Skip to main content
SpringerLink
Log in

High-dose chemotherapy followed by autologous stem cell transplantation for patients with refractory/relapsed classical Hodgkin lymphoma: a single center experience from China

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

To evaluate the outcomes of refractory/relapsed cHL patients after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in Beijing Cancer hospital and to identify the prognostic risk factors. We retrospectively analyzed 115 relapsed/refractory cHL patients who accepted HDCT and ASCT in our cancer center and had complete follow-up data from April 2000 to May 2017. Ages of these 115 patients at ASCT ranged from 14 to 63 (median age 28). Forty-four (38.3%) patients achieved CR and 50 (43.5%) patients achieved PR before ASCT. Thirty-seven (48.7%) patients of those 76 patients who did PET-CT before ASCT had negative PET-CT scans. The median follow-up time was 72 months. A total of 23 patients died in our study. The 5-year OS and PFS rates of all patients after ASCT were 78.7% and 53%, respectively. The 5-year OS rates after ASCT of patients who were in CR or PR or less than PR status before ASCT were 92.8%, 68.2%, and 76.2%, respectively (log-rank = 2.913, p = 0.233). And their 5-year PFS rates after ASCT were 69.2%, 54.2%, and 18.5%, respectively (log-rank = 13.615, p = 0.001). Univariate analysis revealed that ECOG (p = 0.010; hazard ratio = 1.578), disease status before ASCT (CR: p = 0.001; hazard ratio = 0.227) and after ASCT (CR: p < 0.001; hazard ratio = 0.154), and PET-CT results after ASCT (p = 0.023; hazard ratio = 0.438) significantly impact patients’ PFS while number of pretransplant salvage chemotherapy (p = 0.037; hazard ratio = 2.521), radiotherapy (p = 0.046; hazard ratio = 0.423), and disease status after ASCT (CR: p = 0.010; hazard ratio = 0.197) significantly affected patients’ OS. Multivariate analysis shown only disease status before ASCT (p = 0.002) had significant impact on PFS and disease status after ASCT (p = 0.021) had significant impact on OS. R/R HL patients can still obtain long-term PFS after HDCT and ASCT and disease status before ASCT was the most significant prognostic factor for PFS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A (2016) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 128(12):1562–1566. https://doi.org/10.1182/blood-2016-02-699850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH, KEYNOTE-087 (2017) Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 35(19):2125–2132. https://doi.org/10.1200/JCO.2016.72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, de Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM (2018) Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 Trial. J Clin Oncol 36(14):1428–1439. https://doi.org/10.1200/JCO.2017.76.0793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V, German Hodgkin's Lymphoma Study Group, Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (2002) Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 359(9323):2065–2071

    Article  CAS  Google Scholar 

  5. Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A, Chopra R, Milligan D, Hudson GV (1993) Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet. 341(8852):1051–1054

    Article  CAS  Google Scholar 

  6. Fermé C, Mounier N, Diviné M, Brice P, Stamatoullas A, Reman O, Voillat L, Jaubert J, Lederlin P, Colin P, Berger F, Salles G (2002) Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial. J Clin Oncol 20(2):467–475

    PubMed  Google Scholar 

  7. Rimner A, Lovie S, Hsu M, Chelius M, Zhang Z, Chau K, Moskowitz AJ, Matasar M, Moskowitz CH, Yahalom J (2017) Accelerated total lymphoid irradiation-containing salvage regimen for patients with refractory and relapsed Hodgkin lymphoma: 20 years of experience. Int J Radiat Oncol Biol Phys 97(5):1066–1076. https://doi.org/10.1016/j.ijrobp.2017.01.222

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32(27):3059–3068

    Article  Google Scholar 

  9. Meignan M, Barrington S, Itti E, Gallamini A, Haioun C, Polliack A (2014) Report on the 4th International Workshop on Positron Emission Tomography in Lymphoma held inMenton, France, 3-5 October 2012. Leuk Lymphoma 55(1):31–37. https://doi.org/10.3109/10428194.2013.802784

