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128 citation(s) found for "C, O'Donovan".

Distress Management, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology
Riba, Michelle B., Donovan, Kristine A. , Andersen, Barbara L. , Braun, IIana, Breitbart, William , Brewer, Benjamin W. , Buchmann, Luke, Clark, Matthew M. , Collins, Molly, Corbett, Cheyenne , Fleishman, Stewart B., Garcia, Sofia F. , Greenberg, Donna, Handzo, Rev. George F., Hoofring, Laura, Huang, Chao‐Hui , Martin, Sara , McGuffey, Lisa, Mitchell, William M. , Morrison, Laura , Pailler, Megan E. , Parnes, Francine, Pazar, Janice P., Ralston, Laurel, Salman, Jaroslava, Shannon-Dudley, Moreen, Valentine, Alan , McMillian, Nicole R., Darlow, Susan, Garcia, Sofia F , Handzo, Rev. George F., Lally, Robin Mary , Mitchell, William, Palesh, Oxana Gronskaya

Journal of the National Comprehensive Cancer Network | October 7, 2019 | Volume: 17 | Issue: 10 | Pages: 1229-1249

10.6004/jnccn.2019.0048 | PMID 31590149 Get It

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.
Performance evaluation of computed tomography systems: Summary of AAPM Task Group 233
Bakalyar, Donovan, Boedeker, Kirsten , Fan, Jiahua , Myers, Kyle J. , Popescu, Lucreţiu M. , Giraldo, Juan Carlos Ramírez, Ranallo, Frank N. , Solomon, Justin , Vaishnav, J. Y., Wang, Jia , Samei, Ehsan , Brady, Samuel L. , Leng, Shuai , Vaishnav, Jay

Medical Physics | August 13, 2019 | Volume: 46 | Issue: 11 | Pages: No page available

10.1002/mp.13763 | PMID 31408540 Get It

Background The rapid development and complexity of new x‐ray computed tomography (CT) technologies and the need for evidence‐based optimization of image quality with respect to radiation and contrast media dose call for an updated approach towards CT performance evaluation. Aims This report offers updated testing guidelines for testing CT systems with an enhanced focus on the operational performance including iterative reconstructions and automatic exposure control (AEC) techniques. Materials and Methods The report was developed based on a comprehensive review of best methods and practices in the scientific literature. The detailed methods include the assessment of 1) CT noise (magnitude, texture, nonuniformity, inhomogeneity), 2) resolution (task transfer function under varying conditions and its scalar reflections), 3) task‐based performance (detectability, estimability), and 4) AEC performance (spatial, noise, and mA concordance of attenuation and exposure modulation). The methods include varying reconstruction and tube current modulation conditions, standardized testing protocols, and standardized quantities and metrology to facilitate tracking, benchmarking, and quantitative comparisons. Results The methods, implemented in cited publications, are robust to provide a representative reflection of CT system performance as used operationally in a clinical facility. The methods include recommendations for phantoms and phantom image analysis. Discussion In line with the current professional trajectory of the field toward quantitation and operational engagement, the stated methods offer quantitation that is more predictive of clinical performance than specification‐based approaches. They can pave the way to approach performance testing of new CT systems not only in terms of acceptance testing (i.e., verifying a device meets predefined specifications), but also system commissioning (i.e., determining how the system can be used most effectively in clinical practice). Conclusion We offer a set of common testing procedures that can be utilized towards the optimal clinical utilization of CT imaging devices, benchmarking across varying systems and times, and a basis to develop future performance‐based criteria for CT imaging.
Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era
Gerson, James N. , Villa, Diego , Gerrie, Alina S. , Chapani, Parv , Medeiros, L. Jeffrey , Wang, Michael I., Cohen, Jonathon B. , Calzada, Oscar , Churnetski, Michael C. , Hill, Brian T. , Sawalha, Yazeed , Hernandez‐Ilizaliturri, Francisco J. , Kothari, Shalin , Bast, Martin, Fenske, Timothy S. , Gari, Swapna Narayana Rao, Maddocks, Kami J. , Bond, David A. , Bachanová, Veronika , Kolla, Bhaskar , Lansigan, Frederick , Donovan, Alexandra M., Wagner‐Johnston, Nina D. , Messmer, Marcus , Anderson, Jennifer K., Reddy, Nishitha , Kovach, Alexandra E. , Glenn, Martha, Inwards, David J. , Karmali, Reem , Kaplan, Jason , Rajguru, Saurabh, Evens, Andrew M. , Klein, Andreas K. , Umyarova, Elvira , Pulluri, Bhargavi , Amengual, Jennifer E. , Diefenbach, Catherine , Fisher, Richard I., Bachanova, Veronika , Sawalha, Yazeed , Gerrie, Alina S , Evens, Andrew M , Karmali, Reem , Bond, David A , Medeiros, L Jeffrey , Lansigan, Frederick , Diefenbach, Catherine S , Kovach, Alexandra E , Handorf, Elizabeth A. , Li, Shaoying , Vose, Julie M. , Chavez, Julio C , Shah, Bijal , Burns, Timothy Francis , Mehta, Amitkumar , Landsburg, Daniel J. , Caimi, Paolo F. , Lue, Jennifer Kimberly , Barta, Stefan K

