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.

  • Original Article
  • Published:

Autografting

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre

Bone Marrow Transplantation volume 39, pages 41–47 (2007)Cite this article

Abstract

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3–161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M et al. German Hodgkin's Lymphoma Study Group; lymphoma working party of the European group for blood and marrow transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haematopoietic stem-cell transplantation for relapsed chemosensitive Hodkin's disease: a randomised trial. Lancet 2002; 359: 2065–2071.

    Article  CAS  PubMed  Google Scholar 

  2. Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A et al. Dose intensification with autologous bone-marrow transplantation in relapsed or resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051–1054.

    Article  CAS  PubMed  Google Scholar 

  3. Carella A, Carlier P, Congiu A, Occhini D, Meloni G, Anselmo AP et al. Nine years’ experience with ABMT in 128 patients with Hodgkin's disease: an Italian study group report. Leukemia 1991; 5 (Suppl 1): 68–71.

    PubMed  Google Scholar 

  4. Carella AM, Prencipe E, Pungolino E, Lerma E, Frassoni F, Rossi E et al. Twelve years experience with high-dose therapy and autologous stem cell transplantation for high-risk Hodgkin's disease patients in first remission after MOPP/ABVD chemotherapy. Leuk Lymph 1996; 21: 63–70.

    Article  CAS  Google Scholar 

  5. Wheeler C, Eickhoff C, Elias A, Ibrahim J, Ayash L, McCauley M et al. High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant 1997; 3: 98–106.

    CAS  PubMed  Google Scholar 

  6. Reece DE, Nevill TJ, Sayegh A, Spinelli JJ, Brockington DA, Barnett MJ et al. Regimen-related toxicity and non-relapse mortality with high-dose cyclophosphamide, carmustine (BCNU) and etoposide (VP16-213) (CBV) and CBV plus cisplatin (CBVP) followed by autologous stem cell transplantation in patients with Hodgkin's disease. Bone Marrow Transplant 1999; 23: 1131–1138.

    Article  CAS  PubMed  Google Scholar 

  7. Taylor PR, Jackson GH, Lennard AL, Lucraft H, Proctor SJ . Autologous transplantation in poor risk Hodgkin's disease using high dose melphalan/etoposide conditioning with non-cryopreserved marrow rescue. The Newcastle and Northern Region Lymphoma Group. Br J Cancer 1993; 67: 383–387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Waheed F, Kancherla R, Seiter K, Liu D, Qureshi Z, Hoang A et al. High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors. Leuk Lymph 2004; 45: 2253–2259.

    Article  CAS  Google Scholar 

  9. Gutierrez-Delgado F, Holmberg L, Hooper H, Petersdorf S, Press O, Maziarz R et al. Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation based regimen. Bone Marrow Transplant 2003; 32: 279–285.

    Article  CAS  PubMed  Google Scholar 

  10. Stewart DA, Guo D, Gluck S, Morris D, Chaudhry A, deMetz C et al. Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior to high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant 2000; 26: 383–388.

    Article  CAS  PubMed  Google Scholar 

  11. Sureda A, Constans M, Iriondo A, Arranz R, Caballero MD, Vidal MJ et al. Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Cooperative Group. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse. Ann Oncol 2005; 16: 625–633.

    Article  CAS  PubMed  Google Scholar 

  12. Czyz J, Dziadziuszko R, Knopinska-Posluszny W, Hellmann A, Kachel L, Holowiecki J et al. 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 2004; 15: 1222–1230.

    Article  CAS  PubMed  Google Scholar 

  13. Popat U, Hosing C, Saliba RM, Anderlini P, van Besien K, Przepiorka D et al. Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma. Bone Marrow Transplant 2004; 33: 1015–1023.

    Article  CAS  PubMed  Google Scholar 

  14. Czyz J, Szydlo R, Knopinska-Posluszny W, Hellmann A, Gozdzik J, Hansz J et al. Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy. Bone Marrow Transplant 2004; 33: 1225–1229.

    Article  CAS  PubMed  Google Scholar 

  15. Argiris A, Seropian S, Cooper DL . High-dose BEAM chemotherapy with autologous peripheral blood progenitor-cell transplantation for unselected patients with primary refractory or relapsed Hodgkin's disease. Ann Oncol 2000; 11: 665–672.

    Article  CAS  PubMed  Google Scholar 

  16. Hasenclever D, Diehl V . A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 1998; 339: 1506–1514.

    Article  CAS  PubMed  Google Scholar 

  17. Bierman PJ, Lynch JC, Bociek RG, Whalen VL, Kessinger A, Vose JM et al. The International Prognostic Factor Project score for advanced Hodgkin's disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation. Ann Oncol 2002; 13: 1370–1377.

