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Allografting

Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation

Bone Marrow Transplantation volume 35, pages 971–977 (2005)Cite this article

Summary:

In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910 mg/m2 prior to melphalan 200 mg/m2. Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P=0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P=0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14% of the amifostine and control groups, respectively (P=0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to high-dose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis.

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References

  1. Hjorth M, Holmberg E, Rodjer S et al. Survival in conventionally treated younger (<60 years) multiple myeloma patients: no improvement during two decades. Nordic Myeloma Study Group (NMSG). Eur J Haematol 1999; 62: 271–277.

    Article  CAS  PubMed  Google Scholar 

  2. McElwain TJ, Powles RL . High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983; 2: 822–824.

    Article  CAS  PubMed  Google Scholar 

  3. Selby PJ, McElwain TJ, Nandi AC et al. Multiple myeloma treated with high dose intravenous melphalan. Br J Haematol 1987; 66: 55–62.

    Article  CAS  PubMed  Google Scholar 

  4. Attal M, Harousseau JL, Stoppa AM et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome (see comments). N Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  5. Child JA, Morgan GJ, Davies FE et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  6. Bjorkstrand B, Ljungman P, Bird JM et al. Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation. Stem Cells 1995; 13: 140–146.

    Article  PubMed  Google Scholar 

  7. Moreau P, Facon T, Attal M et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial (comment). Blood 2002; 99: 731–735.

    Article  CAS  PubMed  Google Scholar 

  8. de Fraine AD, Diekman JL, Gaynor GM . In: de Fraine AD, Diekman JL, Gaynor GM (eds). Clinical Guidelines for the Use of Antineoplastic Agents, 3rd edn. PO Box 987, Crows Nest, Sydney NSW 2065, Australia, 1990.

    Google Scholar 

  9. Moreau P, Milpied N, Mahe B et al. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant 1999; 23: 1003–1006.

    Article  CAS  PubMed  Google Scholar 

  10. Yuhas JM . Differential protection of normal and malignant tissues against the cytotoxic effects of mechlorethamine. Cancer Treat Rep 1979; 63: 971–976.

    CAS  PubMed  Google Scholar 

  11. Yuhas JM, Spellman JM, Culo F . The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin Trials 1980; 3: 211–216.

    CAS  PubMed  Google Scholar 

  12. Yuhas JM, Spellman JM, Jordan SW et al. Treatment of tumours with the combination of WR-2721 and cis-dichlorodiammineplatinum (II) or cyclophosphamide. Br J Cancer 1980; 42: 574–585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yuhas JM . Active vs passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res 1980; 40: 1519–1524.

    CAS  PubMed  Google Scholar 

  14. Millar JL, McElwain TJ, Clutterbuck RD et al. The modification of melphalan toxicity in tumor bearing mice by s-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR 2721). Am J Clin Oncol 1982; 5: 321–328.

    Article  CAS  PubMed  Google Scholar 

  15. Turrisi AT, Glover DJ, Hurwitz S et al. Final report of the phase I trial of single-dose WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]. Cancer Treat Rep 1986; 70: 1389–1393.

    CAS  PubMed  Google Scholar 

  16. Kemp G, Rose P, Lurain J et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996; 14: 2101–2112.

    Article  CAS  PubMed  Google Scholar 

  17. De Souza CA, Santini G, Marino G et al. Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study. Brazil J Med Biol Res 2000; 33: 791–798.

    Article  CAS  Google Scholar 

  18. Yuhas JM, Storer JB . Differential chemoprotection of normal and malignant tissues. J Natl Cancer Inst 1969; 42: 331–335.

    CAS  PubMed  Google Scholar 

  19. Grdina DJ, Sigdestad CP . Radiation protectors: the unexpected benefits. Drug Metab Rev 1989; 20: 13–42.

    Article  CAS  PubMed  Google Scholar 

  20. Hartmann JT, von Vangerow A, Fels LM et al. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. Br J Cancer 2001; 84: 313–320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Capelli D, Santini G, De Souza C et al. Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cell autotransplant: a retrospective study. Br J Haematol 2000; 110: 300–307.

