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Lymphoma

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma

Summary:

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1–19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27–42) and 29% (95% CI 22–36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

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References

  1. Urba WJ, Longo DL . Hodgkin's disease. N Engl J Med 1992; 326: 678–687.

    Article  CAS  Google Scholar 

  2. Specht L, Gray RG, Clarke MJ, Peto R . Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients International Hodgkin's Disease Collaborative Group. J Clin Oncol 1998; 16: 830–843.

    Article  CAS  Google Scholar 

  3. Hoppe RT, Coleman CN, Cox RS et al. The management of stage I–II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience. Blood 1982; 59: 455–465.

    CAS  PubMed  Google Scholar 

  4. Mauch P, Tarbell N, Weinstein H et al. Stage IA and IIA supradiaphragmatic Hodgkin's disease: prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation. J Clin Oncol 1988; 6: 1576–1583.

    Article  CAS  Google Scholar 

  5. Vlachaki MT, Ha CS, Hagemeister FB et al. Long-term outcome of treatment for Ann Arbor stage 1 Hodgkin's disease: patterns of failure, late toxicity and second malignancies. Int J Radiat Oncol Biol Phys 1997; 39: 609–616.

    Article  CAS  Google Scholar 

  6. Farah R, Ultmann J, Griem M et al. Extended mantle radiation therapy for pathologic stage I and II Hodgkin's disease. J Clin Oncol 1988; 6: 1047–1052.

    Article  CAS  Google Scholar 

  7. Longo DL, Young RC, Wesley M et al. Twenty years of MOPP therapy for Hodgkin's disease. J Clin Oncol 1986; 4: 1295–1306.

    Article  CAS  Google Scholar 

  8. Glick JH, Young ML, Harrington D et al. MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial. J Clin Oncol 1998; 16: 19–26.

    Article  CAS  Google Scholar 

  9. Canellos GP, Anderson JR, Propert KJ et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992; 327: 1478–1484.

    Article  CAS  Google Scholar 

  10. Connors JM, Klimo P, Adams G et al. Treatment of advanced Hodgkin's disease with chemotherapy–comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. [Published erratum appears in J Clin Oncol 15:2762, 1997.] J Clin Oncol 1997; 15: 1638–1645.

    Article  CAS  Google Scholar 

  11. Santoro A, Viviani S, Villarreal CJ et al. Salvage chemotherapy in Hodgkin's disease irradiation failures: superiority of doxorubicin-containing regimens over MOPP. Cancer Treat Rep 1986; 70: 343–348.

    CAS  PubMed  Google Scholar 

  12. Canellos GP, Young RC, Berard CW, DeVita VT . Combination chemotherapy and survival in advanced Hodgkin's disease. Arch Intern Med 1973; 131: 388–390.

    Article  CAS  Google Scholar 

  13. Timothy AR, Sutcliffe SB, Wrigley PF, Jones AE . Hodgkin's disease: combination chemotherapy for relapse following radical radiotherapy. Int J Radiat Oncol Biol Phys 1979; 5: 165–169.

    Article  CAS  Google Scholar 

  14. 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  Google Scholar 

  15. Mauch P, Tarbell N, Skarin A et al. Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy. J Clin Oncol 1987; 5: 544–549.

    Article  CAS  Google Scholar 

  16. Roach 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Longo DL, Duffey PL, Young RC et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure. J Clin Oncol 1992; 10: 210–218.

    Article  CAS  Google Scholar 

  19. Santoro A, Bonfante V, Bonadonna G . Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease. Ann Intern Med 1982; 96: 139–143.

    Article  CAS  Google Scholar 

  20. Tannir N, Hagemeister F, Velasquez W, Cabanillas F . Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol 1983; 1: 432–439.

    Article  CAS  Google Scholar 

  21. Bierman PJ, Bagin RG, Jagannath S et al. High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients. Ann Oncol 1993; 4: 767–773.

    Article  CAS  Google Scholar 

  22. Yuen AR, Rosenberg SA, Hoppe RT et al. Comparison between conventional salvage therapy and high dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood 1997; 89: 814–822.

    CAS  Google Scholar 

  23. Jagannath S, Armitage JO, Dicke KA et al. Prognostic factors for response and survival after high-dose cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 1989; 7: 179–185.

    Article  CAS  Google Scholar 

  24. Armitage JO, Bierman PJ, Vose JM et al. Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease. Am J Med 1991; 91: 605–611.

    Article  CAS  Google Scholar 

  25. Andre M, Henry-Amar M, Pico JL et al. Comparison of high-dose therapy and autologous stem cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Societe Francaise de Greffe de Moelle. J Clin Oncol 1999; 17: 222–229.

