Research Topics
| ALEXANDER KEITH STEWARTSummaryAffiliation: Mayo Clinic Country: USA Publications
Research Grants
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Detail Information
Publications
How I treat multiple myeloma in younger patientsA Keith Stewart
Mayo Clinic Arizona, Scottsdale, Boston, MA, USA
Blood 114:5436-43. 2009..When access to newer drugs is restricted participation in clinical trials should be pursued...
Analysis of PTEN deletions and mutations in multiple myelomaHong Chang
Department of Laboratory Hematology, Princess Margaret Hospital University Health Network, University of Toronto, Ont, Canada M5G 2M9
Leuk Res 30:262-5. 2006..Our results indicate that alterations of PTEN are uncommon in MM patients, and PTEN deletions tend to occur in advanced disease suggesting that they are secondary, rather than primary, events in the pathogenesis of MM...- Prognostic and therapeutic significance of myeloma genetics and gene expression profilingA Keith Stewart
Hematology Oncology, Room 3 008, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA
J Clin Oncol 23:6339-44. 2005..Importantly, we recommend that all clinical trials now adopt routine genetic testing and risk stratification... - Determinants of sensitivity to lovastatin-induced apoptosis in multiple myelomaW Wei Lynn Wong
Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Mol Cancer Ther 6:1886-97. 2007..003). These results suggest that statins may be a useful molecular targeted therapy in the treatment of a subset of MM... 
A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 TrialA Keith Stewart
Division of Hematology Oncology, Mayo Clinic in Arizona, 13400 East Shea Blvd, Scottsdale, AZ 85259, USA
Blood 121:1517-23. 2013....- Novel therapeutics in multiple myelomaA Keith Stewart
Division of Hematology Oncology, Mayo Clinic in Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, USA
Hematology 17:S105-8. 2012..Other small molecules or monoclonal antibodies with novel targets such as kinase inhibitors(AKT, CDK5) and cell surface receptors (e.g. elotuzumab) are undergoing active investigation... - A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapyA K Stewart
Department of Medicine, Division of Hematology Oncology, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA
Leukemia 21:529-34. 2007..Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options... - Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasonePrashant Kapoor
Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Blood 114:518-21. 2009..These results need confirmation in larger, prospectively designed studies... - Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patientsFrancesca Gay
Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Blood 115:1343-50. 2010..3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results... - Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myelomaJonathan J Keats
Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
Cancer Cell 12:131-44. 2007..These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma... - Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myelomaFrancesca Gay
Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Am J Hematol 85:664-9. 2010..5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results... - Targeted therapeutics for multiple myeloma: the arrival of a risk-stratified approachRafael Fonseca
Mayo Clinic, 13208 East Shea Boulevard, Collaborative Research Building 3 006, Scottsdale, AZ 85259 5494, USA
Mol Cancer Ther 6:802-10. 2007.... - Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myelomaMartha Q Lacy
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 82:1179-84. 2007..To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma... - AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignanciesMarta Chesi
Comprehensive Cancer Center, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
Cancer Cell 13:167-80. 2008.... - Mayo clinic consensus statement for the use of bisphosphonates in multiple myelomaMartha Q Lacy
Division of Hematology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 81:1047-53. 2006..These guidelines were developed in the Interest of patient safety and will be reexamined as new data emerge regarding risks and benefits... - Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activityRodger E Tiedemann
Mayo Clinic, Comprehensive Cancer Center, Division of Hematology and Oncology, Scottsdale, Arizona, USA
J Clin Invest 118:1750-64. 2008..These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies... - High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access programJoseph R Mikhael
Princess Margaret Hospital, Toronto, Ontario, Canada
Br J Haematol 144:169-75. 2009..Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM... - Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivoRodger E Tiedemann
Division of Hematology and Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ 85259, USA
Blood 113:4027-37. 2009.... - Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelinesStephen M Ansell
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 85:824-33. 2010..Autologous stem cell transplant should be considered in all eligible patients with relapsed disease... - Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6Rodger E Tiedemann
Division of Hematology Oncology, Mayo Clinic Arizona, 13400 Shea Blvd, Scottsdale, AZ 85259, USA
Blood 115:1594-604. 2010..As mice that lack GRK6 are healthy, inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma... - Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelinesShaji K Kumar
Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 84:1095-110. 2009..This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence... - Genetics and cytogenetics of multiple myeloma: a workshop reportRafael Fonseca
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
Cancer Res 64:1546-58. 2004..Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease... - Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myelomaMartha Q Lacy
Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
J Clin Oncol 27:5008-14. 2009..We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma... - Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statementAngela Dispenzieri
Division of Hematology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 82:323-41. 2007.... - Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemiaEsteban Braggio
Mayo Clinic, Scottsdale, Arizona 85259 5494, USA
Cancer Res 69:3579-88. 2009.... - Review of molecular diagnostics in multiple myelomaA Keith Stewart
Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA
Expert Rev Mol Diagn 7:453-9. 2007..This classification will identify multiple myeloma patients at high genetic risk for early progression after conventional therapies... - Acute lung toxicity related to pomalidomideHolly L Geyer
Division of Hematology Oncology, Mayo Clinic, Scottsdale, AZ, USA
Chest 140:529-33. 2011..We conclude that pulmonary toxicity is a potential adverse effect of pomalidomide therapy and encourage physicians to remain cognizant of its clinical presentation... - Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials GroupChristine I Chen
Princess Margaret Hospital, Toronto, Ontario, Canada
J Clin Oncol 25:1570-5. 2007..To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM)... - Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantationYoung Trieu
Department of Medical Oncology/Hematolog, Princess Margaret Hospital, University Health Network, Toronto, Ontario
Mayo Clin Proc 80:1578-82. 2005..6 months (95% CI, 22.1-not available months). CONCLUSION: Our data show that CP is an effective, well-tolerated, and convenient regimen as salvage therapy for MM after ASCT... - The Bcl-2 family protein inhibitor, ABT-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalanSuzanne Trudel
Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada
Clin Cancer Res 13:621-9. 2007..The aim of this study is to investigate the antimyeloma activity of a novel Bcl-2 family inhibitor, ABT-737, in preclinical treatment of multiple myeloma... - A molecular compendium of genes expressed in multiple myelomaJaime O Claudio
Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada
Blood 100:2175-86. 2002..GenBank Accession numbers include BF169967-BF176369, BF185966-BF185969, and BF177280-BF177455... - Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 confers dexamethasone resistanceJonathan B Pollett
Division of Experimental Therapeutics, Toronto General Research Institute, and the Department of Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada
Blood 100:3819-21. 2002..This finding has potential implications for the use of chemotherapy in t(4;14)-positive myeloma... - Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patientsObiageli N Onwuazor
Blood 102:772-3. 2003 - RU486-inducible retrovirus-mediated caspase-3 overexpression is cytotoxic to bcl-xL-expressing myeloma cells in vitro and in vivoJonathan B Pollett
Division of Experimental Therapeutics, Toronto General Research Institute, and Department of Medical Oncology, Princess Margaret Hospital, M5G 2M9, Toronto, Ontario, Canada
Mol Ther 8:230-7. 2003..These results indicate that therapeutic attempts to induce caspase-3 in malignant cells may prove useful in the treatment of bcl-x(L)-expressing tumors... - Detection of chromosome 13q deletions and IgH translocations in patients with multiple myeloma by FISH: comparison with karyotype analysisHong Chang
Department of Laboratory Hematology, Princess Margaret Hospital, Toronto, Canada
Leuk Lymphoma 45:965-9. 2004..Since 13q deletions, IgH translocations and a hypodiploid karyotype are significant prognostic factors for MM, our study illustrates the importance of combining conventional cytogenetics with interphase FISH analysis in patients with MM... - p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantationHong Chang
Department of Laboratory Hematology, Princess Margaret Hospital University Health Network, Toronto, ON, Canada
Blood 105:358-60. 2005..0009) or overall survival (P = .0002) in patients with MM after high-dose chemotherapy and autologous stem cell transplantation... - Results of a multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplantA Keith Stewart
Princess Margaret Hospital, Toronto, Ontario, Canada
Clin Cancer Res 10:8170-6. 2004.... - Immunohistochemistry accurately predicts FGFR3 aberrant expression and t(4;14) in multiple myelomaHong Chang
Department of Laboratory Hematology, Princess Margaret Hospital University Health Network, McLaughlin Center for Molecular Medicine, University of Toronto, ON, Canada
Blood 106:353-5. 2005..001), a shorter progression-free survival (median, 11.5 versus 25.8 months; P < .001), and a shorter overall survival (median, 19.2 versus 46.3 months; P < .001)... - Insights from the gene expression profiling of multiple myelomaJaime O Claudio
Princess Margaret Hospital, 610 University Avenue, Room 5-126, Toronto, ON M5G 2M9, Canada
Curr Hematol Rep 3:67-73. 2004..These studies are providing insight into many previously unexplained features of this difficult disease... - Clinical outcomes in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistanceWilfrid Jaksic
