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Combining chromosomal aberrations t(4;14) and del(17p13) with ISS allows a stratification of myeloma patients undergoing autologous stem cell transplantation

¹ Medizinische Klinik V, Universitätsklinikum, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
² Institut für Humangenetik, Universitätsklinikum, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
³ Abteilung für Biostatistik, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
⁴ Nationales Centrum für Tumorerkrankungen, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany

Correspondence: Kai Neben, M.D., Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; Phone: international +49.6221568001. Fax: international +49.6221565721. E-mail: kai.neben{at}med.uni-heidelberg.de

ABSTRACT

Background: Chromosomal abnormalities have been shown to play a major role in disease evolution of multiple myeloma (MM). By using fluorescent in situ hybridization (FISH), specific changes in interphase cells can be detected, overcoming the problem of the lack of dividing cells required for conventional cytogenetics.

Design and Methods: We analyzed the prognostic value of 12 frequent chromosomal abnormalities by FISH in a series of patients (n=315) with newly diagnosed symptomatic MM as presenting in our center. All patients underwent frontline autologous stem cell transplantation (ASCT) according or in analogy to the GMMG-HD3- or GMMG-HD4-trials.

Results: Univariate statistical analyses revealed that the presence of del(13q14), del(17p13), t(4;14), +1q21 and nonhyperdiploidy was associated with an adverse progression-free (PFS) and overall survival (OS) independent of the international staging system (ISS). Multivariate analyses showed that only t(4;14) and del(17p13) retained prognostic value for both PFS and OS. The combination of t(4;14) and del(17p13) with the ISS allowed a stratification of patients into three distinct groups: favourable prognosis (absence of t(4;14)/del(17p13) and ISS I), poor prognosis (presence of t(4;14)/del(17p13) and ISS II/III) and intermediate prognosis (all remaining patients). The probabilities for OS at 5-years decreased from 72% in the favourable prognostic group to 62% (Hazard Ratio 2.4; p=0.01) in the intermediate and 41% (Hazard Ratio 5.6; p<0.001) in the poor prognostic group, respectively.

Conclusions: These results have implications for the risk-adapted management for MM patients undergoing high-dose chemotherapy followed by ASCT and suggest that new treatment concepts are urgently needed for patients who belong to the poor prognosis group. As targeted therapies evolve, different treatment options might have variable success, depending on the underlying genetic nature of the clone.