21 results on '"Ola Landgren"'
Search Results
2. Genomic and immune determinants of resistance to daratumumab-based therapy in relapsed refractory multiple myeloma
- Author
-
Bachisio Ziccheddu, Claudia Giannotta, Mattia D’Agostino, Giuseppe Bertuglia, Elona Saraci, Stefania Oliva, Elisa Genuardi, Marios Papadimitriou, Benjamin Diamond, Paolo Corradini, David Coffey, Ola Landgren, Niccolò Bolli, Benedetto Bruno, Mario Boccadoro, Massimo Massaia, Francesco Maura, and Alessandra Larocca
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Targeted immunotherapy combinations, including the anti-CD38 monoclonal antibody (MoAb) daratumumab, have shown promising results in patients with relapsed/refractory multiple myeloma (RRMM), leading to a considerable increase in progression-free survival. However, a large fraction of patients inevitably relapse. To understand this, we investigated 32 relapsed MM patients treated with daratumumab, lenalidomide, and dexamethasone (Dara-Rd; NCT03848676). We conducted an integrated analysis using whole-genome sequencing (WGS) and flow cytometry in patients with RRMM. WGS before and after treatment pinpointed genomic drivers associated with early progression, including RPL5 loss, APOBEC mutagenesis, and gain of function structural variants involving MYC and chromothripsis. Flow cytometry on 202 blood samples, collected every 3 months until progression for 31 patients, revealed distinct immune changes significantly impacting clinical outcomes. Progressing patients exhibited significant depletion of CD38-positive NK cells, persistence of T-cell exhaustion, and reduced depletion of regulatory T cells over time. These findings underscore the influence of immune composition and daratumumab-induced immune changes in promoting MM resistance. Integrating genomics and flow cytometry unveiled associations between adverse genomic features and immune patterns. Overall, this study sheds light on the intricate interplay between genomic complexity and the immune microenvironment driving resistance to Dara-Rd in patients with RRMM.
- Published
- 2024
- Full Text
- View/download PDF
3. Bortezomib, lenalidomide and dexamethasone (VRd) vs carfilzomib, lenalidomide and dexamethasone (KRd) as induction therapy in newly diagnosed multiple myeloma
- Author
-
Carlyn Rose Tan, Andriy Derkach, David Nemirovsky, Amanda Ciardiello, Benjamin Diamond, Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Urvi Shah, Kylee Maclachlan, Dhwani Patel, Oscar B. Lahoud, Heather J. Landau, David J. Chung, Gunjan L. Shah, Michael Scordo, Sergio A. Giralt, Alexander Lesokhin, Saad Z. Usmani, Ola Landgren, and Neha Korde
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Lenalidomide and dexamethasone with bortezomib (VRd) or carfilzomib (KRd) are commonly used induction regimens in the U.S. This single-center, retrospective study evaluated outcomes and safety of VRd and KRd. Primary endpoint was progression-free survival (PFS). Of 389 patients with newly diagnosed multiple myeloma, 198 received VRd and 191 received KRd. Median PFS was not reached (NR) in both groups; 5-year PFS was 56% (95%CI, 48–64%) for VRd and 67% (60–75%) for KRd (P = 0.027). Estimated 5-year EFS was 34% (95%CI, 27–42%) for VRd and 52% (45–60%) for KRd (P
- Published
- 2023
- Full Text
- View/download PDF
4. Extreme body mass index and survival in newly diagnosed multiple myeloma patients
- Author
-
Urvi A. Shah, Karissa Whiting, Sean Devlin, Rachel Ershler, Bindu Kanapuru, David J. Lee, Sabrin Tahri, Thomas Gwise, Even H. Rustad, Sham Mailankody, Alexander M. Lesokhin, Dickran Kazandjian, Francesco Maura, Daniel Auclair, Brenda M. Birmann, Saad Z. Usmani, Nicole Gormley, Catherine R. Marinac, and Ola Landgren
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
- Full Text
- View/download PDF
5. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study
- Author
-
Thorir Einarsson Long, Olafur Skuli Indridason, Runolfur Palsson, Sæmundur Rognvaldsson, Thorvardur Jon Love, Sigrun Thorsteinsdottir, Ingigerdur Solveig Sverrisdottir, Brynjar Vidarsson, Pall Torfi Onundarson, Bjarni Agnar Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdottir, Isleifur Olafsson, Asdis Rosa Thordardottir, Elias Eythorsson, Asbjorn Jonsson, Gauti Gislason, Andri Olafsson, Hlif Steingrimsdottir, Malin Hultcrantz, Brian G. M. Durie, Stephen Harding, Ola Landgren, and Sigurdur Yngvi Kristinsson
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR
- Published
- 2022
- Full Text
- View/download PDF
6. Myeloma precursor disease (MGUS) among rescue and recovery workers exposed to the World Trade Center disaster
- Author
-
Rachel Zeig-Owens, David G. Goldfarb, Benjamin J. Luft, Xiaohua Yang, Kazunori Murata, Lakshmi Ramanathan, Katie Thoren, Sital Doddi, Urvi A. Shah, Alexandra K. Mueller, Charles B. Hall, Orsi Giricz, Amit Verma, David J. Prezant, and Ola Landgren
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50–79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00–1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5–10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72–2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52–4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival.
