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Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials

Leukemia volume 30, pages 1428–1430 (2016)Cite this article

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In patients with mantle cell lymphoma (MCL) up to 65 years, recommended first-line treatment consists of immuno-chemotherapy including high-dose cytarabine (HA), followed by autologous stem cell transplantation (ASCT) in complete (CR) or partial remission (PR).1 However, it remains unclear whether total body irradiation (TBI) should be part of conditioning before ASCT.1 A large registry study by the European Society for Blood and Marrow Transplantation (EBMT) including 418 MCL patients reported a significantly reduced relapse incidence after TBI in comparison to a non-TBI conditioning (mostly carmustine, etoposide, cytarabine, and melphalan, BEAM), but only for patients transplanted in first PR.2 In contrast, a single-center evaluation of 73 MCL patients who underwent ASCT did not find a significant PFS difference according to the use of TBI vs BEAM.3 A recently published consensus project by EBMT/European MCL Network involving twelve expert clinicians showed that, while consensus was achieved on ASCT as standard first-line consolidation therapy, no consensus was reached on the role of TBI.4 Three recently completed prospective studies including untreated MCL patients up to 65 years investigated the efficacy of HA-containing immuno-chemotherapy followed by ASCT: Nordic MCL2,5, 6 HOVON-45(ref. 7) and European MCL Younger.8, 9 We combined the individual patient data from these studies to compare the long-term clinical outcome of MCL patients transplanted without TBI (Nordic MCL2 and HOVON-45) vs with TBI (MCL Younger, experimental HA-containing arm).

The trials included adult patients up to 65 years with untreated stage II–IV MCL. Induction in Nordic MCL2 consisted of six alternating cycles of cyclophosphamide, vincristine, doxorubicin and prednisone (Maxi-CHOP) or HA combined with four or six cycles rituximab. In HOVON-45 three courses R-CHOP were followed by one cycle R-HA. The experimental group of MCL Younger received six alternating cycles R-CHOP or rituximab, dexamethasone, HA, and cisplatinum (R-DHAP). Conditioning before ASCT consisted of BEAM or carmustin, etoposide, cytarabine, cyclophosphamide (BEAC) in Nordic MCL2, and BEAM in HOVON-45, whereas a TBI-containing regimen (TBI: 10 Gray fractionated over 3 days, HA, melphalan) was applied in the experimental arm of MCL Younger. The total cumulative HA dose was 36 g/m2 (24 if ⩾60 years) in Nordic MCL2, 16.8 g/m2 in HOVON-45 and 18 g/m2 in MCL Younger. End of induction staging was performed after cycle 5 in Nordic MCL2, after HA in HOVON-45, and after cycle 6 in MCL Younger, using the same criteria.10

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Author notes

  1. M Dreyling and O Hermine: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine III, University Hospital Munich, Munich, Germany

    E Hoster, M Unterhalt & M Dreyling

  2. Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich, Munich, Germany

    E Hoster

  3. Hematology Department, Rigshospitalet, Copenhagen, Denmark

    C H Geisler

  4. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    J Doorduijn & M van't Veer

  5. HOVON Data Center, Erasmus MC Cancer Institute - Clinical Trial Center, Rotterdam, The Netherlands

    B van der Holt

  6. Department of Lymphoid Malignancies, The Maria Skłodowska-Curie Memorial Institute and Oncology Center, Warsaw, Poland

    J Walewski & M Szymczyk

  7. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    J Bloehdorn

  8. Institut Gustave Roussy, Villejuif, France

    V Ribrag

  9. Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite, France

    G Salles

  10. Department I of Internal Medicine, University of Cologne, Cologne, Germany

    M Hallek

  11. Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    C Pott

  12. Oncology Department, The Norwegian Radium Hospital, Oslo, Norway

    A Kolstad

  13. Department of Oncology, Uppsala University Hospital, Uppsala, Sweden

    A Laurell

  14. Department of Hematology, Helsinki University Central Hospital, Helsinki, Finland

    R Räty

  15. Department of Oncology, Skane University Hospital, Lund, Sweden

    M Jerkeman

  16. Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    J C Kluin-Nelemans

  17. Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, Kiel, Germany

    W Klapper

  18. Department of Hematology, Hôpital Necker, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France

    O Hermine

  19. INSERM U1163 and CNRS 8254, Imagine Institute, Université Sorbonne Paris Cité, Paris, France

    O Hermine

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  1. E Hoster
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  2. C H Geisler
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  19. M Unterhalt
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for the European Mantle Cell Lymphoma Network

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Correspondence to E Hoster.

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Competing interests

WK has received grants and travel reimbursement from Roche, Celgene, Janssen, Novartis and Takeda/Millenium not related to the project and paid to the institution. All other authors declare no competing financial interests.

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Author contributions

EH, CHG, JD, MU, MD and OH designed and performed research, CHG, JD, BvdH, JW, JB, VR, GS, MH, CP, MS, AK, AL, RR, MJ, MvV, JCK-N, WK, MU, MD and OH acquired data, EH performed statistical analysis and drafted the manuscript, EH, CHG, MD and OH interpreted data, all authors revised the manuscript and approved the final version of the manuscript.

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Hoster, E., Geisler, C., Doorduijn, J. et al. Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials. Leukemia 30, 1428–1430 (2016). https://doi.org/10.1038/leu.2015.322

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