    Article  PubMed  Google Scholar 

  10. Lim SH, Johnson PWM (2018) Optimizing therapy in advanced-stage Hodgkin lymphoma. Blood. 131(15):1679–1688. https://doi.org/10.1182/blood-2017-09-772640

    Article  CAS  PubMed  Google Scholar 

  11. Bröckelmann PJ, Sasse S, Engert A (2018) Balancing risk and benefit in early-stage classical Hodgkin lymphoma. Blood. 131(15):1666–1678. https://doi.org/10.1182/blood-2017-10-772665

    Article  CAS  PubMed  Google Scholar 

  12. Giulino-Roth L, O'Donohue T, Chen Z, Trippett TM, Klein E, Kernan NA, Kobos R, Prockop SE, Scaradavou A, Shukla N, Steinherz PG, Moskowitz AJ, Moskowitz CH, Boulad F (2018) Outcome of children and adolescents with relapsed Hodgkin lymphoma treated with high-dose therapy and autologous stem cell transplantation: the Memorial Sloan Kettering Cancer Center experience. Leuk Lymphoma 59(8):1861–1870. https://doi.org/10.1080/10428194.2017.1403601

    Article  CAS  PubMed  Google Scholar 

  13. Bröckelmann PJ, Müller H, Casasnovas O, Hutchings M, von Tresckow B, Jürgens M, McCall S, Morschhauser F, Fuchs M, Borchmann P, Moskowitz CH, Engert A (2017) Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma. Ann Oncol 28(6):1352–1358. https://doi.org/10.1093/annonc/mdx072

    Article  PubMed  Google Scholar 

  14. Adams HJ, Kwee TC (2016) Prognostic value of pretransplant FDG-PET in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation: systematic review and meta-analysis. Ann Hematol 95(5):695–706. https://doi.org/10.1007/s00277-016-2619-9

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sucak GT, Özkurt ZN, Suyani E, Yaşar DG, Akdemir ÖÜ, Aki Z, Yeğin ZA, Yağci M, Kapucu ÖL (2011) Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol 90(11):1329–1336. https://doi.org/10.1007/s00277-011-1209-0

    Article  PubMed  Google Scholar 

  16. Smeltzer JP, Cashen AF, Zhang Q, Homb A, Dehdashti F, Abboud CN, Dipersio JF, Stockerl-Goldstein KE, Uy GL, Vij R, Westervelt P, Bartlett NL, Fehniger TA (2011) Prognostic significance of FDG-PET in relapsed or refractory classical Hodgkin lymphoma treated with standard salvage chemotherapy and autologous stem cell transplantation. Biol Blood Marrow Transplant 17(11):1646–1652. https://doi.org/10.1016/j.bbmt.2011.04.011

    Article  PubMed  PubMed Central  Google Scholar 

  17. Procházka V, Gawande RS, Cayci Z, Froelich JW, Cao Q, Wilke C, Dusenbery K, Weisdorf DJ, Bachanova V (2018) Positron emission tomography-based assessment of metabolic tumor volume predicts survival after autologous hematopoietic cell transplantation for Hodgkin lymphoma. Biol Blood Marrow Transplant 24(1):64–70. https://doi.org/10.1016/j.bbmt.2017.09.006

    Article  PubMed  Google Scholar 

  18. Chen YB, Lane AA, Logan B, Zhu X, Akpek G, Aljurf M, Artz A, Bredeson CN, Cooke KR, Ho VT, Lazarus HM, Olsson R, Saber W, McCarthy P, Pasquini MC (2015) Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant 21(6):1046–1053. https://doi.org/10.1016/j.bbmt.2015.02.005

    Article  PubMed  PubMed Central  Google Scholar 

  19. Olivieri J, Mosna F, Pelosini M et al (2018) 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 Transplant 24(9):1814–1822. https://doi.org/10.1016/j.bbmt.2018.05.018

    Article  PubMed  Google Scholar 

  20. William BM, Loberiza FR Jr, Whalen V et al (2013) Impact of conditioning regimen on outcome of 2-year disease-free survivors of autologous stem cell transplantation for Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 13(4):417–423. https://doi.org/10.1016/j.clml.2013.03.009