Department of Medical Oncology and Hematology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Canada
J Clin Oncol 23:7069-73. 2005..The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies... - MIP-1alpha (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myelomaEsther Masih-Khan
Department of Medical Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
Blood 108:3465-71. 2006..Our observation is the first to directly link an initiating IgH translocation not only to MM-cell growth and survival but also to the disease-associated bone disease... - The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cellsSuzanne Trudel
University Health Network, Princess Margaret Hospital, McLaughlin Centre of Molecular Medicine, 620 University Avenue, Rm 8204, Toronto, Ontario, Canada M5G 2C1
Blood 107:4039-46. 2006..The data demonstrate that PRO-001 is a potent and specific inhibitor of FGFR3 and deserves further study for the treatment of FGFR3-expressing myeloma... - Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trialWilliam F Clark
University of Western Ontario, London, Ontario, Canada
Ann Intern Med 143:777-84. 2005..29 mL.s(-2).m(-2) (<30 mL/min per 1.73 m2) at 6 months... - A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancerSuzane Trudel
1Division of Hematology-Oncology and Urology, The Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
Cancer Gene Ther 10:755-63. 2003..3%, range 17-69%). At higher doses, PSA values initially increased after injection, then fell to baseline prior to surgery. This trial demonstrates the feasibility and safety of intraprostatic adenovector-mediated IL-2 gene delivery... - Antigenic open reading frames from HHV-8 are present in multiple myeloma patients and normal individuals at similar frequencyYuan Xiao Zhu
Department of Medical Oncology, The Princess Margaret Hospital, Toronto General Hospital Research Institute, Ont, Canada
Leuk Lymphoma 43:369-75. 2002..HHV-8 infection appears to be common in the general population when sensitive PCR is employed and multiple samples are analyzed... - Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myelomaJoshua L Paterson
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Br J Haematol 124:595-603. 2004..Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma... - Soluble interleukin-13Ralpha2 decoy receptor inhibits Hodgkin's lymphoma growth in vitro and in vivoYoung Trieu
Division of Experimental Therapeutics, Toronto General Research Institute, McLaughlin Centre for Molecular Medicine, Toronto, Ontario, Canada
Cancer Res 64:3271-5. 2004..Our data demonstrate that AdsIL-13Ralpha2 can suppress HL growth in vitro and in vivo... - Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myelomaSuzanne Trudel
Hematology Oncology, Princess Margaret Hospital, Toronto, ON, Canada
Blood 109:5430-8. 2007..Taken together, these studies describe a novel BH3 mimic with selectivity for Mcl-1, and support the therapeutic application of GX015-070 for diverse neoplasias including multiple myeloma... - CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myelomaSuzanne Trudel
Department of Medical Oncology, University Health Network, Princess Margaret Hospital and McLaughlin Centre of Molecular Medicine, University of Toronto, 620 University Ave, Rm 8 204, Toronto, ON, Canada M5G 2C1
Blood 105:2941-8. 2005..Finally, therapeutic efficacy of CHIR-258 was demonstrated in a xenograft mouse model of FGFR3 MM. These studies support the clinical evaluation of CHIR-258 in MM... - Advances in myeloma genetics and prospects for pharmacogenomic testing in multiple myelomaJaime O Claudio
Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
Am J Pharmacogenomics 5:35-43. 2005..The use of pharmacogenomic strategies in myeloma is thus already changing medical practice... - Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myelomaDonna E Reece
Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Suite 5 207, Toronto, Ontario, M5G 2M9 Canada
J Clin Oncol 26:4777-83. 2008.... - Cyproheptadine displays preclinical activity in myeloma and leukemiaXinliang Mao
Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
Blood 112:760-9. 2008..Because the drug is well tolerated and already approved in multiple countries for clinical use as an antihistamine and appetite stimulant, it could be moved directly into clinical trials for cancer...
Research Grants
- A Genome Wide RNAi Vulnerability Map for MyelomaALEXANDER KEITH STEWART; Fiscal Year: 2010..This genomic scale analysis and the creation of a vulnerability map of Myeloma, is a prerequisite to further our global understanding of this disease and how treatments may be both personalized and optimized. ..
- The Molecular Basis for Bortezomib ActivityAlexander Stewart; Fiscal Year: 2007..The ultimate goal of our entire study will be to generate new sensitizer drugs to be used in combination therapy to increase the clinical success rate of bortezomib or other PI therapy. ..
- The Molecular Basis for Bortezomib ActivityAlexander Stewart; Fiscal Year: 2009..The ultimate goal of our entire study will be to generate new sensitizer drugs to be used in combination therapy to increase the clinical success rate of bortezomib or other PI therapy. ..
- The Molecular Basis for Bortezomib ActivityALEXANDER KEITH STEWART; Fiscal Year: 2010..The ultimate goal of our entire study will be to generate new sensitizer drugs to be used in combination therapy to increase the clinical success rate of bortezomib or other PI therapy. ..