Journal of Clinical Oncology | January 7, 2019 | Volume: 37 | Issue: 6 | Pages: 471-480

10.1200/jco.18.00690 | PMID 30615550 Get It

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.
Revising Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition, criteria for the bipolar disorders: Phase I of the AREDOC project
Tavella, Gabriela , Berk, Michael , Grunze, Heinz , Deckersbach, Thilo , Dünner, David L., Amsterdam, Jay D., Ketter, Terence A. , Yatham, Lakshmi N. , Kessing, Lars Vedel , Bassett, Darryl, Fountoulakis, Kostas N, Duffy, Anne , Alda, Martin , Sharma, Verinder , Singh, Manpreet K. , Hájek, Tomáš , Boyce, Philip , Frey, Benício N. , Castle, David , Young, Allan H. , Vieta, Eduard , Swartz, Holly A. , Schaffer, Ayal , Murray, Greg , Bayes, Adam , Lam, Raymond W. , Post, Robert M, Ostacher, Michael J. , Lafer, Beny , Cleare, Anthony J. , O’Donovan, Claire , Ortiz, Abigail, Henry, Chantal , Kanba, Shigenobu, Rosenblat, Joshua D. , Parikh, Sagar V. , Bond, David J. , Goldberg, Joseph F. , Orum, Margo, Osser, David N. , Frye, Mark A. , Manicavasagar, Vijaya , Carlson, Gabrielle A. , Malhi, Gin S. , Fountoulakis, Konstantinos Ν. , Vieta, E , Grunze, Heinz , Bond, David J , Hajek, Tomas , Alda, Martin , Fountoulakis, Konstantinos N , Yatham, Lakshmi N , Young, Allan H , Cleare, Anthony J , Berk, Michael , Ortiz, Abigail , Parker, Gordon Barraclough , MacQUEEN, GLENDA M. , Sajatovic, Martha , Zimmerman, Mark A. , Fountoulakis, Kostas N, Calkin, Cynthia , Anand, Amit , Rybakowski, Janusz K , Bora, Emre , Post, Robert M, Burdick, Katherine E. , Grunebaum, Michael F. , Frangou, Sophia , McIntyre, Roger S. , Fagiolini, Andrea , Swartz, Holly A , Kessing, L V , Malhi, Gin S , Ostacher, Michael J

Australian & New Zealand Journal of Psychiatry | October 31, 2018 | Volume: 52 | Issue: 12 | Pages: 1173-1182

