Blood Journal
Leading the way in experimental and clinical research in hematology

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome

  1. Hervé Avet-Loiseau1,2,
  2. Michel Attal3,
  3. Philippe Moreau1,4,
  4. Catherine Charbonnel1,2,
  5. Frédéric Garban5,
  6. Cyrille Hulin6,
  7. Serge Leyvraz7,
  8. Mauricette Michallet8,
  9. Ibrahim Yakoub-Agha9,
  10. Laurent Garderet10,
  11. Gérald Marit11,
  12. Lucienne Michaux12,
  13. Laurent Voillat13,
  14. Marc Renaud14,
  15. Bernard Grosbois15,
  16. Gaelle Guillerm16,
  17. Lotfi Benboubker17,
  18. Mathieu Monconduit18,
  19. Catherine Thieblemont19,
  20. Philippe Casassus20,
  21. Denis Caillot21,
  22. Anne-Marie Stoppa22,
  23. Jean-Jacques Sotto5,
  24. Marc Wetterwald23,
  25. Charles Dumontet8,
  26. Jean-Gabriel Fuzibet24,
  27. Isabelle Azais25,
  28. Véronique Dorvaux26,
  29. Marc Zandecki27,
  30. Régis Bataille1,
  31. Stéphane Minvielle1,2,
  32. Jean-Luc Harousseau4,
  33. Thierry Facon9, and
  34. Claire Mathiot28
  1. 1Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 601, Nantes, France;
  2. 2Hematology Laboratory, University Hospital Hôtel-Dieu, Nantes, France;
  3. 3Hematology Department, University Hospital Purpan, Toulouse, France;
  4. 4Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
  5. 5Hematology Department, University Hospital Michalon, Grenoble, France;
  6. 6Hematology Department, University Hospital Brabois, Nancy, France;
  7. 7Hematology Department, University Hospital, Lausanne, Switzerland, for the Swiss Group for Clinical Cancer Research (SAKK);
  8. 8Hematology Department, University Hospital Edouard Herriot, Lyon, France;
  9. 9Hematology Department, University Hospital Huriez, Lille, France;
  10. 10Hematology Department, University Hospital Saint-Antoine, Paris, France;
  11. 11Hematology Department, University Hospital Haut-Lévêque, Bordeaux, France;
  12. 12Hematology Department, University Hospital, Haine, Belgium;
  13. 13Hematology Department, University Hospital Minjoz, Besançon, France;
  14. 14Hematology Department, University Hospital Jean Bernard, Poitiers, France;
  15. 15Internal Medicine Department, University Hospital Sud, Rennes, France;
  16. 16Hematology Department, University Hospital Morvan, Brest, France;
  17. 17Hematology Department, University Hospital Bretonneau, Tours, France;
  18. 18Hematology Department, Becquerel Cancer Center, Rouen, France;
  19. 19Hematology Department, University Hospital, Pierre-Bénite, France;
  20. 20Hematology Department, University Hospital Avicenne, Bobigny, France;
  21. 21Hematology Department, University Hospital, Dijon, France;
  22. 22Hematology Department, Paoli Calmette Cancer Center, Marseille, France;
  23. 23Hematology Department, Hospital, Dunkerque, France;
  24. 24Internal Medicine Department, University Hospital L'Archet 1, Nice, France;
  25. 25Rheumatology Department, University Hospital Jean Bernard, Poitiers, France;
  26. 26Hematology Department, Hospital Nôtre-Dame de Bon Secours, Metz, France;
  27. 27Hematology Laboratory, University Hospital Larrey, Angers, France;
  28. 28Hematology Department, Curie Cancer Center, Paris, France

Abstract

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

  • Submitted August 15, 2006.
  • Accepted September 21, 2006.
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