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• W2013123944 abstract "Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000. Although no cure exists, many effective treatments are available that prolong survival and improve the quality of life of patients with this disease. The purpose of this consensus is to offer a simplified, evidence-based algorithm of decision making for patients with newly diagnosed myeloma. In cases in which evidence is lacking, our team of 18 Mayo Clinic myeloma experts reached a consensus on what therapy could generally be recommended. The focal point of our strategy revolves around risk stratification. Although a multitude of risk factors have been identified throughout the years, including age, tumor burden, renal function, lactate dehydrogenase, β2-microglobulin, and serum albumin, our group has now recognized and endorsed a genetic stratification and patient functional status for treatment. Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000. Although no cure exists, many effective treatments are available that prolong survival and improve the quality of life of patients with this disease. The purpose of this consensus is to offer a simplified, evidence-based algorithm of decision making for patients with newly diagnosed myeloma. In cases in which evidence is lacking, our team of 18 Mayo Clinic myeloma experts reached a consensus on what therapy could generally be recommended. The focal point of our strategy revolves around risk stratification. Although a multitude of risk factors have been identified throughout the years, including age, tumor burden, renal function, lactate dehydrogenase, β2-microglobulin, and serum albumin, our group has now recognized and endorsed a genetic stratification and patient functional status for treatment. Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000.1Jemal A Siegel R Ward E et al.Cancer statistics, 2006.CA Cancer J Clin. 2006; 56: 106-130Crossref PubMed Scopus (4107) Google Scholar Survival of patients with multiple myeloma varies from months to decades.2Kyle RA Long-term survival in multiple myeloma.N Engl J Med. 1983; 308: 314-316Crossref PubMed Google Scholar, 3Long-term survival in multiple myeloma: a Finnish Leukaemia Group study.Br J Haematol. 1999; 105: 942-947Crossref PubMed Scopus (10) Google Scholar Historically, no precise methods have been available to identify the subset of patients with newly diagnosed myeloma who are best served by standard intensity therapies, maintenance therapies, novel therapies, or more intensive regimens. Although the Durie-Salmon system has separated patients predominantly by tumor burden and renal function,4Durie BG Salmon SE A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival.Cancer. 1975; 36: 842-854Crossref PubMed Google Scholar it has been supplanted by the International Staging System (ISS).5Greipp PR San Miguel J Durie BG et al.International staging system for multiple myeloma [published correction appears in J Clin Oncol. 2005 Sep 1;23:6281].J Clin Oncol. 2005 May 20; 23 (Epub 2005 Apr 4.): 3412-3420Crossref PubMed Scopus (787) Google Scholar The ISS incorporates the more easily reproducible parameters of albumin and β2-microglobulin, resulting in low-, intermediate-, and high-risk groups of patients with median overall survival (OS) times of 62, 45, and 29 months, respectively. Although the ISS is highly prognostic and important for comparing results across trials and providing a global estimate of outcome, for therapeutic purposes we favor a cytogenetics and proliferation-based model,6Stewart AK Bergsagel PL Greipp PR et al.A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy.Leukemia. 2007 Jan 18; ([Epub ahead of print])Google Scholar which appears to offer greater power and predictive value for risk stratification (Table 1).7Smadja NV Bastard C Brigaudeau C Leroux D Fruchart C Groupe Francais de Cytogenetique Hematologique Hypodiploidy is a major prognostic factor in multiple myeloma.Blood. 2001; 98: 2229-2238Crossref PubMed Scopus (209) Google Scholar, 8Fonseca R Blood E Rue M et al.Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood. 2003 Jun 1; 101 (Epub 2003 Feb 6.): 4569-4575Crossref PubMed Scopus (294) Google Scholar, 9Konigsberg R Zojer N Ackermann J et al.Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.J Clin Oncol. 2000; 18: 804-812PubMed Google Scholar, 10Tricot G Barlogie B Jagannath S et al.Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.Blood. 1995; 86: 4250-4256PubMed Google Scholar, 11Facon T Avet-Loiseau H Guillerm G Intergroupe Francophone du Myelome et al.Chromosome 13 abnormalities identified by FISH analysis and serum b2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy.Blood. 2001; 97: 1566-1571Crossref PubMed Scopus (263) Google Scholar, 12Fassas AB Spencer T Sawyer J et al.Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma.Br J Haematol. 2002; 118: 1041-1047Crossref PubMed Scopus (105) Google Scholar, 13Chiecchio L Protheroe RK Ibrahim AH et al.Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.Leukemia. 2006 Sep; 20 (Epub 2006 Jul 6.): 1610-1617Crossref PubMed Scopus (73) Google ScholarTABLE 1Genetic-Based Prognostic and Staging Systems in Patients With Newly Diagnosed Multiple Myeloma*Prognostic categories were defined based on patients treated with standard-intensity chemotherapy unless stated otherwise. β2M = β2-microglobulin; F-Δ = fluorescence in situ hybridization deletion; poor IgHt = poor prognosis IgH translocation; M-Δ = metaphase cytogenetic deletion; NR = not reached.ReferenceNo. of patientsRisk or stagePatients (%)FeaturesMedian overall survival (mo)Smadja et al,7Smadja NV Bastard C Brigaudeau C Leroux D Fruchart C Groupe Francais de Cytogenetique Hematologique Hypodiploidy is a major prognostic factor in multiple myeloma.Blood. 2001; 98: 2229-2238Crossref PubMed Scopus (209) Google Scholar 2001†Patients received either standard chemotherapy or high-dose chemotherapy with transplantation.159Low35β2M ≤3 mg/L and nonhypodiploid‡Metaphase cytogenetics.52Intermediate42β2M >3 mg/L or hypodiploid‡Metaphase cytogenetics.30High23β2M >3 mg/L and hypodiploid‡Metaphase cytogenetics.11Fonseca et al,8Fonseca R Blood E Rue M et al.Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood. 2003 Jun 1; 101 (Epub 2003 Feb 6.): 4569-4575Crossref PubMed Scopus (294) Google Scholar 2003275Low39Absence of F-Δ13q, t(4;14), t(14;16), and F-Δ 17p1350Intermediate37F-Δ13q42High24t(4;14), t(14;16), or Δ17pl325Konigsberg et al,9Konigsberg R Zojer N Ackermann J et al.Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.J Clin Oncol. 2000; 18: 804-812PubMed Google Scholar 200088Low36No F-Δ13q and β2 M ≤4 mg/L102Intermediate40F-Δ13q or β2M >4 mg/L46High24F-Δ13q and β2M >4 mg/L11Tricot et al,10Tricot G Barlogie B Jagannath S et al.Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.Blood. 1995; 86: 4250-4256PubMed Google Scholar 1995§Tandem transplantation study.147Low79Absence of M-Δ13q, and M-Δ11q>48Intermediate18M-Δ13q OR M-Δl lq>50High3M-Δ13q AND M-Δ11q12Facon et al,11Facon T Avet-Loiseau H Guillerm G Intergroupe Francophone du Myelome et al.Chromosome 13 abnormalities identified by FISH analysis and serum b2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy.Blood. 2001; 97: 1566-1571Crossref PubMed Scopus (263) Google Scholar 2001‖High-dose melphalan, single transplantation, or tandem transplantation.110Low20No F-Δ13q and β2M <2.5 mg/L>111Intermediate50F-Δ13q or β2M ≥2.5 mg/L47High30F-Δ13q and β2 M ≥2.5 mg/L25Fassas et al,12Fassas AB Spencer T Sawyer J et al.Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma.Br J Haematol. 2002; 118: 1041-1047Crossref PubMed Scopus (105) Google Scholar 2002§Tandem transplantation study.1475Low67No karyotypic abnormality51Intermediate16Not hypodiploid but karyotypic abnormality other than M-Δ13q36High17Hypodiploid or M-Δ13q19Chiecchio et al,13Chiecchio L Protheroe RK Ibrahim AH et al.Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.Leukemia. 2006 Sep; 20 (Epub 2006 Jul 6.): 1610-1617Crossref PubMed Scopus (73) Google Scholar 2006†Patients received either standard chemotherapy or high-dose chemotherapy with transplantation.470Low53No F-Δ13qNRIntermediate26F-Δ13q only29High18F-Δ13q + poor IgHt OR F-Δp5320Very high3F-Δ13q + poor IgHt AND F-Δp5313* Prognostic categories were defined based on patients treated with standard-intensity chemotherapy unless stated otherwise. β2M = β2-microglobulin; F-Δ = fluorescence in situ hybridization deletion; poor IgHt = poor prognosis IgH translocation; M-Δ = metaphase cytogenetic deletion; NR = not reached.