A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial
Open Access
- 12 August 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 26 (2), 349-355
- https://doi.org/10.1038/leu.2011.204
Abstract
The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.Keywords
This publication has 33 references indexed in Scilit:
- First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trialThe Lancet, 2010
- Superior results of Total Therapy 3 (2003-33) in gene expression profiling–defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenanceBlood, 2010
- The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significanceHaematologica, 2010
- Homozygous Deletion Mapping in Myeloma Samples Identifies Genes and an Expression Signature Relevant to Pathogenesis and OutcomeClinical Cancer Research, 2010
- Combining information regarding chromosomal aberrations t(4;14) and del(17p13) with the International Staging System classification allows stratification of myeloma patients undergoing autologous stem cell transplantationHaematologica, 2010
- International Myeloma Working Group molecular classification of multiple myeloma: spotlight reviewLeukemia, 2009
- Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple MyelomaNew England Journal of Medicine, 2008
- Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2British Journal of Haematology, 2008
- The molecular classification of multiple myelomaBlood, 2006
- Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantationBlood, 2006