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Allogeneic stem cell transplantation for patients with relapsed or refractory T-cell lymphoma: efficacy of lymphoma-directed conditioning against advanced disease

Bone Marrow Transplantation (2018) | Download Citation

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Abstract

Salvage chemotherapy induces disease remissions in patients with relapsed or refractory (r/r) T-cell lymphomas, but fails to provide lasting tumor control. We analyzed the outcome after peripheral blood stem and bone marrow transplantation (PBSCT, n = 80; BMT, n = 4) from matched related (MRD, n = 22) or matched and unmatched unrelated donors (MUD and MMD, n = 53 and n = 9, respectively) following conditioning with fludarabine, busulfan, and cyclophosphamide (FBC) for 84 consecutive patients with r/r T-cell malignancies. At start of conditioning LDH was elevated in 50% of cases, and residual tumor (PD, SD, PR) was detectable in 84% of patients. In total, 38% (95% CI 33–44) of the patients were alive and disease-free after a median observation time of 14.5 (range 1.8 to 114) months. Univariate and multivariate analyses identified low ECOG status, as well as occurrence of acute GvHD as favorable factors for outcome. Lymphoma-directed conditioning with fludarabin, busulfan and cyclophosphamid (FBC-12), and allogeneic stem cell transplantation resulted in long-term survival for a proportion of patients with r/r peripheral T-cell lymphoma, including those with PR and SD only after salvage therapy.

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References

  1. 1.

    Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

  2. 2.

    Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group. Blood. 2010;116:3418–25.

  3. 3.

    Zamkoff KW, Matulis MD, Mehta AC, Beaty MW, Hutchison RE, Gentile TC. High-dose therapy and autologous stem cell transplant does not result in long-term disease-free survival in patients with recurrent chemotherapy-sensitive ALK-negative anaplastic large-cell lymphoma. Bone Marrow Transplant. 2004;33:635–8.

  4. 4.

    Blystad AK, Enblad G, Kvaloy S, Berglund A, Delabie J, Holte H, et al. High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas. Bone Marrow Transplant. 2001;27:711–6.

  5. 5.

    D’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30:3093–9.

  6. 6.

    Reimer P, Schertlin T, Rudiger T, Geissinger E, Roth S, Kunzmann V, et al. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5:304–11.

  7. 7.

    Zaja F, Russo D, Silvestri F, Fanin R, Damiani D, Infanti L, et al. Retrospective analysis of 23 cases with peripheral T-cell lymphoma, unspecified: clinical characteristics and outcome. Haematologica. 1997;82:171–7.

  8. 8.

    Gordon BG, Warkentin PI, Weisenburger DD, Vose JM, Sanger WG, Strandjord SE, et al. Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents. Blood. 1992;80:2938–42.

  9. 9.

    Le Gouill S, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol: Off J Am Soc Clin Oncol. 2008;26:2264–71. e-pub ahead of print 2008/04/09

  10. 10.

    Corradini P, Dodero A, Zallio F, Caracciolo D, Casini M, Bregni M, et al. Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin’s lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol. 2004;22:2172–6.

  11. 11.

    Dhedin N, Giraudier S, Gaulard P, Esperou H, Ifrah N, Michallet M, et al. Allogeneic bone marrow transplantation in aggressive non-Hodgkin’s lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Societ Francaise de Greffe de Moelle. Br J Haematol. 1999;107:154–61.

  12. 12.

    Le GS, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol. 2008;26:2264–71.

  13. 13.

    Jacobsen ED, Kim HT, Ho VT, Cutler CS, Koreth J, Fisher DC, et al. A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. Ann Oncol. 2011;22:1608–13.

  14. 14.

    Glass B, Nickelsen M, Dreger P, Claviez A, Hasenkamp J, Wulf G, et al. Reduced-intensity conditioning prior to allogeneic transplantation of hematopoietic stem cells: the need for T cells early after transplantation to induce a graft-versus-lymphoma effect. Bone Marrow Transplant. 2004;34:391–7.

  15. 15.

    Wulf GG, Hasenkamp J, Jung W, Chapuy B, Truemper L, Glass B. Reduced intensity conditioning and allogeneic stem cell transplantation after salvage therapy integrating alemtuzumab for patients with relapsed peripheral T-cell non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2005;36:271–3.

  16. 16.

    Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, et al. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014;15:757–66.

  17. 17.

    Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

  18. 18.

    Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.

  19. 19.

    Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.

  20. 20.

    Mak V, Hamm J, Chhanabhai M, Shenkier T, Klasa R, Sehn LH, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. J Clin Oncol. 2013;31:1970–6.

  21. 21.

    Nickelsen M, Ziepert M, Zeynalova S, Glass B, Metzner B, Leithaeuser M, et al. High-dose CHOP plus etoposide (MegaCHOEP) in T-cell lymphoma: a comparative analysis of patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Ann Oncol. 2009;20:1977–84.

  22. 22.

    Zhang JY, Briski R, Devata S, Kaminski MS, Phillips TJ, Mayer TL, et al. Survival following salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL). Am J Hematol. 2018;93:394–400.

  23. 23.

    Rohlfing S, Dietrich S, Witzens-Harig M, Hegenbart U, Schonland S, Luft T, et al. The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience. Ann Hematol. 2018. https://doi.org/10.1007/s00277-018-3288-7

  24. 24.

    Song KW, Mollee P, Keating A, Crump M. Autologous stem cell transplant for relapsed and refractory peripheral T-cell lymphoma: variable outcome according to pathological subtype. Br J Haematol. 2003;120:978–85.

  25. 25.

    Dodero A, Spina F, Narni F, Patriarca F, Cavattoni I, Benedetti F, et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia. 2012;26:520–6.

  26. 26.

    Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.

  27. 27.

    Foss F. Hematology: relapsed and refractory PTCL--into the therapeutic abyss. Nat Rev Clin Oncol. 2011;8:321–2.

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Author contributions

Conception and design: GW, BG, NS, LT. Collection and assembly of data: GW, BG, GH, CW. Patient care: all coauthors. Data analysis and interpretation: GW, BG, NS, LT. Paper writing: GW, BG, NS, LT, MP. Final approval of paper: all coauthors.

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Author notes

  1. Michael Pfreundschuh is deceased

Affiliations

  1. University Medicine Göttingen, Göttingen, Germany

    • Gerald Wulf
    • , Justin Hasenkamp
    •  & Wolfram Jung
  2. University Hospital Giessen und Marburg, Marburg, Germany

    • Christian Wilhelm
  3. Westpfalz-Klinikum, Kaiserslautern, Germany

    • Gerhard Held
  4. Onkologie Lerchenfeld, Hamburg, Germany

    • Maike Nickelsen
  5. Institut für Medizinische Statistik, Göttingen, Germany

    • Andreas Leha
  6. Universitätsklinikum des Saarlands, Homburg, Germany

    • Michael Pfreundschuh
  7. Universitätsklinikum Münster, Münster, Germany

    • Norbert Schmitz
  8. HELIOS Klinikum Berlin-Buch, Berlin, Germany

    • Bertram Glass

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Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Gerald Wulf.

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DOI

https://doi.org/10.1038/s41409-018-0360-9