† Patients received either standard chemotherapy or high-dose chemotherapy with transplantation.‡ Metaphase cytogenetics.§ Tandem transplantation study.‖ High-dose melphalan, single transplantation, or tandem transplantation. Open table in a new tab Several molecular classification systems have been proposed on the basis of gene expression profiling.14Agnelli L Bicciato S Mattioli M et al.Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations.J Clin Oncol. 2005 Oct 10; 23 (Epub 2005 Aug 29.): 7296-7306Crossref PubMed Scopus (66) Google Scholar, 15Bergsagel PL Kuehl WM Molecular pathogenesis and a consequent classification of multiple myeloma.J Clin Oncol. 2005; 23: 6333-6338Crossref PubMed Scopus (226) Google Scholar, 16Zhan F Huang Y Colla S et al.The molecular classification of multiple myeloma.Blood. 2006 Sep 15; 108 (Epub 2006 May 25.): 2020-2028Crossref PubMed Scopus (314) Google Scholar, 17Fonseca R Harrington D Blood E ECOG Myeloma Group et al.A molecular classification of multiple myeloma (MM), based on cytogenetic abnormalities detected by interphase FISH, is powerful in identifying discrete groups of patients with dissimilar prognosis [abstract].Blood. 2001; 98: 733a-734aCrossref Scopus (65) Google Scholar Although these systems may ultimately elucidate the pathogenesis of myeloma, they are not easily translated into routine clinical practice. In contrast, cytogenetic classification systems are readily applied in the clinic. Nearly all patients with myeloma have abnormal chromosomes by fluorescence in situ hybridization (FISH), including deletions, aneuploidy, and translocations,18Drach J Angerler J Schuster J et al.Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance.Blood. 1995; 86: 3915-3921PubMed Google Scholar, 19Zandecki M Lai JL Facon T Multiple myeloma: almost all patients are cytogenetically abnormal.Br J Haematol. 1996; 94: 217-227Crossref PubMed Google Scholar although abnormal karyotypes are seen in only 18% to 30% of cases using standard metaphase analysis.20Dao DD Sawyer JR Epstein J Hoover RG Barlogie B Tricot G Deletion of the retinoblastoma gene in multiple myeloma.Leukemia. 1994; 8: 1280-1284PubMed Google Scholar This apparent discrepancy is explained by the generally low proliferative rate of myeloma cells and the requirement of obtaining plasma cells (and not just the rapidly dividing normal myeloid precursors) in metaphase to generate informative conventional cytogenetics.21Dewald GW Kyle RA Hicks GA Greipp PR The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.Blood. 1985; 66: 380-390PubMed Google Scholar, 22Sawyer JR Waldron JA Jagannath S Barlogie B Cytogenetic findings in 200 patients with multiple myeloma.Cancer Genet Cytogenet. 1995; 82: 41-49Abstract Full Text PDF PubMed Scopus (253) Google Scholar, 23Smadja NV Fruchart C Isnard F et al.Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.Leukemia. 1998; 12: 960-969Crossref PubMed Google Scholar Therefore,any abnormality in conventional cytogenetics identifies a group with a higher proliferative rate24Rajkumar S Fonseca R Lacy M et al.Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma.Bone Marrow Transplant. 1999; 24: 497-503Crossref PubMed Google Scholar and a particularly poor prognosis. There is excellent correlation between abnormal conventional cytogenetics and a high plasma cell proliferative rate.25Rajkumar SV Fonseca R Dewald GW et al.Cytogenetic abnormalities correlate with the plasma cell labeling index and extent of bone marrow involvement in myeloma.Cancer Genet Cytogenet. 1999; 113: 73-77Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 26Zojer N Konigsberg R Ackermann J et al.Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.Blood. 2000; 95: 1925-1930PubMed Google Scholar Fonseca et al8Fonseca R Blood E Rue M et al.Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood. 2003 Jun 1; 101 (Epub 2003 Feb 6.): 4569-4575Crossref PubMed Scopus (294) Google Scholar have demonstrated that 3 distinct staging groups can be defined by the presence or absence of t(4;14)(p16.3;q32), t(14;16)(q32;q23), deletion 17p13, and deletion 13q by FISH (Table 1). Overall, nonhyperdiploid myeloma is associated with more aggressive disease except for t(11;14)(q13;q32) (Table 1). This association has been demonstrated by flow cytometric methods27Barlogie B Alexanian R Dixon D Smith L Smallwood L Delasalle K Prognostic implications of tumor cell DNA and RNA content in multiple myeloma.Blood. 