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.

  • Correspondence
  • Published:

Comparison of MEAM, MCEC and LEED high-dose chemotherapy followed by autologous stem cell transplantation in relapsed/refractory diffuse large B-cell lymphoma: data from the Japan Society for Hematopoietic and Cellular Therapy Registry

Bone Marrow Transplantation volume 59, pages 125–127 (2024)Cite this article

Subjects

The high-dose chemotherapy (HDC) regimen frequently used for autologous stem cell transplantation (ASCT) in lymphoma is the BEAM (carmustine [BCNU], etoposide, cytarabine, melphalan) regimen in Western countries but not in Japan due to the unavailability of carmustine. The common HDC regimens in Japan are an alternative form of BEAM (MEAM; ranimustine [300 mg/m² on day −6], etoposide [200 mg/m² on day −5 to −2], cytarabine [200 mg/m² twice daily on days −5 to −2], and melphalan [140 mg/m² on day −1]) [1], MCEC (ranimustine [MCNU] 200 mg/m2 on days −8, −3, carboplatin [300 mg/m2 on days −7 to −4], etoposide [500 mg/m2 on days −6 to −4] and cyclophosphamide [50 mg/kg on days −3, −2]) [2] and LEED (cyclophosphamide [50 mg/kg on days −4, −3], etoposide [250 mg/m² twice daily on days −4 to −2], melphalan [130 mg/m² on day −1], and dexamethasone) [3]; however, data comparing these regimens are scarce [4]. In patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL), salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell support/transplantation (HDC-ASCT) has been a standard of care which is chemotherapy-sensitive still in the chimeric antigen receptor T (CAR-T) era, except for relapsed DLBCL patients with early progression within a year [5]. Here, we assessed the outcomes of patients with relapsed or refractory (r/r) DLBCL undergoing ASCT with the three common HDC regimens in the Japan Society for Hematopoietic and Cellular Therapy (JSTCT) Registry [6].

Patients with r/r DLBCL who underwent their first HDC-ASCT between 2004 and 2016 were included. The patient selection consort diagram is shown in Supplementary Fig. S1. Overall survival (OS) was defined as the time from transplantation to death or the latest follow-up. Progression-free survival (PFS) was defined as the time from transplantation to relapse/progression or death from any cause or latest follow-up. Non-relapse mortality (NRM) was defined as death without evidence of relapse or progression. Differences in the distribution of clinical characteristics between groups were analyzed with Fisher’s exact test or the Mann–Whitney U test. Survival curves were calculated using the Kaplan–Meier product limit estimate [7], groups were compared using the log-rank test, and risk factor analysis was performed using a Cox regression model [8]. The cumulative incidence of relapse and NRM was determined using the Gray test. Statistical analyses were performed with Stata version 15 (Stata Corp, College Station, TX).

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

Fig. 1: Survival analysis by the three common HDC regimens.

References

  1. Sugimoto M, Ito S, Mashima K, Umino K, Minakata D, Nakano H, et al. Retrospective evaluation of the MEAM regimen as a conditioning regimen before autologous peripheral blood stem cell transplantation for lymphoma in two centers with different dosing schedules of melphalan. Ann Hematol. 2016;95:1513–9.

    Article  CAS  PubMed  Google Scholar 

  2. Asakura Y, Tanosaki R, Kim S-W, Azuma T, Kurosawa S, Yakushijin K, et al. Cytoreductive regimen containing ranimustine (MCNU),carboplatin, etoposide and cyclophosphamide (MCEC) before autologous peripheral blood stem cell transplantation for relapsed or refractory lymphoma. Blood. 2008;112:4448.

    Article  Google Scholar 

  3. Han LN, Zhou J, Hirose T, Imai Y, Ishiguro T, Chou T. Feasibility and efficacy of high-dose melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) chemotherapy with or without rituximab followed by autologous stem cell transplantation for aggressive and relapsed non-Hodgkin’s lymphoma. Int J Hematol. 2006;84:174–81.

    Article  CAS  PubMed  Google Scholar 

  4. Kondo E. Autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma. J Clin Exp Hematop. 2016;56:100–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Melchardt T, Egle A, Greil R. How I treat diffuse large B-cell lymphoma. ESMO Open. 2023;8:100750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Atsuta Y. Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol. 2016;103:3–10.

    Article  PubMed  Google Scholar 

  7. Dinse GE, Lagakos SW. Nonparametric estimation of lifetime and disease onset distributions from incomplete observations. Biometrics. 1982;38:921–32.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang MJ. Cox proportional hazards regression models for survival data in cancer research. Cancer Treat Res. 2002;113:59–70.

