E, Mestroni R et al. The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-versus-host disease and immune recovery. Exp Hematol 2006; 34: 389–396.

    Article  CAS  Google Scholar 

  15. Ratanatharathorn V, Ayash L, Reynolds C, Silver S, Reddy P, Becker M et al. Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody. Biol Blood Marrow Transplant 2003; 9: 505–511.

    Article  CAS  Google Scholar 

  16. Canninga-van Dijk MR, van der Straaten HM, Fijnheer R, Sanders CJ, van den Tweel JG, Verdonck LF . Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease. Blood 2004; 15: 2603–2606.

    Article  Google Scholar 

  17. Okamoto M, Okano A, Akamatsu S, Ashihara E, Inaba T, Takenaka H et al. Rituximab is effective for steroid-refractory sclerodermatous chronic graft-versus-host disease. Leukemia 2006; 20: 172–173.

    Article  CAS  Google Scholar 

  18. Sato S, Fujimoto M, Hasegawa M, Takehara K . Altered blood B lymphocyte homeostasis in systemic sclerosis. Expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum 2004; 50: 1918–1927.

    Article  Google Scholar 

  19. Famularo G, Giacomelli R, Alesse E, Cifone MG, Morrone S, Boirivant M et al. Polyclonal B lymphocyte activation in progressive systemic sclerosis. J Clin Lab Immunol 1989; 29: 59–63.

    CAS  PubMed  Google Scholar 

  20. Hasegawa M, Hamaguchi Y, Yanaba K, Bouaziz JD, Uchida J, Fujimoto M et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol 2006; 169: 954–966.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank AIL Pordenone for their kind support.

Author information

Authors and Affiliations

  1. Clinica Ematologica DIRM, Azienda Ospedaliera Universitaria, Udine, Italy

    F Zaja, F Patriarca, C Filì, A Sperotto & R Fanin

  2. Divisione di Ematologia, Ospedale San Martino, Genova, Italy

    A Bacigalupo & M T Van Lint

  3. Istituto di Ematologia ed Oncologia Medica L. ed A. Seragnoli, Bologna, Italy

    M Stanzani & F Bonifazi

  4. Divisione di Ematologia e TMO, Azienda Cervello, Palermo, Italy

    R Scimè

  5. Istituto di Ematologia, Ospedale Ferrarotto, Catania, Italy

    G Milone

  6. Servizio di Ematologia, Ospedale Maggiore, Torino, Italy

    M Falda

  7. IRCCS, Ospedale Maggiore Policlinico e Università degli Studi, Milano, Italy

    C Vener

  8. Istituto Europeo di Oncologia, Milano, Italy

    D Laszlo

  9. Divisione di Ematologia, Policlinico S. Matteo, Pavia, Italy

    P E Alessandrino

  10. Clinica Ematologica, Policlinico Universitario, Modena, Italy

    F Narni

  11. Istituto di Ematologia, Università Cattolica S. Cuore, Roma, Italy

    S Sica

  12. Clinica di Ematologia, Ospedale Regionale di Torrette, Ancona, Italy

    A Olivieri

  13. Divisione di Ematologia, Policlinico Careggi, Firenze, Italy

    A Bosi

Authors
  1. F Zaja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Bacigalupo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Patriarca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Stanzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M T Van Lint
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Filì
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Scimè
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G Milone
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Falda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C Vener
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D Laszlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P E Alessandrino
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F Narni
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A Olivieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A Sperotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. A Bosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. F Bonifazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. R Fanin
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the GITMO (Gruppo Italiano Trapianto Midollo Osseo)

Corresponding author

Correspondence to F Zaja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zaja, F., Bacigalupo, A., Patriarca, F. et al. Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant 40, 273–277 (2007). https://doi.org/10.1038/sj.bmt.1705725

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705725

Keywords

This article is cited by

Search

Advanced search

Quick links