1985; 66: 338-341PubMed Google Scholar, 28Morgan Jr, RJ Gonchoroff NJ Katzmann JA Witzig TE Kyle RA Greipp PR Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma.Am J Hematol. 1989; 30: 195-200Crossref PubMed Google Scholar, 29Chng WJ Ketterling RP Fonseca R Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma.Genes Chromosomes Cancer. 2006; 45: 1111-1120Crossref PubMed Scopus (17) Google Scholar and metaphase cytogenetics.7Smadja NV Bastard C Brigaudeau C Leroux D Fruchart C Groupe Francais de Cytogenetique Hematologique Hypodiploidy is a major prognostic factor in multiple myeloma.Blood. 2001; 98: 2229-2238Crossref PubMed Scopus (209) Google Scholar, 30Gould J Alexanian R Goodacre A Pathak S Hecht B Barlogie B Plasma cell karyotype in multiple myeloma.Blood. 1988; 71: 453-456PubMed Google Scholar, 31Seong C Delasalle K Hayes K et al.Prognostic value of cytogenetics in multiple myeloma.Br J Haematol. 1998; 101: 189-194Crossref PubMed Scopus (101) Google Scholar, 32Debes-Marun CS Dewald GW Bryant S et al.Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma.Leukemia. 2003; 17: 427-436Crossref PubMed Scopus (120) Google Scholar, 33Shaughnessy Jr, J Tian E Sawyer J et al.Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II.Br J Haematol. 2003; 120: 44-52Crossref PubMed Scopus (105) Google Scholar There are strong associations among nonhyperdiploid myeloma, deletions of chromosome 13, and immunoglobulin heavy chain translocations.34Fonseca R Debes-Marun CS Picken EB et al.The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.Blood. 2003 Oct 1; 102 (Epub 2003 Jun 12.): 2562-2567Crossref PubMed Scopus (131) Google Scholar In contrast, hyperdiploid myeloma, which is associated with good prognosis, is characterized by trisomies of chromosomes 3, 5, 6, 7, 9, 11, 15, 17, 19, and 21 by both metaphase cytogenetics22Sawyer JR Waldron JA Jagannath S Barlogie B Cytogenetic findings in 200 patients with multiple myeloma.Cancer Genet Cytogenet. 1995; 82: 41-49Abstract Full Text PDF PubMed Scopus (253) Google Scholar, 32Debes-Marun CS Dewald GW Bryant S et al.Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma.Leukemia. 2003; 17: 427-436Crossref PubMed Scopus (120) Google Scholar and FISH.35Garcia-Sanz R Orfao A Gonzalez M et al.Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics.Blood. 1999; 93: 1032-1037PubMed Google Scholar, 36Drach J Schuster J Nowotny H et al.Multiple myeloma: high incidence of chromosomal aneuploidy as detected by interphase fluorescence in situ hybridization.Cancer Res. 1995; 55: 3854-3859PubMed Google Scholar, 37Perez-Simon JA Garcia-Sanz R Tabernero MD et al.Prognostic value of numerical chromosome aberrations in multiple myeloma: a FISH analysis of 15 different chromosomes.Blood. 1998; 91: 3366-3371PubMed Google Scholar As indicated in Table 1, monoallelic loss of chromosome 13 (Δ13) or its long arm (Δ13q), when determined by metaphase cytogenetics, is a powerful adverse prognostic factor in patients treated with standard chemotherapy9Konigsberg R Zojer N Ackermann J et al.Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.J Clin Oncol. 2000; 18: 804-812PubMed Google Scholar, 38Fonseca R Harrington D Oken MM et al.Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an Eastern Cooperative Oncology Group study.Cancer Res. 2002; 62: 715-720PubMed Google Scholar, 39Chng WJ Santana-Davila R Van Wier SA et al.Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations.Leukemia. 2006; 20: 807-813Crossref PubMed Scopus (55) Google Scholar or high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT).10Tricot G Barlogie B Jagannath S et al.Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.Blood. 1995; 86: 4250-4256PubMed Google Scholar, 31Seong C Delasalle K Hayes K et al.Prognostic value of cytogenetics in multiple myeloma.Br J Haematol. 1998; 101: 189-194Crossref PubMed Scopus (101) Google Scholar, 40Tricot G Sawyer JR Jagannath S et al.Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants.J Clin Oncol. 1997; 15: 2659-2666Crossref PubMed Google Scholar, 41Desikan R Barlogie B Sawyer J et al.Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.Blood. 2000; 95: 4008-4010PubMed Google Scholar, 42Barlogie B Jagannath S Desikan KR et al.Total therapy with tandem transplants for newly diagnosed multiple myeloma.Blood. 1999; 93: 55-65PubMed Google Scholar Approximately 50% of patients newly diagnosed as having multiple myeloma have Δ13 or Δ13q by FISH (F-Δ13q).11Facon T Avet-Loiseau H Guillerm G Intergroupe Francophone du Myelome et al.Chromosome 13 abnormalities identified by FISH analysis and serum b2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy.Blood. 2001; 97: 1566-1571Crossref PubMed Scopus (263) Google Scholar, 26Zojer N Konigsberg R Ackermann J et al.Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.Blood. 2000; 95: 1925-1930PubMed Google Scholar, 38Fonseca R Harrington D Oken MM et al.Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an Eastern Cooperative Oncology Group study.Cancer Res. 2002; 62: 715-720PubMed Google Scholar, 43Fonseca R Oken MM Harrington D et al.Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy.Leukemia. 2001; 15: 981-986Crossref PubMed Scopus (74) Google Scholar Patients with F-Δ13q have a worse OS with standard chemotherapy,9Konigsberg R Zojer N Ackermann J et al.Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.J Clin Oncol. 2000; 18: 804-812PubMed Google Scholar, 26Zojer N Konigsberg R Ackermann J et al.Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.Blood. 2000; 95: 1925-1930PubMed Google Scholar, 38Fonseca R Harrington D Oken MM et al.Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an Eastern Cooperative Oncology Group study.Cancer Res. 2002; 62: 715-720PubMed Google Scholar high-dose therapy,11Facon T Avet-Loiseau H Guillerm G Intergroupe Francophone du Myelome et al.Chromosome 13 abnormalities identified by FISH analysis and serum b2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy.Blood. 2001; 97: 1566-1571Crossref PubMed Scopus (263) Google Scholar, 44Worel N Greinix H Ackermann J et al.Deletion of chromosome 13q14 detected by fluorescence in situ hybridization has prognostic impact on survival after high-dose therapy in patients with multiple myeloma.Ann Hematol. 2001; 80: 345-348Crossref PubMed Scopus (23) Google Scholar and interferon treatment.38Fonseca R Harrington D Oken MM et al.Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an Eastern Cooperative Oncology Group study.Cancer Res. 2002; 62: 715-720PubMed Google Scholar The negative prognostic effect of F-Δ13q is less than that for Δ13q by conventional cytogenetics (M-Δ13q), although it remains an independent prognostic factor. The poor prognosis associated with Δ13q may be because of other nonrandom, associated chromosomal abnormalities, such as immunoglobulin translocations and ploidy status.7Smadja NV Bastard C Brigaudeau C Leroux D Fruchart C Groupe Francais de Cytogenetique Hematologique Hypodiploidy is a major prognostic factor in multiple myeloma.Blood. 2001; 98: 2229-2238Crossref PubMed Scopus (209) Google Scholar, 34Fonseca R Debes-Marun CS Picken EB et al.The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.Blood. 2003 Oct 1; 102 (Epub 2003 Jun 12.): 2562-2567Crossref PubMed Scopus (131) Google Scholar, 39Chng WJ Santana-Davila R Van Wier SA et al.Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations.Leukemia. 2006; 20: 807-813Crossref PubMed Scopus (55) Google Scholar Up to 65% of patients with multiple myeloma have translocations that involve the heavy chain gene on chromosome 14. These translocations include illegitimate switch recombination of the variable regions of the immunoglobulin heavy chain gene at 14q32. Partners of the translocations into the immunoglobulin heavy chain switch region on chromosome 14 include chromosomes 11, 4, 6, and 16.45Chesi M Kuehl WM Bergsagel PL Recurrent immunoglobulin gene translocations identify distinct molecular subtypes of myeloma.Ann Oncol. 2000; 11: 131-135Abstract Full Text PDF PubMed Google Scholar The t(11;14)(q13;q32) translocation is the most common translocation in multiple myeloma, occurring in approximately 20% of patients.22Sawyer JR Waldron JA Jagannath S Barlogie B Cytogenetic findings in 200 patients with multiple myeloma.Cancer Genet Cytogenet. 1995; 82: 41-49Abstract Full Text PDF PubMed Scopus (253) Google Scholar, 34Fonseca R Debes-Marun CS Picken EB et al.The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.Blood. 