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:

Allografting

Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia

Bone Marrow Transplantation volume 38, pages 203–209 (2006)Cite this article

Abstract

We explored the safety and efficacy of rituximab administered in combination with the standard transplant conditioning regimen of cyclophosphamide (Cy) 120 mg/kg and total body irradiation (TBI) 12 Gy for adult patients with acute lymphoblastic leukemia (ALL). Patients were eligible if their disease expressed CD20. Rituximab was administered at 375 mg/m2 weekly for four doses beginning on day −7 of the conditioning regimen. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-five patients undergoing matched sibling (n=23) or unrelated donor (n=12) transplantation were studied, with a median age of 30 years (range 15–55 years). At 2 years, progression-free survival, treatment-related mortality, and overall survival were 30, 24, and 47%, respectively. There was no delay in engraftment or increased incidence of infection. The cumulative incidence of grade II–IV acute GVHD was 17%, and limited and extensive chronic GVHD was 43% at 2 years. The addition of rituximab to the standard Cy/TBI transplant conditioning regimen in ALL was safe and well tolerated, and there was a suggestion of decreased incidence of acute GVHD when compared to historically reported GVHD rates for this group of patients.

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
Figure 3

Similar content being viewed by others

References

  1. Bortin MM, Horowitz MM, Gale RP, Barrett AJ, Champlin RE, Dicke KA et al. Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s. JAMA 1992; 268: 607–612.

    Article  CAS  PubMed  Google Scholar 

  2. Chao NJ, Forman SJ, Schmidt GM, Snyder DS, Amylon MD, Konrad PN et al. Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission. Blood 1991; 78: 1923–1927.

    CAS  PubMed  Google Scholar 

  3. Forman SJ, Schmidt GM, Nademanee AP, Amylon MD, Chao NJ, Fahey JL et al. Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. J Clin Oncol 1991; 9: 1570–1574.

    Article  CAS  PubMed  Google Scholar 

  4. Biggs JC, Horowitz MM, Gale RP, Ash RC, Atkinson K, Helbig W et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 1992; 80: 1090–1093.

    CAS  PubMed  Google Scholar 

  5. Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C et al. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation. A follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am 2000; 14: 1353–1366.

    Article  CAS  PubMed  Google Scholar 

  6. Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J et al. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol 1994; 12: 2580–2587.

    Article  CAS  PubMed  Google Scholar 

  7. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.

    Article  CAS  PubMed  Google Scholar 

  8. Kiehl MG, Kraut L, Schwerdtfeger R, Hertenstein B, Remberger M, Kroeger N et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission. J Clin Oncol 2004; 22: 2816–2825.

    Article  PubMed  Google Scholar 

  9. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994; 83: 435–445.

    CAS  PubMed  Google Scholar 

  10. Gokbuget N, Hoelzer D . Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. Ann Hematol 2004; 83: 201–205.

    Article  PubMed  Google Scholar 

  11. Thomas D, Giles F, O'Brien S, Faderl S, Garcia-Manero G, Beran M et al. Update of the modified hyper-CVAD regimen in newly diagnosed adult acute lymphocytic leukemia (ALL). American Society of Hematology: San Diego, CA, USA, 2003. p. 3274a.

  12. Thomas D, Faderl S, O'Brien S, Beran M, Koller C, Garcia-Manero G et al. Outcome with the hyper-CVAD and rituximab regimen in Burkitt (BL) and Burkitt-like (BLL) leukemia/lymphoma. American Society of Hematology: San Diego, California, 2004. p. 3297a.

  13. Fuchs EJ, Whartenby KA . Hematopoietic stem cell transplant as a platform for tumor immunotherapy. Curr Opin Mol Ther 2004; 6: 48–53.

    CAS  PubMed  Google Scholar 

  14. 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  PubMed  Google Scholar 

  15. 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; 104: 2603–2606.

    Article  CAS  PubMed  Google Scholar 

  16. Cutler C, Miklos D, Lee SJ, Woo SB, Treister N, Bien-fang D et al. Rituxan for steroid refractory chronic GVHD. American Society of Blood and Marrow Transplantation, Colorado, 2005. p 29a.

    Article  Google Scholar 

  17. Ratanatharathorn V, Bociek RG, Pavlovic S, Lynch JC, Ferrara JCM, Uberti JP . Prior therapy with anti-CD20 chimeric antibody (Rituximab) may decrease risk of acute graft versus host disease (GVHD) in patients with non-Hodgkin's lymphoma receiving allogeneic stem cell transplantation. American Society of Hematology: Florida, 2001, p 391a.

  18. Vriesendorp HM, Chu H, Ochran TG, Besa PC, Champlin RE . Radiobiology of total body radiation. Bone Marrow Transplant 1994; 14 (Suppl 4): S4–S8.