- Published
- 2022
- Full Text
- View/download PDF
7. Structural variants shape the genomic landscape and clinical outcome of multiple myeloma
- Author
-
Cody Ashby, Eileen M. Boyle, Michael A. Bauer, Aneta Mikulasova, Christopher P. Wardell, Louis Williams, Ariel Siegel, Patrick Blaney, Marc Braunstein, David Kaminetsky, Jonathan Keats, Francesco Maura, Ola Landgren, Brian A. Walker, Faith E. Davies, and Gareth J. Morgan
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis.
- Published
- 2022
- Full Text
- View/download PDF
8. Nutrition perceptions, needs and practices among patients with plasma cell disorders
- Author
-
Maria A. Malik, Nathan W. Sweeney, Mohammad Jafri, Andriy Derkach, Cynthia Chmielewski, Peter A. Adintori, Sham Mailankody, Neha Korde, Carlyn R. Tan, Hani Hassoun, Malin Hultcrantz, Jens Hillengass, Susan E. McCann, Neil Iyengar, Saad Usmani, Sergio A. Giralt, Ola Landgren, Marcel R. M. van den Brink, Jennifer M. Ahlstrom, Alexander M. Lesokhin, Anita D’Souza, Susan Chimonas, and Urvi A. Shah
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
- Full Text
- View/download PDF
9. Body mass index and risk of progression from monoclonal gammopathy of undetermined significance to multiple myeloma: Results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
- Author
-
Vicky C. Chang, Ali A. Khan, Wen-Yi Huang, Hormuzd A. Katki, Mark P. Purdue, Ola Landgren, and Jonathan N. Hofmann
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
- Full Text
- View/download PDF
10. Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study
- Author
-
Saemundur Rognvaldsson, Elias Eythorsson, Sigrun Thorsteinsdottir, Brynjar Vidarsson, Pall Torfi Onundarson, Bjarni A. Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdóttir, Isleifur Olafsson, Hrafnhildur L. Runolfsdottir, Dadi Helgason, Arna R. Emilsdottir, Arnar S. Agustsson, Aron H. Bjornsson, Gudrun Kristjansdottir, Asdis Rosa Thordardottir, Olafur Skuli Indridason, Asbjorn Jonsson, Gauti Kjartan Gislason, Andri Olafsson, Hlif Steingrimsdottir, Petros Kampanis, Malin Hultcrantz, Brian G. M. Durie, Stephen Harding, Ola Landgren, Runolfur Palsson, Thorvarður Jon Love, and Sigurdur Yngvi Kristinsson
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81–1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52–1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.