    Article  CAS  PubMed  Google Scholar 

  22. Jantunen E, Kuittinen T, Nousiainen T . A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients. Leukemia Lymphoma 2002; 43: 1961–1965.

    Article  CAS  PubMed  Google Scholar 

  23. Thieblemont C, Dumontet C, Saad H et al. Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 2002; 30: 769–775.

    Article  CAS  PubMed  Google Scholar 

  24. Phillips Jr GL . The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Semin Oncol 2002; 29: 53–56.

    Article  CAS  PubMed  Google Scholar 

  25. Schuchter LM . Guidelines for the administration of amifostine. Semin Oncol 1996; 23: 40–43.

    CAS  PubMed  Google Scholar 

  26. Miller AB, Hoogstraten B, Staquet M et al. Reporting results of cancer treatment. Cancer 1981; 47: 207–214.

    Article  CAS  PubMed  Google Scholar 

  27. Gore ME, Selby PJ, Viner C et al. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet 1989; II: 879–881.

    Article  Google Scholar 

  28. Blade J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  29. Barlogie B, Jagannath S, Desikan KR et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65.

    CAS  PubMed  Google Scholar 

  30. Desikan R, Barlogie B, Sawyer J et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95: 4008–4010.

    CAS  PubMed  Google Scholar 

  31. Betticher DC, Anderson H, Ranson M et al. Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small cell lung cancer: a randomised Phase II study. Br J Cancer 1995; 72: 1551–1555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Budd GT, Ganapathi R, Adelstein DJ et al. Randomized trial of carboplatin plus amifostine vs carboplatin alone in patients with advanced solid tumors. Cancer 1997; 80: 1134–1140.

    Article  CAS  PubMed  Google Scholar 

  33. Douay L, Hu C, Giarratana MC et al. Amifostine (WR-2721) protects normal haematopoietic stem cells against cyclophosphamide derivatives' toxicity without compromising their antileukaemic effects. Eur J Cancer 1995; 31A: S14–S16.

    Article  CAS  PubMed  Google Scholar 

  34. Buschini A, Anceschi E, Carlo-Stella C et al. Amifostine (WR-2721) selective protection against melphalan genotoxicity. Leukemia 2000; 14: 1642–1651.

    Article  CAS  PubMed  Google Scholar 

  35. Shpall EJ, Stemmer SM, Hami L et al. Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support. Blood 1994; 83: 3132–3137.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported in part by Schering Plough, who also provided the amifostine, and in part by Amgen Australia. AS is supported by The Anderson Trust.

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Authors and Affiliations

  1. Clinical Haematology & BMT, The Alfred Hospital, Melbourne, Australia

    A Spencer

  2. Division of Haematology, Institute of Medical & Veterinary Science, Adelaide, Australia

    N Horvath

  3. Haematology Department, Royal Prince Alfred Hospital, Camperdown, Australia

    J Gibson

  4. Haematology Service, Peter MacCallum Cancer Centre, Melbourne, Australia

    H M Prince

  5. Department of Haematology, Royal Perth Hospital, Perth, Australia

    R Herrmann

  6. Wesley Medical Centre, Auchenflower, Australia

    J Bashford

  7. Haematology Clinics, Sir Charles Gardiner Hospital, Nedlands, Australia

    D Joske

  8. BMT Service, Royal Melbourne Hospital, Parkville, Australia

    A Grigg

  9. Department of Oncology, Box Hill Hospital, Box Hill, Australia

    J McKendrick

  10. Haematology Department, The Canberra Hospital, Woden, Australia

    I Prosser

  11. Clinical Haematology & Medical Oncology Unit, Royal Hobart Hospital, Hobart, Australia

    R Lowenthal

  12. Hunter Haematology Unit, Newcastle Mater Misericordiae Hospital, Newcastle, Australia

    S Deveridge

  13. Department of Haematology, Mater Hospital, Brisbane, Australia

    K Taylor

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on behalf of The Australasian Leukaemia and Lymphoma Group

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Correspondence to A Spencer.

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Spencer, A., Horvath, N., Gibson, J. et al. Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant 35, 971–977 (2005). https://doi.org/10.1038/sj.bmt.1704946

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