Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

1st Faculty of Medicine Charles University Praha Czech Republic

Charité Universitätsmedizin Berlin Freie Universität Berlin and Humboldt Universität Berlin Department of Hematology Oncology and Tumor Immunology Campus Virchow Clinic Berlin Germany

CHU Institut Universitaire du Cancer Toulouse Oncopole 1 U C T O Toulouse France

Department of Hemato Oncology Hôpital Saint Louis APHP Paris France

Department of Hematology Amsterdam University Medical Center Free University Amsterdam the Netherlands

Department of Hematology and Oncology Saarland University Medical School Homburg Germany

Department of Hematology and Oncology University Hospital Muenster Muenster Germany

Department of Hematology AP HP Sorbonne Université Pitié Salpêtrière Hospital Paris France

Department of Hematology CHU Dijon Dijon France

Department of Hematology CHU Nantes Nantes France

Department of Hematology Erasmus MC Cancer Institute Rotterdam Netherlands

Department of Hematology Gustave Roussy Cancer Campus Villejuif France

Department of Hematology Institut Català d'Oncologia Hospitalet IDIBELL Universitat de Barcelona Barcelona Spain

Department of Hematology Oncology and Stem Cell Transplantation University of Freiburg Medical Center Freiburg Germany

Department of Hematology Oncology Tumor Immunology and Palliative Care Helios Klinikum Berlin Buch Berlin Germany

Department of Hematology University College London Hospitals London United Kingdom

Department of Internal Medicine 5 Hematology and Oncology University of Erlangen Nuremberg Erlangen Germany

Department of Medicine 5 University of Heidelberg Heidelberg Germany

Department of Translational and Precision Medicine Policlinico Umberto 1 Hospital Sapienza University of Rome Rome Italy

Division of Hematology Sheba Medical Center Tel Hashomer Israel

European Society for Blood and Marrow Transplantation Paris France

HCA Healthcare Macmillan Cancer Centre London United Kingdom

Hospices Civils de Lyon Hôpital Lyon Sud Service d'Hématologie Pierre Bénite France

Service d'Hématologie Clinique et Thérapie Cellulaire CHU Bordeaux F 33000 Bordeaux France

St Bartholomew's Hospital Barts Health NHS Trust London United Kingdom

Transplantation and Cellular Immunotherapy Program Department of Hematology Instititut Paoli Calmettes MSC Lab Aix Marseille University Marseille France

Zobrazit více v PubMed

Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N. Engl J Med. 1995;333:1540–5. doi: 10.1056/NEJM199512073332305. PubMed DOI

Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum LG, Momin F, et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin’s lymphoma. Blood. 1994;84:1050–5. doi: 10.1182/blood.V84.4.1050.1050. PubMed DOI

Bosly A, Coiffier B, Gisselbrecht C, Tilly H, Auzanneau G, Andrien F, et al. Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen. J Clin Oncol. 1992;10:1615–23. doi: 10.1200/JCO.1992.10.10.1615. PubMed DOI

Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC, et al. High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 1993;11:1846–51. doi: 10.1200/JCO.1993.11.10.1846. PubMed DOI

Chopra R, Goldstone AH, Pearce R, Philip T, Petersen F, Appelbaum F, et al. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin’s lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data. J Clin Oncol. 1992;10:1690–5. doi: 10.1200/JCO.1992.10.11.1690. PubMed DOI

Reece DE, Barnett MJ, Connors JM, Fairey RN, Fay JW, Greer JP, et al. Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin’s disease. J Clin Oncol. 1991;9:1871–9. doi: 10.1200/JCO.1991.9.10.1871. PubMed DOI

Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32:3490–6. doi: 10.1200/JCO.2013.53.9593. PubMed DOI

Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28:4184–90. doi: 10.1200/JCO.2010.28.1618. PubMed DOI PMC

Oliansky DM, Czuczman M, Fisher RI, Irwin FD, Lazarus HM, Omel J, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of diffuse large B cell lymphoma: update of the 2001 evidence-based review. Biol Blood Marrow Transpl. 2011;17:20–47.e30. doi: 10.1016/j.bbmt.2010.07.008. PubMed DOI

Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N. Engl J Med. 1979;300:1068–73. doi: 10.1056/NEJM197905103001902. PubMed DOI

Bishop MR, Dean RM, Steinberg SM, Odom J, Pavletic SZ, Chow C, et al. Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation. Ann Oncol. 2008;19:1935–40. doi: 10.1093/annonc/mdn404. PubMed DOI PMC

Thomson KJ, Morris EC, Bloor A, Cook G, Milligan D, Parker A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27:426–32. doi: 10.1200/JCO.2008.17.3328. PubMed DOI

van Kampen RJ, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant JP, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol. 2011;29:1342–8. doi: 10.1200/JCO.2010.30.2596. PubMed DOI

Urbano-Ispizua A, Pavletic SZ, Flowers ME, Klein JP, Zhang MJ, Carreras J, et al. The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen. Biol Blood Marrow Transpl. 2015;21:1746–53. doi: 10.1016/j.bbmt.2015.05.010. PubMed DOI PMC

Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76:2462–5. doi: 10.1182/blood.V76.12.2462.2462. PubMed DOI

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. doi: 10.1016/S1470-2045(14)70161-5. PubMed DOI

Rezvani AR, Norasetthada L, Gooley T, Sorror M, Bouvier ME, Sahebi F, et al. Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience. Br J Haematol. 2008;143:395–403. doi: 10.1111/j.1365-2141.2008.07365.x. PubMed DOI PMC

Khouri IF, Keating M, Korbling M, Przepiorka D, Anderlini P, O’Brien S, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16:2817–24. doi: 10.1200/JCO.1998.16.8.2817. PubMed DOI

McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–400. doi: 10.1182/blood.V97.11.3390. PubMed DOI

Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996;347:353–7. doi: 10.1016/S0140-6736(96)90536-X. PubMed DOI

Beyer J, Schwella N, Zingsem J, Strohscheer I, Schwaner I, Oettle H, et al. Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison. J Clin Oncol. 1995;13:1328–35. doi: 10.1200/JCO.1995.13.6.1328. PubMed DOI

Schmitz N, Dreger P, Suttorp M, Rohwedder EB, Haferlach T, Loffler H, et al. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor) Blood. 1995;85:1666–72. doi: 10.1182/blood.V85.6.1666.bloodjournal8561666. PubMed DOI

Stem Cell Trialists’ Collaborative G. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005;23:5074–87. doi: 10.1200/JCO.2005.09.020. PubMed DOI PMC

Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N. Engl J Med. 2022;386:640–54. doi: 10.1056/NEJMoa2116133. PubMed DOI

Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N. Engl J Med. 2017;377:2531–44. doi: 10.1056/NEJMoa1707447. PubMed DOI PMC

Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N. Engl J Med. 2022;386:629–39. doi: 10.1056/NEJMoa2116596. PubMed DOI

Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl J Med. 2019;380:45–56. doi: 10.1056/NEJMoa1804980. PubMed DOI

Cwynarski K, van Biezen A, de Wreede L, Stilgenbauer S, Bunjes D, Metzner B, et al. Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter’s syndrome): A retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012;30:2211–17. doi: 10.1200/JCO.2011.37.4108. PubMed DOI

Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transpl. 2009;15:367–9. doi: 10.1016/j.bbmt.2008.12.497. PubMed DOI PMC

Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401.e1. doi: 10.1016/j.bbmt.2014.12.001. PubMed DOI PMC

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8. PubMed

Passweg JR, Baldomero H, Chabannon C, Corbacioglu S, de la Camara R, Dolstra H, et al. Impact of the SARS-CoV-2 pandemic on hematopoietic cell transplantation and cellular therapies in Europe 2020: a report from the EBMT activity survey. Bone Marrow Transpl. 2022;57:742–52. doi: 10.1038/s41409-022-01604-x. PubMed DOI PMC

Passweg JR, Baldomero H, Ciceri F, Corbacioglu S, de la Camara R, Dolstra H, et al. Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey. Bone Marrow Transpl. 2023;58:647–58. doi: 10.1038/s41409-023-01943-3. PubMed DOI PMC

Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22:790–800. doi: 10.1016/S1470-2045(21)00139-X. PubMed DOI

Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N. Engl J Med. 2022;387:2220–31. doi: 10.1056/NEJMoa2206913. PubMed DOI

Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023;41:2238–47. doi: 10.1200/JCO.22.01725. PubMed DOI PMC

Gonzalez-Barca E, Boumendil A, Blaise D, Trneny M, Masszi T, Finel H, et al. Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) Bone Marrow Transpl. 2020;55:393–9. doi: 10.1038/s41409-019-0650-x. PubMed DOI

Chen YB, Lane AA, Logan B, Zhu X, Akpek G, Aljurf M, 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. doi: 10.1016/j.bbmt.2015.02.005. PubMed DOI PMC

Jagadeesh D, Majhail NS, He Y, Ahn KW, Litovich C, Ahmed S, et al. Outcomes of rituximab-BEAM versus BEAM conditioning regimen in patients with diffuse large B cell lymphoma undergoing autologous transplantation. Cancer. 2020;126:2279–87. doi: 10.1002/cncr.32752. PubMed DOI PMC

Bento L, Gutierrez A, Novelli S, Montoro J, Pinana JL, Lopez-Corral L, et al. Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study. Bone Marrow Transpl. 2021;56:1919–28. doi: 10.1038/s41409-021-01264-3. PubMed DOI

Fenske TS, Ahn KW, Graff TM, DiGilio A, Bashir Q, Kamble RT, et al. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. Br J Haematol. 2016;174:235–48. doi: 10.1111/bjh.14046. PubMed DOI PMC

Epperla N, Ahn KW, Khanal M, Litovich C, Ahmed S, Ghosh N, et al. Impact of reduced-intensity conditioning regimens on outcomes in diffuse large B cell lymphoma undergoing allogeneic transplantation. Transpl Cell Ther. 2021;27:58–66. doi: 10.1016/j.bbmt.2020.09.014. PubMed DOI PMC

Ghosh N, Ahmed S, Ahn KW, Khanal M, Litovich C, Aljurf M, et al. Association of reduced-intensity conditioning regimens with overall survival among patients with non-hodgkin lymphoma undergoing allogeneic transplant. JAMA Oncol. 2020;6:1011–8. doi: 10.1001/jamaoncol.2020.1278. PubMed DOI PMC

Robinson SP, Boumendil A, Finel H, Blaise D, Poire X, Nicolas-Virelizier E, et al. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party. Bone Marrow Transpl. 2016;51:365–71. doi: 10.1038/bmt.2015.286. PubMed DOI

Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1) Lancet Oncol. 2012;13:1250–9. doi: 10.1016/S1470-2045(12)70481-3. PubMed DOI

Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, et al. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas. J Clin Oncol. 2016;34:4015–22. doi: 10.1200/JCO.2016.67.2980. PubMed DOI

Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, et al. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017;18:1076–88. doi: 10.1016/S1470-2045(17)30444-8. PubMed DOI

Peniket AJ, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transpl. 2003;31:667–78. doi: 10.1038/sj.bmt.1703891. PubMed DOI

Doocey RT, Toze CL, Connors JM, Nevill TJ, Gascoyne RD, Barnett MJ, et al. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma. Br J Haematol. 2005;131:223–30. doi: 10.1111/j.1365-2141.2005.05755.x. PubMed DOI

Ghosh N, Karmali R, Rocha V, Ahn KW, DiGilio A, Hari PN, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a center for international blood and marrow transplant research analysis. J Clin Oncol. 2016;34:3141–9. doi: 10.1200/JCO.2015.66.3476. PubMed DOI PMC

Martinez C, Gayoso J, Canals C, Finel H, Peggs K, Dominietto A, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for hodgkin lymphoma: a registry study of the lymphoma working party of the european society for blood and marrow transplantation. J Clin Oncol. 2017;35:3425–32. doi: 10.1200/JCO.2017.72.6869. PubMed DOI

Dreger P, Sureda A, Ahn KW, Eapen M, Litovich C, Finel H, et al. PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL. Blood Adv. 2019;3:360–9. doi: 10.1182/bloodadvances.2018027748. PubMed DOI PMC

Bolanos-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N. Engl J Med. 2023;388:2338–48. doi: 10.1056/NEJMoa2215943. PubMed DOI PMC