Risk stratification in multiple myeloma, part 1: Characterization of high-risk disease

Clinical Advances in Hematology and Oncology

Volumn 11, Issue 8, 2013, Pages 489-503

  Biran, Noa ^a   Jagannath, Sundar ^a   Chari, Ajai ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Cytogenetics; Fluorescence in situ hybridization; High risk; Multiple myeloma

Indexed keywords

BORTEZOMIB; CARFILZOMIB; CYCLIN D1; CYCLIN D3; DEXAMETHASONE; DOXORUBICIN; FIBROBLAST GROWTH FACTOR RECEPTOR 3; FLUORODEOXYGLUCOSE F 18; IMMUNOGLOBULIN; LACTATE DEHYDROGENASE; LENALIDOMIDE; MELPHALAN; POMALIDOMIDE; PREDNISONE; PROTEIN P53; SYNDECAN 1; THALIDOMIDE; TRANSCRIPTION FACTOR MAF; TRANSCRIPTION FACTOR MAFB; VINCRISTINE;

ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; CANCER STAGING; CLINICAL TRIAL (TOPIC); CYTOGENETICS; FLUORESCENCE IN SITU HYBRIDIZATION; GENE EXPRESSION; HUMAN; IMMUNOFLUORESCENCE TEST; KIDNEY FUNCTION; MULTIPLE MYELOMA; NUCLEAR MAGNETIC RESONANCE IMAGING; OVERALL SURVIVAL; PERFORMANCE; PHASE 3 CLINICAL TRIAL (TOPIC); PLASMA CELL LEUKEMIA; POSITRON EMISSION TOMOGRAPHY; RISK FACTOR;

DISEASE-FREE SURVIVAL; HUMANS; MULTIPLE MYELOMA; NEOPLASM STAGING; RISK FACTORS; SURVIVAL RATE;

EID: 84883395092     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (140)

1. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075-2085.
2. Nair B, van Rhee F, Shaughnessy JD Jr, et al. 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 maintenance. Blood. 2010;115(21):4168-4173.
3. Mateos MV, Oriol A, Martinez-Lopez J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010;11(10):934-941.
4. Boyd KD, Ross FM, Tapper WJ, et al. The clinical impact and molecular biology of del(17p) in multiple myeloma treated with conventional or thalidomide-based therapy. Genes Chromosomes Cancer. 2011;50(10):765-774.
5. Shaughnessy JD Jr, Zhan F, Burington BE, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276-2284.
6. Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood. 2013;121(6):884-892.
7. Durie 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(3):842-854.
8. Eleutherakis-Papaiakovou V, Bamias A, Gika D, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma. 2007;48(2):337-341.
9. Hari PN, Zhang MJ, Roy V, et al. Is the International Staging System superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant. Leukemia. 2009;23(8):1528-1534.
10. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-3420.
11. Cunningham D, Paz-Ares L, Milan S, et al. High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol. 1994;12(4):759-763.
12. Dimopoulos M, Terpos E, Comenzo RL, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia. 2009;23(9):1545-1556.
13. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011;117(18):4701-4705.
14. Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007;25(9):1121-1128.
15. Moulopoulos LA, Dimopoulos MA, Kastritis E, et al. Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: a single center experience on 228 patients. Am J Hematol. 2012;87(9):861-864.
16. Bartel TB, Haessler J, Brown TL, et al. F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood. 2009;114(10):2068-2076.
17. Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011;118(23):5989-5995.
18. Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695.
19. Usmani SZ, Heuck C, Mitchell A, et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012;97(11):1761-1767.
20. Tiedemann RE, Gonzalez-Paz N, Kyle RA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia. 2008;22(5):1044-1052.
21. Lopez-Anglada L, Gutierrez NC, Garcia JL, Mateos MV, Flores T, San Miguel JF. P53 deletion may drive the clinical evolution and treatment response in multiple myeloma. Eur J Haematol. 2010;84(4):359-361.
22. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121(5):749-757.
23. Blade J, Kyle RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol Oncol Clin North Am. 1999;13(6):1259-1272.
24. Chang H, Sloan S, Li D, Patterson B. Genomic aberrations in plasma cell leukemia shown by interphase fluorescence in situ hybridization. Cancer Genet Cytogenet. 2005;156(2):150-153.
25. Avet-Loiseau H, Roussel M, Campion L, et al. Cytogenetic and therapeutic characterization of primary plasma cell leukemia: the IFM experience. Leukemia. 2012;26(1):158-159.
26. Dimopoulos MA, Kastritis E, Delimpasi S, et al. Multiple myeloma in octogenarians: clinical features and outcome in the novel agent era. Eur J Haematol. 2012;89(1):10-15.
27. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol. 2000;65(3):175-181.
28. Siegel DS, Desikan KR, Mehta J, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood. 1999;93(1):51-54.
29. Myeloma survival statistics. Cancer Research UK website. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/myeloma/survival/multiplemyeloma-survival-statistics. Updated April 13, 2012. Accessed May 15, 2013.
30. Bringhen S, Mateos MV, Zweegman S, et al. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica. 2013;98(6):980-987.
31. Corrado C, Santarelli MT, Pavlovsky S, Pizzolato M. Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: A Grupo Argentino de Tratamiento de la Leucemia Aguda study. J Clin Oncol. 1989;7(12):1839-1844.
32. San Miguel JF, Sanchez J, Gonzalez M. Prognostic factors and classification in multiple myeloma. Br J Cancer. 1989;59(1):113-118.
33. Patel K, Orlowski R, Weber D, et al. Prognostic value of serum lactate dehydrogenase in symptomatic multiple myeloma. [ASCO abstract 8093]. J Clin Onc. 2012;30(15 suppl):8093.
34. Gkotzamanidou M, Kastritis E, Gavriatopoulou MR, et al. Increased serum lactate dehydrongenase should be included among the variables that define veryhigh-risk multiple myeloma. Clin Lymphoma Myeloma Leuk. 2011;11(5):409-413.
35. Terpos E, Katodritou E, Roussou M, et al. High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol. 2010;85(2):114-119.
36. Greipp PR, Lust JA, O'Fallon WM, Katzmann JA, Witzig TE, Kyle RA. Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. Blood. 1993;81(12):3382-3387.
37. Steensma DP, Gertz MA, Greipp PR, et al. A high bone marrow plasma cell labeling index in stable plateau-phase multiple myeloma is a marker for early disease progression and death. Blood. 2001;97(8):2522-2523.
38. Larsen JT, Chee CE, Lust JA, Greipp PR, Rajkumar SV. Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival. Blood. 2011;118(10):2702-2707.
39. Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012;12(5):335-348.
40. Munshi NC, Anderson KC, Bergsagel PL, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011;117(18):4696-4700.
41. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C; Groupe Français de Cytogénétique Hématologique. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98(7):2229-2238.
42. Debes-Marun CS, Dewald GW, Bryant S, et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia. 2003;17(2):427-436.
43. Rao PH, Cigudosa JC, Ning Y, et al. Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma. Blood. 1998;92(5):1743-1748.
44. Sawyer JR, Waldron JA, Jagannath S, Barlogie B. Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet. 1995;82(1):41-49.
45. Sawyer JR, Lukacs JL, Munshi N, et al. Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping. Blood. 1998;92(11):4269-4278.
46. Tonon G. Molecular pathogenesis of multiple myeloma. Hematol Oncol Clin North Am. 2007;21(6):985-1006.
47. Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002;2(3):175-187.
48. Lai YY, Huang XJ, Cai Z, et al. Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China. Chin Med J (Engl). 2012;125(15):2663-2670.
