TY - JOUR
T1 - Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets
T2 - Superiority of molecular genetics
AU - Shaughnessy, John D.
AU - Haessler, Jeffrey
AU - Van Rhee, Frits
AU - Anaissie, Elias
AU - Pineda-Roman, Mauricio
AU - Cottler-Fox, Michele
AU - Hollmig, Klaus
AU - Zangari, Maurizio
AU - Mohiuddin, Abid
AU - Alsayed, Yazan
AU - Grazziutti, Monica
AU - Epstein, Joshua
AU - Crowley, John
AU - Barlogie, Bart
PY - 2007/6
Y1 - 2007/6
N2 - Prognostic models for multiple myeloma have been fraught with tremendous heterogeneity in outcome among subgroups. In the context of Total Therapy 2, a tandem transplant trial for newly diagnosed myeloma, comprehensive information was available in 220 patients on standard prognostic factors (SPF), magnetic resonance imaging (MRI)-defined focal lesions, cytogenetic abnormalities (CA), fluorescence-in-situ-hybridisation (FISH)-derived amplification of chromosome 1q21 (amp1q21) and deletion of 13q14, as well as gene expression profiling (GEP). Five multivariate analysis-based survival models were derived, utilising SPF only (model 1), with progressive addition of CA (model 2), MRI (model 3), FISH (model 4) and GEP (model 5). The R2 value, a measure of accounting for clinical outcome variability, increased progressively from 18% in model 1 to 38% in model 5. The hazard ratio for overall survival was highest for GEP (3.07, P < 0.001) followed by amp1q21 (1.71, P = 0.05). According to the presence of none (49%), one (35%) or both of these two risk features (16%), 3-year survival decreased progressively from 92% to 78% to 43% (P < 0.0001). Thus, the dominance over other prognostic parameters of molecular genetics justifies the generation of quantitative reverse transcription polymerase chain reaction methodology ('MM genetic kit') for the optimal risk stratification of patients participating in therapeutic trials.
AB - Prognostic models for multiple myeloma have been fraught with tremendous heterogeneity in outcome among subgroups. In the context of Total Therapy 2, a tandem transplant trial for newly diagnosed myeloma, comprehensive information was available in 220 patients on standard prognostic factors (SPF), magnetic resonance imaging (MRI)-defined focal lesions, cytogenetic abnormalities (CA), fluorescence-in-situ-hybridisation (FISH)-derived amplification of chromosome 1q21 (amp1q21) and deletion of 13q14, as well as gene expression profiling (GEP). Five multivariate analysis-based survival models were derived, utilising SPF only (model 1), with progressive addition of CA (model 2), MRI (model 3), FISH (model 4) and GEP (model 5). The R2 value, a measure of accounting for clinical outcome variability, increased progressively from 18% in model 1 to 38% in model 5. The hazard ratio for overall survival was highest for GEP (3.07, P < 0.001) followed by amp1q21 (1.71, P = 0.05). According to the presence of none (49%), one (35%) or both of these two risk features (16%), 3-year survival decreased progressively from 92% to 78% to 43% (P < 0.0001). Thus, the dominance over other prognostic parameters of molecular genetics justifies the generation of quantitative reverse transcription polymerase chain reaction methodology ('MM genetic kit') for the optimal risk stratification of patients participating in therapeutic trials.
KW - Gene expression profiling
KW - Molecular genetics
KW - Myeloma
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=34249275302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249275302&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2007.06586.x
DO - 10.1111/j.1365-2141.2007.06586.x
M3 - Article
C2 - 17489983
AN - SCOPUS:34249275302
SN - 0007-1048
VL - 137
SP - 530
EP - 536
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -