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Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party

Bone Marrow Transplantation volume 53, pages 617–624 (2018)Cite this article

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Abstract

Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31–70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3–159), 118 patients relapsed at a median of 8 months post RIST (range 1–117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.

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References

  1. McKay P, Leach M, Jackson R, Cook G, Rule S. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol. 2012;159:405–26.

    Article  CAS  Google Scholar 

  2. Dreyling M, Thieblemont C, Gallamini A, Arcaini L, Campo E, Hermine O, et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24:857–77.

    Article  CAS  Google Scholar 

  3. Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105:2677–84.

    Article  CAS  Google Scholar 

  4. Khouri IF, Romaguera J, Kantarjian H, Palmer JL, Pugh WC, Korbling M, et al. Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol. 1998;16:3803–9.

    Article  CAS  Google Scholar 

  5. Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009;27:6101–8.

    Article  CAS  Google Scholar 

  6. Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood. 2013;121:48–53.

    Article  CAS  Google Scholar 

  7. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008;112:2687–93.

    Article  CAS  Google Scholar 

  8. Gianni AM, Magni M, Martelli M, Di Nicola M, Carlo-Stella C, Pilotti S, et al. Long term remission in mantle cell lymphomafollowing high dose sequential chemotherapy and in vivo rituximab purged stem cell autografting (R-HDS regimen). Blood. 2003;102:749–55.

    Article  CAS  Google Scholar 

  9. Geisler CH, Kolstad A, Laurell A, Jerkman M, Raty R, Niels S, et al. Nordic MCL2 trial update:six year follow up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol. 2012;158:355–62.

    Article  CAS  Google Scholar 

  10. Eskelund CW, Kolstad A, Jerkeman M, Raty R, Laurell A, Eloranta S, et al. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016;175:410–8.

    Article  CAS  Google Scholar 

  11. Cook G, Smith GM, Kirkland K, Lee J, Pearce R, Thomson K, et al. Outcome following reduced-intensity allogeneic stem cell transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2010;16:1419–27.

    Article  Google Scholar 

  12. Fenske TS, Zhang M-J, Carreras J, Ayala E, Burns LJ, Cashen A, et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality. J Clin Oncol. 2014;32:273–81.

    Article  Google Scholar 

  13. Maris MB, Sandmaier BM, Storer BE, Chauncey T, Stuart MJ, Maziarz RT, et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood. 2004;104:3535–42.

    Article  CAS  Google Scholar 

  14. Robinson S, Goldstone AH, Mackinnon S, Carella A, Russell N, Ruiz de Elvira C, et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood. 2002;100:4310–6.

    Article  CAS  Google Scholar 

  15. Tam C, Bassett R, Ledesma C, Korbling M, Alousi A, Hosing C, et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood. 2009;113:4144–52.

    Article  CAS  Google Scholar 

  16. Hamadani M, Saber W, Ahn K, Carreras J, Cairo MS, Fenske T, et al. Allogeneic hematopoietic cell transplantation for chemotherapy-unresponsive mantle cell lymphoma: a cohort analysis from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2013;19:625–31.

    Article  Google Scholar 

  17. Le Gouill S, Kroger N, Dhedin A, Nagler A, Bouaballah, Yakoub-Agha I, et al. Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience. Ann Oncol. 2012;23:2695–703.

    Article  Google Scholar 

  18. Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH, et al. G.Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood. 2003;102:404–6.

    Article  CAS  Google Scholar 

  19. Chakraverty R, Orti G, Roughton M, Shen J, Fielding A, Kottaridis P, et al. Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution. Blood. 2010;116:3080–8.

    Article  CAS  Google Scholar 

  20. Hermine O, Hoster E, Wlewski J, Bosly A, Stilgenbauer S, Thieblemont C, et al. Addition of high dose cytarabine to immunochemotherapy before autologous stem cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomized, open label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388:565–75.

    Article  CAS  Google Scholar 

  21. Peggs K, Cook G, Russell N, Pearce R, Hunter A, Robinson SP et al. Reduced intensity conditioning transplantation (RIC) as part of first line therapy for mantle cell lymphoma: results from the phase II Mini Allo trial (CRUK: C7627/A9080). Bone Marrow Transplant. 2016;51:118.

  22. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507–16.

    Article  CAS  Google Scholar 

  23. Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387:770–8.

    Article  CAS  Google Scholar 

  24. Martin P, Maddocks K, Leonard JP, Ruan J, Goy A, Wagner-Johnston N, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;27:1559–63.

    Article  Google Scholar 

  25. Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2016;126:739–45.

    Article  Google Scholar 

  26. Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, et al. Multicenter open-label phase 2 study of ibrutinib in chronic graft versus host disease (cGVHD) after failure of corticosteroids. Blood. 2016;128:LBA-3.

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Authors and Affiliations

  1. University Hospitals Bristol, Bristol, UK

    Stephen P. Robinson

  2. Lymphoma Working Party EBMT, Paris, France

    Ariane Boumendil & Herve Finel

  3. University College London Hospital, London, UK

    Karl S. Peggs

  4. CHU, Nantes, France

    Patrice Chevallier

  5. Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Jorge Sierra

  6. University of Freiburg, Freiburg im Breisgau, Germany

    Jürgen Finke

  7. Cliniques Universitaires St. Luc, Brussels, Belgium

    Xavier Poiré

  8. Hôpital La Miletrie, Poitiers, France

    Natacha Maillard

  9. CHU Bordeaux, Bordeaux, France

    Noël Milpied

  10. Hôpital Huriez, Lille, France

    Ibrahim Yakoub-Agha

  11. St. George’s Hospital, London, UK

    Mickey Koh

  12. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  13. Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel

    Arnon Nagler

  14. Medical Park Hospitals, Antalya, Turkey

    Yener Koc

  15. University of Heidelberg, Heidelberg, Germany

    Sascha Dietrich & Peter Dreger

  16. St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK

    Silvia Montoto

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  1. Stephen P. Robinson
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Correspondence to Stephen P. Robinson.

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Robinson, S., Boumendil, A., Finel, H. et al. Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party. Bone Marrow Transplant 53, 617–624 (2018). https://doi.org/10.1038/s41409-017-0067-3

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  • DOI: https://doi.org/10.1038/s41409-017-0067-3

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