49. Dewald GW, Therneau T, Larson D, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood. 2005;106(10):3553-3558.
50. Takimoto M, Ogawa K, Kato Y, et al. Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF. Int J Hematol. 2008;87(3):260-265.
51. Chiecchio L, Protheroe RK, Ibrahim AH, et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia. 2006;20(9):1610-1617.
52. Stewart 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;21(3):529-534.
53. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64(4):1546-1558.
54. Magrangeas F, Lode L, Wuilleme S, Minvielle S, Avet-Loiseau H. Genetic heterogeneity in multiple myeloma. Leukemia. 2005;19(2):191-194.
55. Gutierrez NC, Castellanos MV, Martin ML, et al. Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia. 2007;21(1):143-150.
56. Drach 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(3):802-809.
57. Avet-Loiseau H, Li JY, Godon C, et al. P53 deletion is not a frequent event in multiple myeloma. Br J Haematol. 1999;106(3):717-719.
58. Chang H, Qi C, Yi QL, Reece D, Stewart AK. P53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood. 2005;105(1):358-360.
59. Chang H, Sloan S, Li D, et al. The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. Br J Haematol. 2004;125(1):64-68.
60. Gertz MA, Lacy MQ, Dispenzieri A, et al. Clinical implications of t(11;14) (q13;q32), t(4;14)(p16.3;q32), and-17p13 in myeloma patients treated with high-dose therapy. Blood. 2005;106(8):2837-2840.
61. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109(8):3489-3495.
62. Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene. 2001;20(40):5611-5622.
63. Zhan F, Hardin J, Kordsmeier B, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood. 2002;99(5):1745-1757.
64. Wu KL, Beverloo B, Lokhorst HM, et al. Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q deletions and are an adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. Br J Haematol. 2007;136(4):615-623.
65. Waheed S, Shaughnessy JD, van Rhee F, et al. International Staging System and metaphase cytogenetic abnormalities in the era of gene expression profiling data in multiple myeloma treated with Total Therapy 2 and 3 protocols. Cancer. 2011;117(5):1001-1009.
66. Qazilbash MH, Saliba RM, Ahmed B, et al. Deletion of the short arm of chromosome 1 (del 1p) is a strong predictor of poor outcome in myeloma patients undergoing an autotransplant. Biol Blood Marrow Transplant. 2007;13(9):1066-1072.
67. Kumar S, Fonseca R,KetterlingRP, et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood. 2012;119(9):2100-2105.
68. Avet-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(24):5640-5645.
69. Zhan F, Huang Y, Colla S, et al. The molecular classification of multiple myeloma. Blood. 2006;108(6):2020-2028.
70. Neben K, Jauch A, Bertsch U, et al. 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 transplantation. Haematologica. 2010;95(7):1150-1157.
71. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210-2221.
72. Shaughnessy JD Jr, Zhan F, Burington BE, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276-2284.
73. Moreau P, Attal M, Garban F, et al. Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials. Leukemia. 2007;21(9):2020-2024.
74. Mikhael JR, Dingli D, Roy V, et al. Management of newly diagnosed symptomatic multiple myeloma: Updated Mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360-376.
75. Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106(1):296-303.
76. Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101(11):4569-4575.
77. Boyd KD, Ross FM, Chiecchio L, et al. 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. Leukemia. 2012;26(2):349-355.
78. Avet-Loiseau H, Malard F, Campion L, et al. Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor? Blood. 2011;117(6):2009-2011.
79. Hurt EM, Wiestner A, Rosenwald A, et al. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell. 2004;5(2):191-199.
80. Chesi M, Kuehl WM, Bergsagel PL. Recurrent immunoglobulin gene translocations identify distinct molecular subtypes of myeloma. Ann Oncol. 2000;11(suppl 1):131-135.
81. Chang H, Ning Y, Qi X, Yeung J, Xu W. Chromosome 1p21 deletion is a novel prognostic marker in patients with multiple myeloma. Br J Haematol. 2007;139(1):51-54.
82. Hanamura I, Stewart JP, Huang Y, et al. 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 transplantation. Blood. 2006;108(5):1724-1732.
83. Grzasko N, Hus M, Pluta A, et al. Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients. Hematol Oncol. 2013;31(1): 41-48.
84. Nemec P, Zemanova Z, Greslikova H, et al. Gain of 1q21 is an unfavorable genetic prognostic factor for multiple myeloma patients treated with high-dose chemotherapy. Biol Blood Marrow Transplant. 2010;16(4):548-554.
85. Biran N, Najfeld V, Bagiella E, Jagannath S, Chari A. Patients with newly diagnosed multiple myeloma and a gain of the long arms of chromosome 1 have inferior outcomes, including early onset extramedullary disease, despite the use of novel triplet regimens [ASH abstract 4996]. Blood. 2012;120:4996.
86. Munshi NC, Avet-Loiseau H. Genomics in multiple myeloma. Clin Cancer Res. 2011;17(6):1234-1242.
87. Shaughnessy JD Jr, Qu P, Usmani S, et al. Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3. Blood. 2011;118(13):3512-3524.
88. Rajkumar SV. Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012;87(1):78-88.
89. Wuilleme S, Robillard N, Lode L, et al. Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia. 2005;19(2):275-278.
90. Chng 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(5):807-813.
91. Ahmann GJ, Jalal SM, Juneau AL, et al. A novel three-color, clone-specific fluorescence in situ hybridization procedure for monoclonal gammopathies. Cancer Genet Cytogenet. 1998;101(1):7-11.
92. Avet-Loiseau H, Facon T, Daviet A, et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res. 1999;59(18):4546-4550.
93. Moreau P, Facon T, Leleu X, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood. 2002;100(5):1579-1583.
94. De Vos J, Bagnis C, Bonnafoux L, et al. Comparison of murine leukemia virus, human immunodeficiency virus, and adeno-associated virus vectors for gene transfer in multiple myeloma: lentiviral vectors demonstrate a striking capacity to transduce low-proliferating primary tumor cells. Hum Gene Ther. 2003;14(18):1727-1739.