10.1177/0004867418808382 | PMID 30378461 Get It

Objective: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. Method: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. Results: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge ‘impairment’ (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. Conclusion: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.
Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
Adams, Charleen D. , Richmond, Rebecca C. , Ferreira, Diana L. Santos , Spiller, Wes , Tan, Vanessa Y. , Würtz, Peter , Donovan, Jenny , Hamdy, Freddie C. , Neal, David E. , Lane, J. Athene , Smith, George Davey , Relton, Caroline L. , Eeles, Rosalind A. , Haiman, Christopher A. , Schumacher, Fredrick R. , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Berndt, Sonja I., Conti, David V. , Gapstur, Susan M. , Stevens, Victoria L. , Batra, Jyotsna , Grönberg, Henrik , Pashayan, Nora , Schleutker, Johanna , West, Catharine , Mucci, Lorelei A. , Koutros, Stella , Sørensen, Karina D. , Mæhle, Lovise, Travis, Ruth C. , Rosenstein, Barry S. , Lu, Yong‐Jie , Kibel, Adam S. , Vega, Ana , Stanford, Janet L. , Nordestgaard, Børge G. , Maier, Christiane, Kim, Jeri , John, Esther M. , Teixeira, Manuel R. , Newcomb, Lisa F., Lessel, Davor , Kaneva, Radka , Usmani, Nawaid , Claessens, Frank , Townsend, Paul A. , Dominguez, Manuela Gago, Roobol, Monique J. , Ménégaux, F. , Pandha, Hardev , Thibodeau, Stephen N. , Martin, Richard M. , Teixeira, Manuel R , Vega, Ana , Eeles, Rosalind A , John, Esther M , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Lessel, Davor , Koutros, Stella , Martin, Richard M , Conti, David V , Batra, Jyotsna , Davey Smith, George , Zheng, Jie , Kote‐Jarai, Zsofia , Berndt, Sonja I. , Wiklund, Fredrik E. , Chanock, Stephen Jacob , Tangen, Catherine M. , Clements, Judith A. , Albanes, Demetrius , Wolk, Alicja , Cancel‐Tassin, Géraldine , Hamilton, Robert J , Ingles, Sue A. , Giles, Graham G. , Kogevinas, Manolis , Penney, Kathryn , Park, Jong Y. , Cybulski, Cezary , Brenner, Hermann , Neuhausen, Susan L. , Ruyck, Kim De , Razack, Azad Hassan Abdul , Khaw, Kay‐Tee , Cannon‐Albright, Lisa , Claessens, Frank

Cancer Epidemiology, Biomarkers & Prevention | October 23, 2018 | Volume: 28 | Issue: 1 | Pages: 208-216

10.1158/1055-9965.epi-18-0079 | PMID 30352818 Get It

Abstract Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P &lt; 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
O3‐03‐01: MECHANISTIC AND DIRECTIONAL TRANSCRIPTIONAL REGULATORY NETWORKS IN ALZHEIMER'S DISEASE
Funk, Cory C. , Richards, Matthew A., Shannon, Paul , Robinson, Max , Allen, Mariet , Carrasquillo, Minerva M. , Chakrabarty, Paramita , Jung, Segun, Ertekin‐Taner, Nilüfer , Golde, Todd E. , Ament, Seth A. , Donovan-Maiye, Rory , Rappaport, Noa , Carrasquillo, Minerva M. , McFarland, Karen N. , Rodriguez, Alex C. , Hood, Leroy , Foster, Ian T , Madduri, Ravi , Price, Nathan D.

Alzheimer's & Dementia | October 22, 2018 | Volume: 14 | Issue: 7S_Part_19 | Pages: No page available

10.1016/j.jalz.2018.06.2782 Get It

Decreased copy number aberrations in genomes of HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary durable complete responses (dCR) to trastuzumab (T).
Maguire, Alanna , Gullo, Giuseppe , Quinn, Cecily , Malasi, Smriti, Lenkiewicz, Elizabeth, Barrett, Michael T. , O’Donovan, Norma , Walsh, Naomi , Crown, John

Journal of Clinical Oncology | September 6, 2018 | Volume: 34 | Issue: 15_suppl | Pages: 610-610

