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:

Lymphoma

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: A Prospective Australasian Leukaemia and Lymphoma Group Study

Bone Marrow Transplantation volume 35, pages 291–298 (2005)Cite this article

Summary:

This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III–IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P=0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study.

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

Similar content being viewed by others

References

  1. Armitage JO . Bone marrow transplantation. N Engl J Med 1994; 330: 827–838.

    Article  CAS  PubMed  Google Scholar 

  2. Wadhwa P, Shina DC, Schenkein D, Lazarus HM . Should involved-field radiation therapy be used as an adjunct to lymphoma autotransplantation? Bone Marrow Transplant 2002; 29: 183–189.

    Article  CAS  PubMed  Google Scholar 

  3. Mundt AJ, Sibley G, Williams S et al. Patterns of failure following high-dose chemotherapy and autologous bone marrow transplantation with involved field radiotherapy for relapsed/refractory Hodgkin's disease. Int J Radiat Oncol Biol Phys 1995; 33: 261–270.

    Article  CAS  PubMed  Google Scholar 

  4. Rapoport AP, Rowe JM, Kouides PA et al. One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome. J Clin Oncol 1993; 11: 2351–2361.

    Article  CAS  PubMed  Google Scholar 

  5. Crump M, Smith AM, Brandwein J et al. High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. J Clin Oncol 1993; 11: 704–711.

    Article  CAS  PubMed  Google Scholar 

  6. Philip T, Guglielmi C, Hagenbeek A 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: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  7. Constine L, Brassachio R, Rapaport A, Rowe J . Radiotherapy to previously involved sites after autotransplantation for lymphoma and Hodgkin's disease. Proc Am Soc Clin Oncol 1995; 14: 394.

    Google Scholar 

  8. Poen JC, Hoppe RT, Horning SJ . High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: the impact of involved field radiotherapy on patterns of failure and survival. Int J Radiat Oncol Biol Phys 1996; 36: 3–12.

    Article  CAS  PubMed  Google Scholar 

  9. Fouillard L, Laporte JP, Labopin M et al. Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation-results of a retrospective analysis on 120 patients autografted in a single institution. J Clin Oncol 1998; 16: 2803–2816.

    Article  CAS  PubMed  Google Scholar 

  10. Lancet JE, Rapoport AP, Brasacchio R et al. Autotransplantation for relapsed or refractory Hodgkin's disease: long-term follow-up and analysis of prognostic factors. Bone Marrow Transplant 1998; 22: 265–271.

    Article  CAS  PubMed  Google Scholar 

  11. Vose JM, Zhang MJ, Rowlings PA et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001; 19: 406–413.

    Article  CAS  PubMed  Google Scholar 

  12. Friedberg JW, Neuberg D, Monson E et al. The impact of external beam radiation therapy prior to autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma. Biol Blood Marrow Transplant 2001; 7: 446–453.

    Article  CAS  PubMed  Google Scholar 

  13. Weaver CH, Appelbaum FR, Petersen FB et al. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy. J Clin Oncol 1993; 11: 1329–1335.

    Article  CAS  PubMed  Google Scholar 

  14. Yahalom J, Gulati SC, Toia M et al. Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease. J Clin Oncol 1993; 11: 1062–1070.

    Article  CAS  PubMed  Google Scholar 

  15. Pezner RD, Nademanee A, Niland JC et al. Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens. Radiother Oncol 1995; 34: 23–29.

    Article  CAS  PubMed  Google Scholar 

  16. Reece DE, Barnett MJ, Connors JM 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: 1871–1879.

    Article  CAS  PubMed  Google Scholar 

  17. Price A, Cunningham D, Horwich A, Brada M . Haematological toxicity of radiotherapy following high-dose chemotherapy and autologous bone marrow transplantation in patients with recurrent Hodgkin's disease. Eur J Cancer 1994; 30A: 903–907.

    Article  CAS  PubMed  Google Scholar 

  18. National Cancer Institute. National Cancer Institute Common Toxicity Criteria Version 2.0, Publish Date April 30, 1999. Available for download from http://ctep.cancer.gov.reporting/ctc.html.

  19. CYTEL Software Corporation. StatXact 5.0.3. CYTEL Software Corporation, Cambridge, MA, 2001.

  20. SPSS Inc. SPSS for Windows 11.0.1. SPSS Inc., Chicago, IL, 2001.

  21. MathSoft Inc. S-PLUS 2000. MathSoft, Inc., Seattle, WA, 1999.

  22. Yahalom J . Integrating radiotherapy into bone marrow transplantation programs for Hodgkin's disease. Int J Radiat Oncol Biol Phys 1995; 33: 525–528.

    Article  CAS  PubMed  Google Scholar 

  23. Yahalom J . High-dose chemotherapy and radiotherapy with bone marrow transplantation in the management of the non-hodgkin's lymphomas. Semin Radiat Oncol 1995; 5: 316–330.