2003 Oct 1; 102 (Epub 2003 Jun 12.): 2562-2567Crossref PubMed Scopus (131) Google Scholar, 46Fonseca R Blood EA Oken MM et al.Myeloma and the t(11;14)(q13;q32): evidence for a biologically defined unique subset of patients.Blood. 2002; 99: 3735-3741Crossref PubMed Scopus (139) Google Scholar Most publications suggest that this translocation and the related t(6;14)(p21;q32)47Shaughnessy Jr, J Gabrea A Qi Y et al.Cyclin D3 at 6p21 is dysregulated by recurrent chromosomal translocations to immunoglobulin loci in multiple myeloma.Blood. 2001; 98: 217-223Crossref PubMed Scopus (114) Google Scholar are associated with a favorable or neutral outcome in patients with multiple myeloma.9Konigsberg R Zojer N Ackermann J et al.Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.J Clin Oncol. 2000; 18: 804-812PubMed Google Scholar, 10Tricot G Barlogie B Jagannath S et al.Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.Blood. 1995; 86: 4250-4256PubMed Google Scholar In contrast, the t(4;14)(p16.3;q32) is present in 15% of patients,48Chesi M Nardini E Brents LA et al.Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.Nat Genet. 1997; 16: 260-264Crossref PubMed Scopus (413) Google Scholar, 49Chesi M Nardini E Lim RS Smith KD Kuehl WM Bergsagel PL The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.Blood. 1998; 92: 3025-3034Crossref PubMed Google Scholar, 50Richelda R Ronchetti D Baldini L et al.A novel chromosomal translocation t(4; 14)(p16.3;q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.Blood. 1997; 90: 4062-4070Crossref PubMed Google Scholar, 51Avet-Loiseau H Li JY Facon T et al.High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies.Cancer Res. 1998; 58: 5640-5645PubMed Google Scholar, 52Fonseca R Conte G Greipp PR Laboratory correlates in multiple myeloma: how useful for prognosis?.Blood Rev. 2001; 15: 97-102Abstract Full Text PDF PubMed Scopus (6) Google Scholar and t(14;16)(q32;q23) is present in approximately 5% of patients.34Fonseca R Debes-Marun CS Picken EB et al.The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.Blood. 2003 Oct 1; 102 (Epub 2003 Jun 12.): 2562-2567Crossref PubMed Scopus (131) Google Scholar, 49Chesi M Nardini E Lim RS Smith KD Kuehl WM Bergsagel PL The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.Blood. 1998; 92: 3025-3034Crossref PubMed Google Scholar Both convey a very poor prognosis (Table 1) and will be missed if FISH is not used to probe for their presence. The former translocation results in the up-regulation of fibroblast growth factor receptor 3 and in the hybrid transcript IgH/MMSET,48Chesi M Nardini E Brents LA et al.Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.Nat Genet. 1997; 16: 260-264Crossref PubMed Scopus (413) Google Scholar, 49Chesi M Nardini E Lim RS Smith KD Kuehl WM Bergsagel PL The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.Blood. 1998; 92: 3025-3034Crossref PubMed Google Scholar and the latter activates the c-maf proto-oncogene.49Chesi M Nardini E Lim RS Smith KD Kuehl WM Bergsagel PL The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.Blood. 1998; 92: 3025-3034Crossref PubMed Google Scholar Deletions of p53 (locus 17p13) as detected by FISH are present in 10% of patients with newly diagnosed myeloma8Fonseca R Blood E Rue M et al.Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood. 2003 Jun 1; 101 (Epub 2003 Feb 6.): 4569-4575Crossref PubMed Scopus (294) Google Scholar, 53Avet-Loiseau H Li JY Godon C et al.P53 deletion is not a frequent event in multiple myeloma.Br J Haematol. 1999; 106: 717-719Crossref PubMed Scopus (42) Google Scholar, 54Drach J Ackermann J Fritz E et al.Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy.Blood. 1998; 92: 802-809PubMed Google Scholar and confer a poorer survival.8Fonseca R Blood E Rue M et al.Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood. 2003 Jun 1; 101 (Epub 2003 Feb 6.): 4569-4575Crossref PubMed Scopus (294) Google Scholar, 54Drach J Ackermann J Fritz E et al.Presence of a p53 gene de" @default.
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• W2013123944 title "Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement" @default.
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