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Myeloma

Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m2)

Leukemia volume 18, pages 133–138 (2004)Cite this article

Abstract

Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) vs standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) is also superior to the standard dose, but has not been clinically compared with MEL200. A total of 90 patients at diagnosis were treated with two MEL100 courses. Their clinical outcome was compared with that of a control group of 90 pair mates matched for serum β2-microglobulin levels and Durie and Salmon clinical stage. These patients were treated at diagnosis with two MEL200 courses. Patient characteristics were similar in both groups except that the median age of the MEL100 group was significantly higher (P<0.0001). Complete remission was 35% after MEL100 and 48% after MEL200 (P=0.08). Median event-free survival (EFS) was 32 months in the MEL100 group and 42 months in the MEL200 group (P<0.005), but overall survival (OS) was not different. Transplant-related mortality was not significantly different. Haematological and extra-haematological toxicity was significantly reduced after MEL100. Despite the significant age difference, tandem MEL100 was less toxic than tandem MEL200, and MEL100 was inferior to MEL200 in terms of EFS but not in terms of OS. The intensified nonmyeloablative MEL100 regimen is an effective first-line treatment.

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References

  1. Alegre A, Dìaz-Mediavilla J, San Miguel J, Martinez R, Garcia Larana J, Sureda A et al. Autologous peripheral blood stem cell transplantation for multiple myeloma: a report of 259 cases from the Spanish Registry. Bone Marrow Transplant 1998; 21: 133–140.

    Article  CAS  PubMed  Google Scholar 

  2. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  3. Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789–793.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  5. Bjorkstrand B, Ljungman P, Svensson H, Hermans J, Alegre A, Apperley J et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 1996; 88: 4711–4718.

    CAS  PubMed  Google Scholar 

  6. Gianni AM, Tarella C, Bregni M, Siena S, Lombardi F, Gandola L et al. High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma. J Clin Oncol 1994; 12: 503–509.

    Article  CAS  PubMed  Google Scholar 

  7. Lenhoff S, Hjorth M, Holmberg E, Turesson I, Westin J, Nielsen JL et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly dignosed multiple myeloma: a population-based study. Blood 2000; 95: 7–11.

    CAS  PubMed  Google Scholar 

  8. Moreau P, Misbahi R, Milpied N, Morineau N, Mahe B, Vigier M et al. Long-term results (12 years) of high-dose therapy in 127 patients with de novo multiple myeloma. Leukemia 2002; 16: 1838–1843.

    Article  CAS  PubMed  Google Scholar 

  9. Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Bracy D et al. Autotransplants in multiple myeloma: what have we learned? Blood 1996; 88: 838–847.

    CAS  PubMed  Google Scholar 

  10. Imrie K, Esmail R, Meyer RM . The role of high-dose chemotherapy and stem-cell transplantation in patients with multiple myeloma: a practice guideline of the Cancer Care Ontario Practice Guidelines Initiative. Ann Intern Med 2002; 136: 619–629.

    Article  PubMed  Google Scholar 

  11. Siegel D, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 1999; 93: 51–54.

    CAS  PubMed  Google Scholar 

  12. Avet-Loiseau H, Facon T, Grosbois B, Mangrageas F, Rapp MJ, Harousseau JL et al. Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation. Blood 2002; 99: 2185–2191.

    Article  CAS  PubMed  Google Scholar 

  13. Fassas A, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol 2002; 118: 1041–1047.

    Article  CAS  PubMed  Google Scholar 

  14. Nilsson T, Lenhoff S, Turesson I, Rylander L, Mitelman F, Westin J et al. Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation. Eur J Haematol 2002; 68: 345–353.

    Article  CAS  PubMed  Google Scholar 

  15. Palumbo A, Pileri A, Triolo S, Omede P, Bruno B, Ciravegna G et al. Multicyclic, dose-intensive chemotherapy supported by hemopoietic progenitors in refractory myeloma patients. Bone Marrow Transplant 1997; 19: 23–29.

    Article  CAS  PubMed  Google Scholar 

  16. Palumbo A, Triolo S, Argentino C, Bringhen S, Dominietto A, Rus C et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: 1248–1253.