95. Gu ZJ, De Vos J, Rebouissou C, et al. Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors. Leukemia. 2000;14(1):188-197.
96. Dong H, Yang HS, Jagannath S, et al. Risk stratification of plasma cell neoplasm: insights from plasma cell-specific cytoplasmic immunoglobulin fluorescence in situ hybridization (cIg FISH) vs. conventional FISH. Clin Lymphoma Myeloma Leuk. 2012;12(5): 366-374.
97. Pozdnyakova O, Crowley-Larsen P, Zota V, Wang SA, Miron PM. Interphase FISH in plasma cell dyscrasia: increase in abnormality detection with plasma cell enrichment. Cancer Genet Cytogenet. 2009;189(2):112-117.
98. Smetana J, Frohlich J, Vranova V, Mikulasova A, Kuglik P, Hajek R. Oligonucleotide-based array CGH as a diagnostic tool in multiple myeloma patients. Klin Onkol. 2011;24(SUPPL):S43-S48.
99. Egan JB, Kortuem KM, Kurdoglu A, et al. Extramedullary myeloma whole genome sequencing reveals novel mutations in cereblon, proteasome subunit G2 and the glucocorticoid receptor in multi drug resistant disease. Br J Haematol. 2013;161(5):748-751.
100. Avet-Loiseau H, Li C, Magrangeas F, et al. Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol. 2009;27(27):4585-4590.
101. Adamia S, Reiman T, Crainie M, Mant MJ, Belch AR, Pilarski LM. Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma. Blood. 2005;105(12):4836-4844.
102. Dimopoulos K, Gimsing P, Gronbaek K. Aberrant microRNA expression in multiple myeloma. Eur J Haematol [published online April 15, 2013].
103. Zhan F, Tian E, Bumm K, Smith R, Barlogie B, Shaughnessy J Jr. Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development. Blood. 2003;101(3):1128-1140.
104. Decaux O, Lode L, Magrangeas F, et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2008;26(29):4798-4805.
105. Shaughnessy JD Jr, Haessler J, van Rhee F, et al. Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets: superiority of molecular genetics. Br J Haematol. 2007;137(6):530-536.
106. Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008;112(8):3115-3121.
107. van Rhee F, Szymonifka J, Anaissie E, et al. Total Therapy 3 for multiple myeloma: prognostic implications of cumulative dosing and premature discontinuation of VTD maintenance components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy. Blood. 2010;116(8):1220-1227.
108. Shaughnessy JD, Zhou Y, Haessler J, et al. TP53 deletion is not an adverse feature in multiple myeloma treated with Total Therapy 3. Br J Haematol. 2009;147(3):347-351.
109. Nair B, Shaughnessy JD Jr, Zhou Y, et al. Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival. Blood. 2009;113(26):6572-6575.
110. Moreau P, Planche L, Attal M, et al. The combination of ISS 3, high LDH and t(4;14) and/or del(17p) identify a simple prognostic index for overall survival in patients treated with novel agents-based induction therapy and frontline autologous stem cell transplantation, and allow the definition of a subgroup of patients at high-risk of early death from progressive disease [ASH abstract 598]. Blood. 2012;120:598.
111. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564-569.
112. Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999;93(1):55-65.
113. Shaughnessy J, Jacobson J, Sawyer J, et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression. Blood. 2003;101(10):3849-3856.
114. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335(2):91-97.
115. Desikan 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(12):4008-4010.
116. Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349(26):2495-2502.
117. Cavo M, Tosi P, Zamagni E, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007;25(17):2434-2441.
118. van de Velde HJ, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M. Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica. 2007;92(10):1399-1406.
119. Gay F, Larocca A, Wijermans P, et al. Complete response correlates with longterm progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011;117(11):3025-3031.
120. Paiva B, Vidriales MB, Cervero J, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008;112(10):4017-4023.
121. Rawstron AC, Davies FE, DasGupta R, et al. Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation. Blood. 2002;100(9):3095-3100.
122. Paiva B, Martinez-Lopez J, Vidriales MB, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol. 2011;29(12):1627-1633.
123. Paiva B, Gutierrez NC, Rosinol L, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood. 2012;119(3):687-691.
124. Durie BG, Jacobson J, Barlogie B, Crowley J. Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in Southwest Oncology Group chemotherapy trials. J Clin Oncol. 2004;22(10):1857-1863.
125. Lachin JM. Statistical considerations in the intent-to-treat principle. Control Clin Trials. 2000;21(3):167-189.
126. Haessler J, Shaughnessy JD Jr, Zhan F, et al. Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling. Clin Cancer Res. 2007;13(23):7073-7079.
127. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357(21):2133-2142.
128. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25(25):3892-3901.
129. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487-2498.
130. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123-2132.
131. Rajkumar SV, Gahrton G, Bergsagel PL. Approach to the treatment of multiple myeloma: a clash of philosophies. Blood. 2011;118(12):3205-3211.
132. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stemcell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782-1791.
133. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770-1781.
134. Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010;28(30):4621-4629.
135. Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol. 1998;16(12):3832-3842.
136. Soverini S, Cavo M, Cellini C, et al. Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation. Blood. 2003;102(5):1588-1594.
137. Stewart AK, Fonseca R. Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol. 2005;23(26):6339-6344.
138. Shaughnessy J Jr, 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(1):217-223.
139. Shaughnessy J. Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology. 2005;10(suppl 1):117-126.
140. Fonseca R, Debes-Marun CS, Picken EB, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003;102(7):2562-2567.