    Article  CAS  PubMed  Google Scholar 

  24. Hoppe RT . Radiation therapy as a component of high-dose salvage strategies in Hodgkin's disease. Ann Oncol 1998; 9 (Suppl 5): S87–S90.

    Article  PubMed  Google Scholar 

  25. Philip T, Armitage JO, Spitzer G et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987; 316: 1493–1498.

    Article  CAS  PubMed  Google Scholar 

  26. Freedman AS, Takvorian T, Anderson KC et al. Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse. J Clin Oncol 1990; 8: 784–791.

    Article  CAS  PubMed  Google Scholar 

  27. Petersen FB, Appelbaum FR, Hill R et al. Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle. J Clin Oncol 1990; 8: 638–647.

    Article  CAS  PubMed  Google Scholar 

  28. Freedman AS, Neuberg D, Mauch P et al. Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 1999; 94: 3325–3333.

    CAS  PubMed  Google Scholar 

  29. Apostolidis J, Foran JM, Johnson PW et al. Patterns of outcome following recurrence after myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma. J Clin Oncol 1999; 17: 216–221.

    Article  CAS  PubMed  Google Scholar 

  30. Reece DE, Connors JM, Spinelli JJ et al. Intensive therapy with cyclophosphamide, carmustine, etoposide +/− cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood 1994; 83: 1193–1199.

    CAS  PubMed  Google Scholar 

  31. Roach III M, Kapp DS, Rosenberg SA, Hoppe RT . Radiotherapy with curative intent: an option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease. J Clin Oncol 1987; 5: 550–555.

    Article  PubMed  Google Scholar 

  32. Kirkove C, Timothy AR . Radiotherapy as salvage treatment in patients with Hodgkin's disease or non-Hodgkin's lymphoma relapsing after initial chemotherapy. Hematol Oncol 1991; 9: 163–167.

    Article  CAS  PubMed  Google Scholar 

  33. Lohri A, Barnett M, Fairey RN et al. Outcome of treatment of first relapse of Hodgkin's disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988. Blood 1991; 77: 2292–2298.

    CAS  PubMed  Google Scholar 

  34. Brada M, Eeles R, Ashley S et al. Salvage radiotherapy in recurrent Hodgkin's disease. Ann Oncol 1992; 3: 131–135.

    Article  CAS  PubMed  Google Scholar 

  35. Leigh BR, Fox KA, Mack CF et al. Radiation therapy salvage of Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Biol Phys 1993; 27: 855–862.

    Article  CAS  PubMed  Google Scholar 

  36. Uematsu M, Tarbell NJ, Silver B et al. Wide-field radiation therapy with or without chemotherapy for patients with Hodgkin disease in relapse after initial combination chemotherapy. Cancer 1993; 72: 207–212.

    Article  CAS  PubMed  Google Scholar 

  37. Pezner RD, Lipsett JA, Vora N, Forman SJ . Radical radiotherapy as salvage treatment for relapse of Hodgkin's disease initially treated by chemotherapy alone: prognostic significance of the disease-free interval. Int J Radiat Oncol Biol Phys 1994; 30: 965–970.

    Article  CAS  PubMed  Google Scholar 

  38. Diehl LF, Thompson J, Andejeski Y . Salvage radiotherapy following chemotherapy failure in Hodgkin's disease. Proc Am Soc Clin Oncol 1994; 13: 390.

    Google Scholar 

  39. MacMillan CH, Bessell EM . The effectiveness of radiotherapy for localized relapse in patients with Hodgkin's disease (IIB–IVB) who obtained a complete response with chemotherapy alone as initial treatment. Clin Oncol (R Coll Radiol) 1994; 6: 147–150.

    Article  CAS  Google Scholar 

  40. O'Brien PC, Parnis FX . Salvage radiotherapy following chemotherapy failure in Hodgkin's disease – what is its role? Acta Oncol 1995; 34: 99–104.

    Article  CAS  PubMed  Google Scholar 

  41. Wirth A, Corry J, Laidlaw C et al. Salvage radiotherapy for Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Biol Phys 1997; 39: 599–607.

    Article  CAS  PubMed  Google Scholar 

  42. Josting A, Rueffer U, Franklin J et al. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood 2000; 96: 1280–1286.

    CAS  PubMed  Google Scholar 

  43. Vose JM, Bierman PJ, Anderson JR et al. Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up. Blood 1992; 80: 2142–2148.

    CAS  PubMed  Google Scholar 

  44. Toren A, Nagler R, Nagler A . Involved field radiation post autologous stem cell transplantation in lymphoma patients is associated with major haematological toxicities. Med Oncol 1998; 15: 113–118.

    Article  CAS  PubMed  Google Scholar 

  45. Abrams RA, Liu PJ, Ambinder RF et al. Hodgkin and non-Hodgkin lymphoma: local-regional radiation therapy after bone marrow transplantation. Radiology 1997; 203: 865–870.