    PubMed  Google Scholar 

  19. Gopal R, Ha CS, Tucker SL, Khouri IF, Giralt SA, Gajewski JL et al. Comparison of two total body irradiation fractionation regimens with respect to acute and late pulmonary toxicity. Cancer 2001; 92: 1949–1958.

    Article  CAS  PubMed  Google Scholar 

  20. 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 

  21. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.

    CAS  PubMed  Google Scholar 

  22. Kaplan E . Nonparametric estimation for incomplete observations. Journal of American Statistical Association 1958; 53: 457–481.

    Article  Google Scholar 

  23. Hoelzer D, Thiel E, Loffler H, Buchner T, Ganser A, Heil G et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 1988; 71: 123–131.

    CAS  PubMed  Google Scholar 

  24. Cornelissen JJ, Carston M, Kollman C, King R, Dekker AW, Lowenberg B et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001; 97: 1572–1577.

    Article  CAS  PubMed  Google Scholar 

  25. Shlomchik WD, Couzens MS, Tang CB, McNiff J, Robert ME, Liu J et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999; 285: 412–415.

    Article  CAS  PubMed  Google Scholar 

  26. Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D et al. Donor APCs are required for maximal GVHD but not for GVL. Nat Med 2004; 10: 987–992.

    Article  CAS  PubMed  Google Scholar 

  27. Anderson BE, McNiff JM, Jain D, Blazar BR, Shlomchik WD, Shlomchik MJ . Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease: requirements depend on target organ. Blood 2005; 105: 2227–2234.

    Article  CAS  PubMed  Google Scholar 

  28. Kurt-Jones EA, Liano D, HayGlass KA, Benacerraf B, Sy MS, Abbas AK . The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice. J Immunol 1988; 140: 3773–3778.

    CAS  PubMed  Google Scholar 

  29. Batista FD, Iber D, Neuberger MS . B cells acquire antigen from target cells after synapse formation. Nature 2001; 411: 489–494.

    Article  CAS  PubMed  Google Scholar 

  30. Schultz KR, Paquet J, Bader S, HayGlass KT . Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease. Bone Marrow Transplant 1995; 16: 289–295.

    CAS  PubMed  Google Scholar 

  31. Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 2001; 98: 3595–3599.

    Article  CAS  PubMed  Google Scholar 

  32. Shimoni A, Hardan I, Avigdor A, Yeshurun M, Raanani P, Ben-Bassat I et al. Rituximab reduces relapse risk after allogeneic and autologous stem cell transplantation in patients with high-risk aggressive non-Hodgkin's lymphoma. Br J Haematol 2003; 122: 457–464.

    Article  CAS  PubMed  Google Scholar 

  33. Appelbaum FR . Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). Leukemia 1997; 11 (Suppl 4): S15–S17.

    PubMed  Google Scholar 

  34. Clynes RA, Towers TL, Presta LG, Ravetch JV . Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000; 6: 443–446.

    Article  CAS  PubMed  Google Scholar 

  35. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 2002; 99: 754–758.

    Article  CAS  PubMed  Google Scholar 

  36. Golay J, Gramigna R, Facchinetti V, Capello D, Gaidano G, Introna M . Acquired immunodeficiency syndrome-associated lymphomas are efficiently lysed through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by rituximab. Br J Haematol 2002; 119: 923–929.

    Article  CAS  PubMed  Google Scholar 

  37. Manches O, Lui G, Chaperot L, Gressin R, Molens JP, Jacob MC et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 2003; 101: 949–954.

    Article  CAS  PubMed  Google Scholar 

  38. Pfeiffer M, Stanojevic S, Feuchtinger T, Greil J, Handgretinger R, Barbin K et al. Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation. Bone Marrow Transplant 2005; 36: 91–97.

    Article  CAS  PubMed  Google Scholar 

  39. Khouri IF, Lee MS, Saliba RM, Andersson B, Anderlini P, Couriel D et al. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol 2004; 32: 28–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    P Kebriaei, R M Saliba, C Ma, C Ippoliti, D R Couriel, M de Lima, S Giralt, M H Qazilbash, J L Gajewski, C S Ha, R E Champlin & I F Khouri

Authors
  1. P Kebriaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R M Saliba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Ippoliti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D R Couriel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Giralt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M H Qazilbash
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J L Gajewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C S Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R E Champlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. I F Khouri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Kebriaei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kebriaei, P., Saliba, R., Ma, C. et al. Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia. Bone Marrow Transplant 38, 203–209 (2006). https://doi.org/10.1038/sj.bmt.1705425

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705425

Keywords

This article is cited by

Search

Advanced search

Quick links