A Comprehensive Analysis of Cytogenetic Abnormalities in Myeloma: Results of the FISH Analysis of 1000 Patients Enrolled in the IFM99 Trials

• Published in: Blood 2005-11, Vol.106 (11), p.622-622
• Main Authors: Loiseau, Herve Avet, Attal, Michel, Moreau, Philippe, Charbonnel, Catherine, Garban, Frederic, Harousseau, Jean-Luc, Facon, Thierry, Mathiot, Claire
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V106.11.622.622

Because cytogenetics has been demonstrated to be the most powerful prognostic factor in many hematopoietic malignancies, we hypothesized that chromosomal abnormalities may also predict outcome in MM, as previously suggested by several reports. In order to test this hypothesis, we analyzed the main chromosomal abnormalities in a large series of 1000 patients with newly diagnosed MM, enrolled in the IFM 99 therapeutic trial. This trial enrolled 1083 patients under the age of 65, between May 2000 and December 2003. Briefly, the patients were treated by an induction therapy (4 VAD courses), followed by 2 courses of high-dose melphalan. In patients with less than 2 poor-prognosis factors (del(13) and b2m>3), a maintenance therapy was randomized (none vs pamidronate vs pamidronate + thalidomide). For all the patients, a fresh bone marrow specimen was shipped overnight to the central laboratory in Nantes. After separation of the mononuclear cells, malignant plasma cells were sorted using magnetic beads coated with an anti-CD138 monoclonal antibody. All the analyzed specimens presented a plasma cell purity > 90%. The patients were then analyzed by FISH for the following abnormalities: del(13q14), t(4;14), t(11;14), del(17p13), MYC rearrangements, hyperdiploidy (assessed by interphase FISH as previously reported), and 1q21 gains (CKS1B). Abnormalities were observed in 45%, 14%, 21%, 11%, 13%, 40%, and 40%, respectively, in agreement with previously reported incidences. We then looked at the prognostic impact of these chromosomal abnormalities, analyzing both the overall survival (OS) and the event-free survival (EFS). With a median follow-up of 32 months, t(11;14) and MYC rearrangements were not significant for both OS and EFS, and hyperdiploidy was marginally significant (p=.03, and .02 for EFS and OS, respectively, with a longer survival for hyperdiploid patients). In contrast, del(13), t(4;14), del(17p) and 1q gains significantly negatively impacted both EFS and OS (p