    Article  PubMed  Google Scholar 

  9. Olivieri J, Mosna F, Pelosini M, Fama A, Rattotti S, Giannoccaro M, et al. A comparison of the conditioning regimens BEAM and FEAM for autologous hematopoietic stem cell transplantation in lymphoma: an observational study on 1038 patients from Fondazione Italiana Linfomi. Biol Blood Marrow Transpl. 2018;24:1814–22.

    Article  Google Scholar 

  10. Chen YBin, Lane AA, Logan BR, Zhu X, Akpek G, Aljurf MD, et al. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2015;21:1046–53.

    Article  Google Scholar 

  11. Robinson SP, Boumendil A, Finel H, Dreger P, Sureda A, Hermine O, et al. High-dose therapy with BEAC conditioning compared to BEAM conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: no differences in toxicity or outcome. A matched-control study of the EBMT-Lymphoma Working Party. Bone Marrow Transplant. 2018;53:1553–9.

    Article  CAS  PubMed  Google Scholar 

  12. Hueso T, Gastinne T, Garciaz S, Tchernonog E, Delette C, Casasnovas RO, et al. Bendamustine-EAM versus BEAM regimen in patients with mantle cell lymphoma undergoing autologous stem cell transplantation in the frontline setting: a multicenter retrospective study from Lymphoma Study Association (LYSA) centers. Bone Marrow Transplant. 2020;55:1076–84.

    Article  CAS  PubMed  Google Scholar 

  13. Hahn L, Lim H, Dusyk T, Sabry W, Elemary M, Stakiw J, et al. BeEAM conditioning regimen is a safe, efficacious and economical alternative to BEAM chemotherapy. Sci Rep. 2021;11:14071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, et al. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011;118:3419–25.

    Article  CAS  PubMed  Google Scholar 

  15. Marchesi F, Capria S, Giannarelli D, Trisolini SM, Ansuinelli M, Caputo MD, et al. BEAM vs FEAM high-dose chemotherapy: retrospective study in lymphoma patients undergoing autologous stem cell transplant. Bone Marrow Transplant. 2018;53:1051–4.

    Article  CAS  PubMed  Google Scholar 

  16. Sellner L, Boumendil A, Finel H, Choquet S, De Rosa G, Falzetti F, et al. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT. Bone Marrow Transplant. 2016;51:212–8.

    Article  CAS  PubMed  Google Scholar 

  17. Jo JC, Kim JS, Lee JH, Lee JH, Lim SN, Lee SM, et al. Busulfan, etoposide, cytarabine, and melphalan (BuEAM) as a conditioning regimen for autologous stem cell transplantation in patients with non-Hodgkin lymphoma (NHL). Bone Marrow Transpl. 2020;55:1466–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all the physicians and data managers at the hospitals and centers who contributed valuable data on transplantation to the Japan Society for Hematopoietic and Cellular Therapy Registry.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Department of Hematology, Kawasaki Medical School, Kurashiki, Japan

    Risa Koresawa-Shimizu & Eisei Kondo

  2. Department of Oncology/Hematology, Shimane University Hospital, Izumo, Japan

    Ritsuro Suzuki

  3. Department of Hematology, Kitakyushu City Hospital Organization, Kitakyushu Municipal Medical Center, Kokura, Japan

    Yasufumi Uehara

  4. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Nobuhiro Hiramoto

  5. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Masashi Sawa

  6. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  7. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Keisuke Kataoka

  8. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Yoshinobu Kanda

  9. Division of Hematology and Oncology, Iwate Medical University, Iwate, Japan

    Tatsuo Oyake

  10. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Yasushi Kubota

  11. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations TORANOMON HOSPITAL, Tokyo, Japan

    Naoyuki Uchida

  12. Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

  13. Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan

    Hikaru Kobayashi

  14. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Junji Tanaka

  15. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  16. Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

Authors
  1. Risa Koresawa-Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ritsuro Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasufumi Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nobuhiro Hiramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masashi Sawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Keisuke Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshinobu Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tatsuo Oyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yasushi Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Naoyuki Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shingo Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hikaru Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Junji Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yoshiko Atsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Eisei Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RKS, EK and RS participated actively in the study conception and design; YU, NH, MS, TF, KK, YK, TO, YK, NK, SY and HK provided patient data; TF, JT, and YA contributed to the administrative support of the study; RKS and EK conducted the data analysis and interpretation and wrote the first draft of the manuscript; RKS and EK critically revised the manuscript; and all authors approved the final version.

Corresponding author

Correspondence to Eisei Kondo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koresawa-Shimizu, R., Suzuki, R., Uehara, Y. et al. Comparison of MEAM, MCEC and LEED high-dose chemotherapy followed by autologous stem cell transplantation in relapsed/refractory diffuse large B-cell lymphoma: data from the Japan Society for Hematopoietic and Cellular Therapy Registry. Bone Marrow Transplant 59, 125–127 (2024). https://doi.org/10.1038/s41409-023-02118-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-023-02118-w

Search

Advanced search

Quick links