- Published
- 2021
- Full Text
- View/download PDF
11. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies
- Author
-
Sæmundur Rögnvaldsson, Thorvardur Jon Love, Sigrun Thorsteinsdottir, Elín Ruth Reed, Jón Þórir Óskarsson, Íris Pétursdóttir, Guðrún Ásta Sigurðardóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri S. Björnsson, Gunnar Þór Gunnarsson, Runólfur Pálsson, Ólafur Skúli Indriðason, Gauti Kjartan Gíslason, Andri Ólafsson, Guðlaug Katrín Hákonardóttir, Manje Brinkhuis, Sara Lovísa Halldórsdóttir, Tinna Laufey Ásgeirsdóttir, Hlíf Steingrímsdóttir, Ragnar Danielsen, Inga Dröfn Wessman, Petros Kampanis, Malin Hultcrantz, Brian G. M. Durie, Stephen Harding, Ola Landgren, and Sigurður Yngvi Kristinsson
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
- Published
- 2021
- Full Text
- View/download PDF
12. Correction: Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies
- Author
-
Sæmundur Rögnvaldsson, Thorvardur Jon Love, Sigrun Thorsteinsdottir, Elín Ruth Reed, Jón Þórir Óskarsson, Íris Pétursdóttir, Guðrún Ásta Sigurðardóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri S. Björnsson, Gunnar Þór Gunnarsson, Runólfur Pálsson, Ólafur Skúli Indriðason, Gauti Kjartan Gíslason, Andri Ólafsson, Guðlaug Katrín Hákonardóttir, Manje Brinkhuis, Sara Lovísa Halldórsdóttir, Tinna Laufey Ásgeirsdóttir, Hlíf Steingrímsdóttir, Ragnar Danielsen, Inga Dröfn Wessman, Petros Kampanis, Malin Hultcrantz, Brian G. M. Durie, Stephen Harding, Ola Landgren, and Sigurður Yngvi Kristinsson
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
- Full Text
- View/download PDF
13. Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study
- Author
-
Ola Landgren, Bjarni A. Agnarsson, Sigrun Thorsteinsdottir, Sæmundur Rögnvaldsson, Dadi Helgason, Asbjorn Jonsson, Elias Eythorsson, Brian G.M. Durie, Gudrun Kristjansdottir, Pall T. Onundarson, Hlif Steingrimsdottir, Sigurdur Y. Kristinsson, Runolfur Palsson, Gauti Kjartan Gislason, Arnar S Agustsson, Andri Olafsson, Aron H. Bjornsson, Ingunn Thorsteinsdottir, Stephen E. Harding, Hrafnhildur Linnet Runolfsdottir, Brynjar Vidarsson, Thorvarður Jon Love, Arna R. Emilsdottir, Petros Kampanis, Olafur S. Indridason, Malin Hultcrantz, Asdis Rosa Thordardottir, Margret Sigurdardottir, and Isleifur Olafsson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Epidemiology ,Iceland ,Myeloma ,Monoclonal Gammopathy of Undetermined Significance ,Article ,Cohort Studies ,Population based cohort ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,RC254-282 ,Multiple myeloma ,Aged ,SARS-CoV-2 ,business.industry ,COVID-19 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Increased risk ,Risk factors ,Oncology ,Infectious diseases ,Female ,business ,Monoclonal gammopathy of undetermined significance ,Cohort study - Abstract
Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81–1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52–1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.
- Published
- 2021
- Full Text
- View/download PDF
14. Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma
- Author
-
Ahmet Dogan, Sham Mailankody, Amanda Ciardiello, Niccolo Bolli, Theresia Akhlaghi, Elli Papaemmanuil, Venkata Yellapantula, Ester Wasserman, Heather Landau, Dory Londono, Robert Cimera, Max Levine, Malin Hultcrantz, Yanming Zhang, Minal Patel, Juan S. Medina-Martinez, Juan E. Arango Ossa, Ola Landgren, Francesco Maura, and Even H Rustad
- Subjects
Microarray ,Concordance ,Computational biology ,Biology ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Genetics research ,Cancer genomics ,medicine ,SNP ,Gene ,Multiple myeloma ,030304 developmental biology ,0303 health sciences ,Clinical study design ,Correction ,Chromosome ,Hematology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,DNA microarray - Abstract
Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era.
- Published
- 2019
- Full Text
- View/download PDF
15. Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients
- Author
-
Elli Papaemmanuil, Sham Mailankody, Neha Korde, Malin Hultcrantz, Theresia Akhlaghi, Elizabeth M. Hill, Dickran Kazandjian, Evan H. Rustad, Mary Kwok, Ola Landgren, Alex Dew, Irina Maric, and Venkata Yellapantula
- Subjects
Neuroblastoma RAS viral oncogene homolog ,Oncology ,medicine.medical_specialty ,DNA Copy Number Variations ,Somatic cell ,Plasma cell dyscrasia ,medicine.disease_cause ,lcsh:RC254-282 ,Translocation, Genetic ,White People ,Article ,03 medical and health sciences ,Genetic Heterogeneity ,0302 clinical medicine ,Gene Frequency ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Indel ,Multiple myeloma ,Mutation ,business.industry ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Hematology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Black or African American ,030220 oncology & carcinogenesis ,Female ,KRAS ,Hyperdiploidy ,business ,Multiple Myeloma ,030215 immunology - Abstract
Caucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort. In total, 68 patient samples were successfully sequenced and manually curated based on well-established databases. Of the 68 patient samples (47 CA, 21 AA), 84% had at least one type of genomic alteration. Importantly, the IgH translocation, t(11;14), was observed more frequently in the AA group (0 vs. 29%, p = 0.001). Known oncogenic somatic non-synonymous mutations were found in 18 genes and indels in 2 genes. KRAS mutations were the most common mutation found in 16% of patients followed by NRAS and BRAF mutations. TP53 somatic mutations appeared to be more common in CA but lacked significance. This proof-of-principle study indicates the presence of varying underlying tumor biology between racial groups and supports the need of future prospective trials to capture these molecular characteristics.