    Article  CAS  PubMed  Google Scholar 

  18. Josting A, Rueffer U, Franklin J, Sieber M, Diehl V, Engert A . Prognostic factors and treatment outcome in primary progressive Hodgkin's lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood 2000; 96: 1280–1286.

    CAS  PubMed  Google Scholar 

  19. Josting A, Franklin J, May M, Koch P, Beykirch MK, Heinz J et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group. J Clin Oncol 2002; 20: 221–230.

    PubMed  Google Scholar 

  20. Lillington DM, Micallef IN, Carpenter E, Neat MJ, Amess JA, Matthews J et al. Genetic susceptibility to Hodgkin's disease and secondary neoplasia: FISH analysis reveals patients at high risk of developing secondary neoplasia. Ann Oncol 2002; 13 (Suppl 1): 40–43.

    Article  PubMed  Google Scholar 

  21. Wheeler C, Khurshid A, Ibrahim J, Elias A, Mauch P, Ault K et al. Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autlogous transplantation following cyclophosphamide, carmustine, and etoposide (CBV). Leuk Lymph 2001; 40: 499–509.

    Article  CAS  Google Scholar 

  22. Josting A, Rudolph C, Mapara M, Glossmann JP, Sienawski M, Sieber M et al. Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Ann Oncol 2005; 16: 116–123.

    Article  CAS  PubMed  Google Scholar 

  23. Glossmann JP, Josting A, Pfistner B, Paulus U, Engert A, German Hodgkin's Lymphoma Study Group (GHSG). A randomized trial of chemotherapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) plus peripheral stem cell transplantation (PBSCT) vs single-agent high-dose chemotherapy followed by BEAM plus PBSCT in patients with relapsed Hodgkin's disease (HD-R2). Ann Hematol 2002; 81: 424–429.

    Article  PubMed  Google Scholar 

  24. Schmitz N, Sureda A . The role of allogeneic stem-cell transplantation in Hodgkin's disease. Eur J Haematol Suppl 2005; 66: 146–149.

    Article  Google Scholar 

  25. Schnell R, Dietlein M, Staak JO, Borchmann P, Schomaecker K, Fischer T et al. Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol 2005; 23: 4669–4678.

    Article  CAS  PubMed  Google Scholar 

  26. Zheng B, Georgakis GV, Li Y, Bharti A, McConkey D, Aggarwal BB et al. Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-kappaB mutations or activation of the CD30, CD40, and RANK receptors. Clin Cancer Res 2004; 10: 3207–3215.

    Article  CAS  PubMed  Google Scholar 

  27. Younes A, Romaguera J, Hagemeister F, McLaughlin P, Rodriguez MA, Fiumara P et al. A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer 2003; 98: 310–314.

    Article  CAS  PubMed  Google Scholar 

  28. Sevilla J, Rodriguez A, Hernandez-Maraver D, de Bustos G, Aguado J, Ojeda E et al. Secondary acute myeloid leukemia and myelodysplasia after autologous peripheral blood progenitor cell trasnplantation. Ann Hematol 2002; 81: 11–15.

    Article  CAS  PubMed  Google Scholar 

  29. Lavoie JC, Connors JM, Phillips GL, Reece DE, Barnett MJ, Forrest DL et al. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood 2005; 106: 1473–1478.

    Article  CAS  PubMed  Google Scholar 

  30. Oddou S, Vey N, Viens P, Bardou VJ, Faucher C, Stoppa AM et al. Second neoplasms following high-dose chemotherapy and autologous stem cell transplantation for malignant lymphomas: a report of six cases in a cohort of 171 patients from a single institution. Leuk Lymph 1998; 31: 187–194.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Hammersmith Hospitals NHS Trust, Imperial College School of Medicine, London, UK

    J B Perz, C Giles, R Szydlo, D O'Shea, J Sanz, A Chaidos, S Wagner, J Davis, S Loaiza, D Marin, J Apperley, E Olavarria, A Rahemtulla, D Samson, D MacDonald & E J Kanfer

  2. Department of Histopathology, Hammersmith Hospitals NHS Trust, Imperial College School of Medicine, London, UK

    I Lampert & K Naresh

Authors
  1. J B Perz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Giles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R Szydlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D O'Shea
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Sanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Chaidos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Loaiza
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D Marin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J Apperley
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E Olavarria
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Rahemtulla
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. I Lampert
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. K Naresh
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D Samson
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. D MacDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. E J Kanfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E J Kanfer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perz, J., Giles, C., Szydlo, R. et al. LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre. Bone Marrow Transplant 39, 41–47 (2007). https://doi.org/10.1038/sj.bmt.1705544

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705544

Keywords

This article is cited by

Search

Advanced search

Quick links