    Article  CAS  Google Scholar 

  26. 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. [Published erratum appears in J Clin Oncol 10:170, 1992.] J Clin Oncol 1991; 9: 1871–1879.

    Article  CAS  Google Scholar 

  27. Chopra R, McMillan AK, Linch DC et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients. Blood 1993; 81: 1137–1145.

    CAS  Google Scholar 

  28. Horning SJ, Chao NJ, Negrin RS et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood 1997; 89: 801–813.

    CAS  Google Scholar 

  29. 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  Google Scholar 

  30. Nademanee A, O'Donnell MR, Snyder DS et al. High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. Blood 1995; 85: 1381–1390.

    CAS  Google Scholar 

  31. Wheeler C, Eickhoff C, Elias A 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  Google Scholar 

  32. Burns LJ, Daniels KA, McGlave PB et al. Autologous stem cell transplantation for refractory and relapsed Hodgkin's disease: factors predictive of prolonged survival. Bone Marrow Transplant 1995; 16: 13–18.

    CAS  Google Scholar 

  33. O'Brien ME, Milan S, Cunningham D et al. High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease–a pragmatic prognostic index. Br J Cancer 1996; 73: 1272–1277.

    Article  CAS  Google Scholar 

  34. 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  Google Scholar 

  35. 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  Google Scholar 

  36. Baker KS, Gordon BG, Gross TG et al. Autologous hematopoietic stem cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents. J Clin Oncol 1999; 17: 825–831.

    Article  CAS  Google Scholar 

  37. 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 Español de Linfomas/Transplante Autólogo de Medulla Ósea Spanish cooperative Group. J Clin Oncol 2001; 19: 1395–1404.

    Article  CAS  Google Scholar 

  38. Jones RJ, Piantadosi S, Mann RB et al. High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 1990; 8: 527–837.

    Article  CAS  Google Scholar 

  39. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  40. Prentice RL, Kalbfleisch JD, Peterson Jr AV et al. The analysis of failure times in the presence of competing risks. Biometrics 1978; 34: 541–554.

    Article  CAS  Google Scholar 

  41. Cox D . Regression models and life tables. J Roy Stat Soc (B) 1972; 34: 187.

    Google Scholar 

  42. StataCorp. Stata Statistical Software: release 7.0. College Station, TX: Stata Corporation, 2001.

  43. Bierman, PJ, Lynch JC, Bociek RG et al. The International Prognostic factors 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  Google Scholar 

  44. Brice P, Bouabdallah R, Moreau P et al. Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin's disease: analysis of 280 patients from the French registry. Societe Francaise de Greffe de Moelle. Bone Marrow Transplant 1997; 20: 21–26.

    Article  CAS  Google Scholar 

  45. Reece D . Should high risk patients with Hodgkin's disease be singled out for heavier therapeutic regimens while low risk patients are spared such therapies? Leuk Lymphoma 1995; 15 (suppl. 1): 19–21.

    Article  Google Scholar 

  46. Desch CE, Lasala MR, Smith TJ, Hillner BE . The optimal timing of autologous bone marrow transplantation in Hodgkin's disease patients after a chemotherapy relapse. J Clin Oncol 1992; 10: 200–209.

    Article  CAS  Google Scholar 

  47. Darrington DL, Vose JM, Anderson JR et al. Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. J Clin Oncol 1994; 12: 2527–2534.

    Article  CAS  Google Scholar 

  48. Abrahamsen JF, Andersen A, Hannisdal E et al. Second malignancies after treatment of Hodgkin's disease: the influence of treatment, follow-up time, and age. J Clin Oncol 1993; 11: 255–261.

    Article  CAS  Google Scholar 

  49. Zulian GB, Mirimanoff RO . Ten-year nodular sclerosis Hodgkin's disease and second malignancies. Eur J Cancer Clin Oncol 1989; 25: 659–665.

    Article  CAS  Google Scholar 

  50. Tucker MA, Coleman CN, Cox RS et al. Risk of second cancers after treatment for Hodgkin's disease. N Engl J Med 1988; 318: 76–81.

    Article  CAS  Google Scholar 

  51. Sont JK, van Stiphout WA, Noordijk EM et al. Increased risk of second cancers in managing Hodgkins disease: the 20-year Leiden experience. Ann Hematol 1992; 65: 213–218.

    Article  CAS  Google Scholar 

  52. Josting A, Wiedenmann S, Franklin J et al. Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol 2003; 21: 3440–3446.

    Article  Google Scholar 

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Correspondence to C Hosing.

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Popat, U., Hosing, C., Saliba, R. 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 33, 1015–1023 (2004). https://doi.org/10.1038/sj.bmt.1704483

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