    Article  PubMed  Google Scholar 

  21. Grisariu S, Shapira MY, Or R et al (2018 Apr) Thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan (TECAM) conditioning regimen for autologous stem cell transplantation in lymphoma. Clin Lymphoma Myeloma Leuk 18(4):272–279. https://doi.org/10.1016/j.clml.2018.02.008

    Article  PubMed  Google Scholar 

  22. Nieto Y, Thall PF, Ma J, Valdez BC, Ahmed S, Anderlini P, Popat U, Jones RB, Shpall EJ, Hosing C, Qazilbash M, Kebriaei P, Alousi A, Timmons M, Gulbis A, Myers A, Oki Y, Fanale M, Dabaja B, Pinnix C, Milgrom S, Champlin R, Andersson BS (2018) Phase II trial of high-dose gemcitabine/busulfan/melphalan with autologous stem cell transplantation for primary refractory or poor-risk relapsed Hodgkin lymphoma. Biol Blood Marrow Transplant 24(8):1602–1609. https://doi.org/10.1016/j.bbmt.2018.02.020

    Article  CAS  PubMed  Google Scholar 

  23. Milgrom SA, Jauhari S, Plastaras JP, Nieto Y, Dabaja BS, Pinnix CC, Smith GL, Allen PK, Lukens JN, Maity A, Oki Y, Fanale MA, Nasta SD (2017) A multi-institutional analysis of peritransplantation radiotherapy in patients with relapsed/refractory Hodgkin lymphoma undergoing autologous stem cell transplantation. Cancer. 123(8):1363–1371. https://doi.org/10.1002/cncr.30482

    Article  CAS  PubMed  Google Scholar 

  24. Kahn S, Flowers C, Xu Z et al (2011) Does the addition of involved field radiotherapy to high-dose chemotherapy and stem cell transplantation improve outcomes for patients with relapsed/refractory Hodgkin lymphoma? Int J Radiat Oncol Biol Phys 81:175–180. https://doi.org/10.1016/j.ijrobp.2010.05.010

    Article  PubMed  Google Scholar 

  25. Biswas T, Culakova E, Friedberg JW, Kelly JL, Dhakal S, Liesveld J, Phillips GL, Constine LS (2012) Involved field radiation therapy following high dose chemotherapy and autologous stem cell transplant benefits local control and survival in refractory or recurrent Hodgkin lymphoma. Radiother Oncol 103:367–372. https://doi.org/10.1016/j.radonc.2011.12.031

    Article  PubMed  Google Scholar 

  26. Levis M, Piva C, Filippi AR et al (2017) Potential benefit of involved-field radiotherapy for patients with relapsed-refractory Hodgkin’s lymphoma with incomplete response before autologous stem cell transplantation. Clin Lymphoma Myeloma Leuk 17(1):14–22. https://doi.org/10.1016/j.clml.2016.09.008

    Article  PubMed  Google Scholar 

  27. Czyz J, Dziadziuszko R, Knopinska-Postuszuy W et al (2004) Outcome and prognostic factors in advanced Hodgkin’s disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients. Ann Oncol 15(8):1222–1230

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank M.S. Lan Mi for the support in statistical method.

Funding

This work was supported by the Beijing Medical and Health Foundation (No. 2221-16-157).

Author information

Authors and Affiliations

  1. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China

    Yan Xie, Xiaopei Wang, Xin Leng, Wen Zheng, Lingyan Ping, Chen Zhang, Weiping Liu, Lijuan Deng, Meng Wu, Yuqin Song & Ju Zhu

Authors
  1. Yan Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaopei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lingyan Ping
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weiping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lijuan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Meng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuqin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ju Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ju Zhu.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xie, Y., Wang, X., Leng, X. et al. High-dose chemotherapy followed by autologous stem cell transplantation for patients with refractory/relapsed classical Hodgkin lymphoma: a single center experience from China. Ann Hematol 99, 549–555 (2020). https://doi.org/10.1007/s00277-019-03812-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-019-03812-w

Keywords

Search

Navigation