    Article  CAS  PubMed  Google Scholar 

  46. Kaiser U, Uebelacker I, Abel U et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for ‘aggressive’ lymphoma. J Clin Oncol 2002; 20: 4413–4419.

    Article  CAS  PubMed  Google Scholar 

  47. Tsang RW, Gospodarowicz MK, Sutcliffe SB et al. Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group. Eur J Cancer 1999; 35: 73–78.

    Article  CAS  PubMed  Google Scholar 

  48. Chadha M, Shank B, Fuks Z et al. Improved survival of poor prognosis diffuse histiocytic (large cell) lymphoma managed with sequential induction chemotherapy, ‘boost’ radiation therapy, and autologous bone marrow transplantation. Int J Radiat Oncol Biol Phys 1988; 14: 407–415.

    Article  CAS  PubMed  Google Scholar 

  49. Dawson LA, Saito NG, Ratanatharathorn V et al. Phase I study of involved-field radiotherapy preceding autologous stem cell transplantation for patients with high-risk lymphoma or Hodgkin's disease. Int J Radiat Oncol Biol Phys 2004; 59: 208–218.

    Article  PubMed  Google Scholar 

  50. von der Maase H, Overgaard J, Vaeth M . Effect of cancer chemotherapeutic drugs on radiation-induced lung damage in mice. Radiother Oncol 1986; 5: 245–257.

    Article  CAS  PubMed  Google Scholar 

  51. Yan R, Peters LJ, Travis EL . Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow. Radiother Oncol 1991; 21: 149–156.

    Article  CAS  PubMed  Google Scholar 

  52. Theuws JC, Muller SH, Seppenwoolde Y et al. Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphoma: a follow-up study. J Clin Oncol 1999; 17: 3091–3100.

    Article  CAS  PubMed  Google Scholar 

  53. Sureda A, Arranz R, Iriondo A et al. Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 2001; 19: 1395–1404.

    Article  CAS  PubMed  Google Scholar 

  54. Chao MW, Wirth A, Ryan G et al. Radiation myelopathy following transplantation and radiotherapy for non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 1998; 41: 1057–1061.

    Article  CAS  PubMed  Google Scholar 

  55. Krishnan A, Bhatia S, Slovak ML et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 2000; 95: 1588–1593.

    CAS  PubMed  Google Scholar 

  56. Brincker H, Bentzen SM . A re-analysis of available dose-response and time–dose data in Hodgkin's disease. Radiother Oncol 1994; 30: 227–230.

    Article  CAS  PubMed  Google Scholar 

  57. Wilder RB, Tucker SL, Ha CS et al. Dose–response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy. Int J Radiat Oncol Biol Phys 2001; 49: 17–22.

    Article  CAS  PubMed  Google Scholar 

  58. Wilder RB, Rodriguez MA, Tucker SL et al. Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas. Int J Radiat Oncol Biol Phys 2001; 50: 743–749.

    Article  CAS  PubMed  Google Scholar 

  59. Mundt AJ, Connell PP, Mansur DB . What is the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy and adjuvant radiation therapy? Radiat Oncol Invest 1999; 7: 353–359.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the clinicians and data managers in the participating centres for their contribution and Cathy Faull for secretarial assistance.

Author information

Authors and Affiliations

  1. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia

    A Wirth

  2. Haematology Service, Peter MacCallum Cancer Centre, Victoria, Australia

    H M Prince & M Wolf

  3. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victoria, Australia

    J M Stone & J Matthews

  4. Institute of Haematology, Royal Prince Alfred Hospital, New South Wales, Australia

    J Gibson

  5. Murray Valley Radiation Oncology, Victoria, Australia

    C Macleod

  6. Bone Marrow Transplant Service, Royal Melbourne Hospital, Victoria, Australia

    J Szer & A Grigg

  7. Haematology Department, Royal Adelaide Hospital, South Australia, Australia

    B To

  8. Department of Radiotherapy, Royal Adelaide Hospital, South Australia, Australia

    D Roos

  9. Bone Marrow Transplant Service, Alfred Hospital, Victoria, Australia

    A P Schwarer

  10. Department of Radiotherapy, Alfred Hospital, Victoria, Australia

    S Davis

Authors
  1. A Wirth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H M Prince
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J M Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Matthews
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Macleod
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Szer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Grigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. B To
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D Roos
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A P Schwarer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Australasian Leukaemia and Lymphoma Group

Corresponding author

Correspondence to A Wirth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wirth, A., Prince, H., Wolf, M. et al. Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: A Prospective Australasian Leukaemia and Lymphoma Group Study. Bone Marrow Transplant 35, 291–298 (2005). https://doi.org/10.1038/sj.bmt.1704759

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704759

Keywords

Search

Advanced search

Quick links