10.1200/jco.2016.34.15_suppl.610 Get It

The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
Gerrish, Amy , Russo, Giancarlo , Richards, Alexander , Moskvina, Valentina, Ivanov, Dobril , Harold, Denise , Sims, Rebecca , Abraham, Richard, Hollingworth, Paul, Chapman, Jade , Hamshere, Marian L. , Pahwa, Jaspreet Singh, Dowzell, Kimberley, Jones, Nicola, Thomas, Charlene , Stretton, Alexandra, Morgan, Angharad R., Lovestone, Simon , Powell, John , Proitsi, Petroula , Brayne, Carol , Gill, Michael , Lynch, Aoibhinn, Morgan, Kevin , Brown, Kristelle, Passmore, Peter , Craig, David W. , McGuinness, Bernadette , Todd, Stephen , Johnston, Janet, Smith, A. David , Love, Seth , Kehoe, Patrick G. , Hardy, John , Mead, Simon , Fox, Nick C. , Rossor, Martin N. , Collinge, John, Maier, Wolfgang, Jessen, Frank , Kölsch, Heike, Schürmann, Britta, Bussche, Hendrik van den, Heuser, Isabella , Kornhuber, Johannes , Wiltfang, Jens , Dichgans, Martin , Frölich, Lutz, Hampel, Harald , Hüll, Michael, Goate, Alison , Kauwe, John, Cruchaga, Carlos , Nowotny, Petra, Morris, John C. , Mayo, Kevin H. , Livingston, Gill , Gurling, Hugh, McQuillin, Andrew , Gwilliam, Rhian, Deloukas, Panagiotis, Davies, Gail , Starr, John M. , Deary, Ian J. , Al‐Chalabi, Ammar , Shaw, Christopher E. , Tsolaki, Magda , Singleton, Andrew B., Guerreiro, Rita , Mühleisen, Thomas W. , Nöthen, Markus M. , Moebus, Susanne , Jöckel, Karl‐Heinz , Klopp, Norman, Wichmann, H‐Erich, Carrasquillo, Minerva M., Younkin, Steven G., Jones, Lesley , Holmans, Peter , O‘Donovan, Michael , Williams, Julie , Deloukas, Panos , Escott‐Price, Valentina , Denning, Nicola , Dichgans, Martin , Cruchaga, Carlos , Kornhuber, Johannes , Nöthen, Markus M , Hardy, John , Moebus, Susanne , Williams, Amy L. , Lupton, Michelle K. , Rubinsztein, David Chaim , LAWLOR, BRIAN A. , Holmes, Clive , Mann, David , Heun, Reinhard , Rujescu, Dan , Bass, Nicholas , Harris, Sarah , Carrasquillo, Minerva M. , Pankratz, V. Shane , Owen, Michael J. , Fox, Nick C , Morris, John C , Wiltfang, Jens , Al-Chalabi, Ammar , Tsolaki, Magda , Goate, Alison M , McQuillin, Andrew , Escott-Price, Valentina

Journal of Alzheimer's Disease | May 16, 2018 | Volume: 28 | Issue: 2 | Pages: 377-387

