Evidence for Cytogenetic and Fluorescence In Situ Hybridization Risk Stratification of Newly Diagnosed Multiple Myeloma in the Era of Novel Therapies

Kapoor, Prashant; Fonseca, Rafael; Rajkumar, S. Vincent; Sinha, Shirshendu; Gertz, Morie A.; Stewart, A. Keith; Bergsagel, P. Leif; Lacy, Martha Q.; Dingli, David D.; Ketterling, Rhett P.; Buadi, Francis; Kyle, Robert A.; Witzig, Thomas E.; Greipp, Philip R.; Dispenzieri, Angela; Kumar, Shaji
June 2010
Mayo Clinic Proceedings;Jun2010, Vol. 85 Issue 6, p532
Academic Journal
Overall survival (OS) has improved with increasing use of novel agents in multiple myeloma (MM). However, the disease course remains highly variable, and the heterogeneity largely reflects different genetic abnormalities. We studied the impact of the Mayo risk-stratification model of MM on patient outcome in the era of novel therapies, evaluating each individual component of the model-fluorescence in situ hybridization (FISH), conventional cytogenetics (CG), and the plasma cell labeling index-that segregates patients into high- and standard-risk categories. This report consists of 290 patients with newly diagnosed MM, predominantly treated with novel agents, who were risk-stratified at diagnosis and were followed up for OS. Of these patients, 81% had received primarily thalidomide (n=50), lenalidomide (n=199), or bortezomib (n=79) as frontline or salvage therapies. Our retrospective analysis validates the currently proposed Mayo risk-stratification model (median OS, 37 months vs not reached for high- and standard-risk patients, respectively; P=.003). Although the FISH or CG test identifies a high-risk cohort with hazard ratios of 2.1 (P=.006) and 2.5 (P=.006), respectively, the plasma cell labeling index cutoff of 3% fails to independently prognosticate patient risk (hazard ratio, 1.4; P=.41). In those stratified as standard-risk by one of the 2 tests (FISH or CG), the other test appears to be of additional prognostic significance. This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents.


Related Articles

  • The role of cytogenetics in myeloma. Zhan, F.; Sawyer, J.; Tricot, G. // Leukemia (08876924);Sep2006, Vol. 20 Issue 9, p1484 

    The article analyzes the role of cytogenetics in myeloma, in leukemia research. Multiple myeloma is a slow progressing disease caused by the death of mature B cells of bone marrow. Active stage is preceded by dormant phase. The different methods of treatment like deletion of chromozome 13,...

  • Cytogenetics of Multiple Myeloma. Trčić, Ružica Lasan; Skelin, Ika Kardum; Šušterčić, Dunja; Planinc-Peraica, Ana; Ajduković, Radmila; Hariš, Višnja; Kušec, Rajko; Begović, Davor // Collegium Antropologicum;Mar2010, Vol. 34 Issue 1, p41 

    Great studies of multiple myeloma (MM) strongly suggested that specific chromosomal changes are of prognostic significance in patients with MM¹. We have performed cytogenetic analysis and recently fluorescent in situ hybridization (FISH) on 43 cases of MM. Clonal chromosomal changes were...

  • Plasma Cell Specific Fluorescence in situ Hybridisation for Multiple Myeloma. Talley, Polly; Watmore, A. // Journal of Medical Genetics;Sep2003 Supplement, Vol. 40, pS56 

    Multiple Myeloma (MM) is a neoplastic proliferation of bone marrow plasma cells. Plasma cells, even in MM, can be present in relatively low numbers and divide infrequently. Consequently, conventional metaphase cytogenetic studies can be extremely difficult. Chromosome abnormalities are reported...

  • Novel deletion variants of 9q13–q21.12 and classical euchromatic variants of 9q12/qh involve deletion, duplication and triplication of large tracts of segmentally duplicated pericentromeric euchromatin. Willatt, Lionel R.; Barber, John C. K.; Clarkson, Amanda; Simonic, Ingrid; Raymond, F. Lucy; Docherty, Zoe; Ogilvie, Caroline Mackie // European Journal of Human Genetics;Jan2007, Vol. 15 Issue 1, p45 

    Large-scale copy number variation that is cytogenetically visible in normal individuals has been described as euchromatic variation but needs to be distinguished from pathogenic euchromatic deletion or duplication. Here, we report eight patients (three families and two individuals) with...

  • Retrospective analysis of genetic abnormalities and survival in 131 patients with multiple myeloma. NIAN LIU; HEBING ZHOU; GUANGZHONG YANG; CHUANYING GENG; YUAN JIAN; HUAN GUO; WENMING CHEN // Oncology Letters;2015, Vol. 9 Issue 2, p930 

    Genetic abnormalities in patients with multiple myeloma (MM) are important risk factors in terms of prognosis. In the present study, the prognostic value of several common MM genetic abnormalities was investigated. Interphase fluorescence in situ hybridization (iFISH) was used to detect genetic...

  • Fluorescence in situ hybridization analysis of chromosome aberrations in 60 Chinese patients with multiple myeloma. Gao, Xiao; Li, Chunming; Zhang, Run; Yang, Ruifang; Qu, Xiaoyan; Qiu, Hairong; Xu, Jiaren; Lu, Hua; Li, Jianyong; Chen, Lijuan // Medical Oncology;Sep2012, Vol. 29 Issue 3, p2200 

    Conventional cytogenetic analysis is often hampered owing to the low mitotic index of multiple myeloma (MM) cells in bone marrow samples of MM. Interphase fluorescence in situ hybridization (I-FISH) analysis combined with magnetic-activated cell sorting (MACS) has substantially enhanced the...

  • MALT Lymphoma Involving the Kidney: A Report of 10 Cases and Review of the Literature. Mar Garcia; Sergej Konoplev; Cristian Morosan; Lynne Abruzzo; Carlos Bueso-Ramos; L. Medeiros // American Journal of Clinical Pathology;Sep2007, Vol. 128 Issue 3, p464 

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) can arise at any anatomic site, but involvement of the kidney is rare. We describe 10 cases of kidney MALT lymphoma, including 6 localized cases. No predisposing inflammatory conditions were identified,...

  • MOVING BEYOND THE MICROSCOPE.  // Dog Watch;Aug2014, Vol. 18 Issue 8, p4 

    The article offers information on the fluorescence in situ hybridization (FISH) technique used by Simpson Laboratory to help understand and identify the role bacteria plays in various inflammatory bowel diseases that hinges on an integrated approach combining traditional and contemporary methods.

  • Multicolor-FISH Approaches for the Characterization of Human Chromosomes in Clinical Genetics and Tumor Cytogenetics. Liehr, Thomas; Claussen, Uwe // Current Genomics;Jun2002, Vol. 3 Issue 3, p213 

    A variety of multicolor fluorescence in situ hybridization (FISH) assays have been developed in the last decade. Routine application of such techniques started in 1996 with the simultaneous use of all the 24 human whole chromosome painting probes (i.e. multiplex-FISH = M-FISH and spectral...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics