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Allografting

Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation

Bone Marrow Transplantation volume 36, pages 91–97 (2005)Cite this article

Summary:

Relapse is a major problem after allogeneic transplantation in children with acute B-lineage lymphoblastic leukemias (ALL) and lymphomas and additional therapeutic strategies are needed to increase graft versus leukemia effects without inducing graft versus host disease (GvHD). Several studies have shown the efficacy of a humanized CD20 antibody (rituximab) for treatment of CD20+ malignancies together with conventional chemotherapy but less is known about its post transplant usefulness. We studied the ability of rituximab to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with effector cells and complement from patients who were transplanted with T-cell-depleted grafts from unrelated or mismatched related donors. Highest lytic activity (ADCC) was observed against leukemia-derived MHH4 cells and Burkitt's lymphoma-derived Raji cells in the first months after transplantation, corresponding to the high percentage of regenerating CD56+CD16+ cells. Moreover, primary cryopreserved ALL-blasts from a pediatric patient were also efficiently lysed. Increased lysis was obtained after stimulation with interleukin-2. Combination of ADCC and CDC had additive effects. These findings encourage clinical trials on the use of rituximab for improving minimal residual disease control and relapse prevention after allogeneic high-risk transplantation in the small group of pediatric patients with CD20+ leukemias/lymphomas.

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References

  1. Kernan NA, Bartsch G, Ash RC et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 1993; 328: 593–602.

    Article  CAS  Google Scholar 

  2. Ortin M, Raj R, Kinning E et al. Partially matched related donor peripheral blood progenitor cell transplantation in paediatric patients adding fludarabine and anti-lymphocyte gamma-globulin. Bone Marrow Transplant 2002; 30: 359–366.

    Article  CAS  Google Scholar 

  3. Lang P, Handgretinger R, Niethammer D et al. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood 2003; 101: 1630–1636.

    Article  CAS  Google Scholar 

  4. Bunin N, Carston M, Wall D et al. Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood 2002; 99: 3151–3157.

    Article  CAS  Google Scholar 

  5. Rocha V, Cornish J, Sievers EL et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  Google Scholar 

  6. Coiffier B, Haioun C, Ketterer N et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood 1998; 92: 1927–1932.

    CAS  Google Scholar 

  7. Sacchi S, Federico M, Dastoli G et al. Treatment of B-cell non-Hodgkin's lymphoma with anti CD 20 monoclonal antibody Rituximab. Crit Rev Oncol Hematol 2001; 37: 13–25.

    Article  CAS  Google Scholar 

  8. Huhn D, von Schilling C, Wilhelm M et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood 2001; 98: 1326–1331.

    Article  CAS  Google Scholar 

  9. Cartron G, Dacheux L, Salles G 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  Google Scholar 

  10. 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  Google Scholar 

  11. Golay J, Gramigna R, Facchinetti V et al. 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  Google Scholar 

  12. Manches O, Lui G, Chaperot L et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 2003; 101: 949–954.

    Article  CAS  Google Scholar 

  13. Shimoni A, Hardan I, Avigdor A 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  Google Scholar 

  14. Lang P, Pfeiffer M, Handgretinger R et al. Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children. Bone Marrow Transplant 2002; 29: 497–502.

    Article  CAS  Google Scholar 

  15. Brugger W . Clearing minimal residual disease with rituximab consolidation therapy. Semin Oncol 2004; 31 (1 Suppl. 2): 33–37.

    Article  CAS  Google Scholar 

  16. Ruggeri L, Capanni M, Urbani E et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    Article  CAS  Google Scholar 

  17. Golay J, Manganini M, Facchinetti V et al. Rituximab-mediated antibody-dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by interleukin-2. Haematologica 2003; 88: 1002–1012.

    CAS  PubMed  Google Scholar 

  18. Friedberg JW, Neuberg D, Gribben JG et al. Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma. Br J Haematol 2002; 117: 828–834.

    Article  CAS  Google Scholar 

  19. Lang P, Greil J, Schumm M . Boosts with highly purified stem cells following allogeneic transplantation from alternative donors. Bone Marrow Transplant 2003; 31: 238.

    Google Scholar 

  20. Hillmen P . Advancing therapy for chronic lymphocytic leukemia – the role of rituximab. Semin Oncol 2004; 31 (1 Suppl. 2): 22–26.

    Article  CAS  Google Scholar 

  21. Anderson KC, Bates MP, Slaughenhoupt BL et al. Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 1984; 63: 1424–1433.

    CAS  PubMed  Google Scholar 

  22. Lang P, Barbin K, Feuchtinger T et al. Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts. Blood 2004; 103: 3982–3985.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A Babarin-Dorner for excellent technical assistance, Karin Schilbach, PhD and Barbara Lang, MD, for helping prepare the manuscript. This work was supported by grants from the German José Carreras Leukemia Foundation, the Deutsche Forschungsgemeinschaft (SFB 510) and from the Reinhold Beitlich Stiftung, Tuebingen, Germany.

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Authors and Affiliations

  1. Department of Pediatric Oncology, University Children's Hospital, University of Tuebingen, Tuebingen, Germany

    M Pfeiffer, S Stanojevic, T Feuchtinger, J Greil, D Martin, D Niethammer & P Lang

  2. Stem Cell Transplantation Unit, St Jude Children's Research Hospital, Memphis, TN, USA

    R Handgretinger

  3. Department of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany

    K Barbin

  4. Department of Immunology, Institute for Cell Biology, University of Tuebingen, Tuebingen, Germany

    G Jung

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  1. M Pfeiffer
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Correspondence to P Lang.

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Pfeiffer, M., Stanojevic, S., Feuchtinger, T. et al. Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation. Bone Marrow Transplant 36, 91–97 (2005). https://doi.org/10.1038/sj.bmt.1705014

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