    CAS  PubMed  Google Scholar 

  17. Durie BGM, Salmon SE . Multiple myeloma, macroglobulinemia and monoclonal gammopathies. In: Hoffbrand AV, Brown MC, Hirsch J (eds). Recent Advances in Haematology. Edinburgh: Churchill Livingstone, 1977, pp 243–261.

    Google Scholar 

  18. Durie BGM, Salmon SE . A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 1975; 36: 842–854.

    Article  CAS  PubMed  Google Scholar 

  19. Siena S, Bregni M, Brando B, Belli N, Ravagnani F, Gandola L et al. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood 1991; 77: 400–409.

    CAS  PubMed  Google Scholar 

  20. Corradini P, Voena C, Tarella C, Astolfi M, Ladetto M, Palumbo A et al. Molecular and clinical remission in multiple myeloma: the role of autologous and allogeneic transplantation of hematopoietic cells. J Clin Oncol 1999; 17: 208–215.

    Article  CAS  PubMed  Google Scholar 

  21. Tribalto M, Amadori S, Cudillo L, Caravita T, Del Poeta G, Meloni G et al. Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma : an Italian Multicenter Study. Haematologica 2000; 85: 52–58.

    CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  23. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Phil D et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. New Engl J Med 2003; 348: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  24. Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroup Francophone du myélome 9502 randomized trial. Blood 2002; 99: 731–735.

    Article  CAS  PubMed  Google Scholar 

  25. Gregory WM, Richards MA, Malpas JS . Combination chemotherapy versus melphalan and prednisone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 1992; 10: 334–342.

    Article  CAS  PubMed  Google Scholar 

  26. Segeren CM, Sonneveld P, van der Holt B, Vellenga E, Croockewit AJ, Verhoef GEG et al. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood 2003; 101: 2144–2151.

    Article  CAS  PubMed  Google Scholar 

  27. Ries L, Hankey BL, Miller BA . Cancer Statistic Review, 1973–1988 (DHHS publ-NIH-n.91-2789). Washington, DC: US Govt Printing Office, 1991.

  28. Sirohi B, Powles R, Treleaven J, Mainwaring P, Kulkarni S, Pandha H et al. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Blood 2000; 25: 533–539.

    CAS  Google Scholar 

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Acknowledgements

This work was supported in part by Associazione Italiana Ricerca Cancro (AIRC), Associazione Italiana Leucemie (AIL), Compagnia di San Paolo and Ministero Università e Ricerca Scientifica e Tecnologica (MURST). We thank Miss Tiziana Marangon for her technical assistance in the preparation of manuscipt. We also thank the many medical and nursing colleagues who have participated in the treatment of patients.

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Authors and Affiliations

  1. Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S Giovanni Battista, Torino, Italy

    A Palumbo, S Bringhen, A Bertola, F Cavallo, P Falco, M Massaia, B Bruno & M Boccadoro

  2. Laboratory of Onco-Hematology Research Center on Experimental Medicine, Torino, Italy

    M Massaia

  3. Ospedale Evangelico Valdese, Torino, Italy

    C Rus

  4. Divisione di Ematologia, Ospedali Riuniti, Bergamo, Italy

    A Barbui

  5. Cattedra di Ematologia, Policlinico S Eugenio, Roma, Italy

    T Caravita

  6. Dipartimento di Onco-Ematologia, IRCCS, Casa Sollievo della Sofferenza, S Giovanni Rotondo, Italy

    P Musto

  7. Ospedale Lorenz B:Ohler, Bolzano, Italy

    N Pescosta

  8. Ematologia, HS Gerardo, Monza, Italy

    F Rossini

  9. Cattedra di Ematologia, Università Cattolica S Cuore, Roma, Italy

    M Vignetti

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  1. A Palumbo
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Correspondence to M Boccadoro.

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Palumbo, A., Bringhen, S., Bertola, A. et al. Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m2). Leukemia 18, 133–138 (2004). https://doi.org/10.1038/sj.leu.2403196

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