10.3233/jad-2011-110824 | PMID 22027014 Get It

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder
Amare, Azmeraw T. , Schubert, Klaus Oliver , Clark, Scott R. , Papiol, Sergi , Heilbronner, Urs , Degenhardt, Franziska , Tekola‐Ayele, Fasil , Hsu, Yi‐Hsiang , Shekhtman, Tatyana , Adli, Mazda , Akula, Nirmala , Akiyama, Kazufumi , Ardau, Raffaella , Arias, Bárbara , Aubry, Jean‐Michel , Bhattacharjee, Abesh Kumar, Benabarre, Antonio , Bengesser, Susanne , Birner, Armin , Brichant‐Petitjean, Clara, Cervantes, Pablo , Chen, Hsi‐Chung , Chillotti, Caterina , Cichon, Sven , Cruceanu, Cristiana , Czerski, Piotr M. , Dalkner, Nina , Zompo, Maria Del , Étain, Bruno , Falkai, Peter , Forstner, Andreas J. , Frisén, Louise , Frye, Mark A. , Fullerton, Janice M. , Gard, Sébastien, Grigoroiu‐Serbânescu, Maria , Grof, Paul , Hashimoto, Ryota , Jamain, Stéphane , Jiménez, Esther , Kahn, Jean‐Pierre, Kassem, Layla, Kuo, Po‐Hsiu , Kato, Tadafumi , Kittel‐Schneider, Sarah , Kliwicki, Sebastian , Laje, Gonzalo, Landén, Mikael , Lavebratt, Catharina , Leboyer, Marion , Leckband, Susan G. , Tortorella, Alfonso , Manchia, Mirko , Martinsson, Lina , McCarthy, Michael J. , Mitjans, Marina , Mondimore, Francis M. , Nöthen, Markus M. , Novák, Tomáš , O’Donovan, Claire , Ozaki, Norio , Ösby, Urban, Pfennig, Andrea , Potash, James B. , Reif, Andreas , Reininghaus, Eva Z. , Schalling, Martin , Schofield, Peter R. , Schweizer, Barbara , Severino, Giovanni , Shilling, Paul D. , Shimoda, Katzutaka, Simhandl, Christian , Slaney, Claire , Stamm, Thomas , Stopková, Pavla , Maj, Mario , Turecki, Gustavo , Vieta, Eduard , Volkert, Julia, Zandi, Peter P. , Bauer, Michael , Alda, Martin , McMahon, Francis J. , Etain, B , Vieta, E , Schofield, Peter R , Cichon, Sven , Nöthen, Markus M , Alda, Martin , Fullerton, Janice M , Hou, Liping , Backlund, Lena , Bellivier, Frank , Biernacka, Joanna M. , Dalkner, Nina , Dayer, Alexandre G. , DePaulo, J Raymond , Garnham, Julie , Goes, Fernando , Hauser, Joanna , Herms, Stefan , Hoffmann, Per , Hofmann, Andrea , Kelsoe, John R , König, Barbara , Kusumi, Ichiro , McElroy, Susan L. , Colom, Francesc , Monteleone, Palmiero , Nievergelt, Caroline M , Reininghaus, Eva , Rouleau, Guy Armand , Rybakowski, Janusz K , Squassina, Alessio , Witt, Stephanie H. , Wright, A. Jordan , Mitchell, Philip B , Rietschel, Marcella , Schulze, Thomas , Baune, Bernhard , Amare, Azmeraw , Papiol, Sergi , Heilbronner, Urs , Chen, Hsi-Chung , Cruceanu, Cristiana , Czerski, Piotr , Jamain, Stéphane , Grigoroiu-Serbanescu, Maria , Kuo, Po-Hsiu , Kittel-Schneider, Sarah , Lavebratt, Catharina , Leboyer, Marion , Tortorella, Alfonso , McCarthy, Michael , Novak, Tomas , Reif, Andreas , Stopkova, Pavla , Turecki, Gustavo , McMahon, Francis , Arias, Bárbara , Hashimoto, Ryota , Ozaki, Norio , Schubert, Klaus Oliver , Kato, Tadafumi , Mitjans, Marina , Manchia, Mirko

JAMA Psychiatry | November 15, 2017 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1001/jamapsychiatry.2017.3433 | PMID 29121268 Get It

Biology of the Transition of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma
Lust, John A., Donovan, Kathleen A., Lust, JA

Cancer Control | August 30, 2017 | Volume: 5 | Issue: 3 | Pages: 209-217

10.1177/107327489800500301 | PMID 10761054 Get It

Background Approximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma. Methods Studies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL- 6 and IL-1β, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed. Results IL-1β is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1β has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these “fixed” monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1β and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index. Conclusions A better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.