- Published
- 2019
- Full Text
- View/download PDF
16. Baseline VDJ clonotype detection using a targeted sequencing NGS assay: allowing for subsequent MRD assessment
- Author
-
Mustafa H Syed, Maria E. Arcila, Even H Rustad, Caleb Ho, Yanming Zhang, Venkata Yellapantula, Malin Hultcrantz, Francesco Maura, Elli Papaemmanuil, and Ola Landgren
- Subjects
Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Genotype ,MEDLINE ,lcsh:RC254-282 ,Clonal Evolution ,Internal medicine ,Correspondence ,Genetics research ,medicine ,Cancer genomics ,Humans ,Genetic Testing ,Baseline (configuration management) ,Alleles ,business.industry ,Extramural ,High-Throughput Nucleotide Sequencing ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular Diagnostic Techniques ,VDJ Exons ,business ,Multiple Myeloma - Published
- 2020
17. Correction: Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma
- Author
-
Venkata Yellapantula, Malin Hultcrantz, Even H. Rustad, Ester Wasserman, Dory Londono, Robert Cimera, Amanda Ciardiello, Heather Landau, Theresia Akhlaghi, Sham Mailankody, Minal Patel, Juan Santiago Medina-Martinez, Juan Esteban Arango Ossa, Max Fine Levine, Niccolo Bolli, Francesco Maura, Ahmet Dogan, Elli Papaemmanuil, Yanming Zhang, and Ola Landgren
- Subjects
Oncology ,Hematology - Abstract
A correction to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
- Full Text
- View/download PDF
18. Biological determinants of health disparities in multiple myeloma
- Author
-
Cheryl J. Smith, Ola Landgren, and Stefan Ambs
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,African descent ,Review Article ,Disease ,Monoclonal Gammopathy of Undetermined Significance ,lcsh:RC254-282 ,03 medical and health sciences ,Race (biology) ,0302 clinical medicine ,Population Groups ,Epidemiology ,Prevalence ,Humans ,Medicine ,Social determinants of health ,Family history ,10. No inequality ,Multiple myeloma ,business.industry ,Cancer ,Health Status Disparities ,Hematology ,Prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,030104 developmental biology ,Oncology ,Population Surveillance ,030220 oncology & carcinogenesis ,Female ,Disease Susceptibility ,Multiple Myeloma ,business ,Demography - Abstract
Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease. In this review, we describe the relevant literature that describes the observed racial differences according to distinct tumor immunobiological and ancestral differences in populations.
- Published
- 2018
- Full Text
- View/download PDF
19. Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10–49 years old: a population-based study from the National Health and Nutrition Examination Survey
- Author
-
Ola Landgren, B I Graubard, James R. Cerhan, Jerry A. Katzmann, Malin Hultcrantz, Neha Korde, Kazunori Murata, Sham Mailankody, Robert A. Kyle, Neil E. Caporaso, Angela Dispenzieri, Shaji Kumar, S V Rajkumar, Rene Costello, Dirk R. Larson, and Terry M. Therneau
- Subjects
0301 basic medicine ,Gerontology ,Adult ,Male ,National Health and Nutrition Examination Survey ,Adolescent ,Prevalence ,Intermediate level ,Monoclonal Gammopathy of Undetermined Significance ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Medicine ,Humans ,Young adult ,Child ,Multiple myeloma ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Nutrition Surveys ,3. Good health ,Population based study ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Original Article ,Female ,Age of onset ,business ,Multiple Myeloma ,Monoclonal gammopathy of undetermined significance ,Demography - Abstract
We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10–49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23–0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62–1.26) compared with whites (0.22%, 95% CI 0.11–0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23–0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40–49 age-group; 3.26% (95% CI 2.04–5.18) versus 0.53% (95% CI 0.20–1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10–19 age-group (both Mexican-American), and in three persons in the 20–29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.
- Published
- 2017
20. The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies
- Author
-
Mattias Carlsten, Ola Landgren, Irina Maric, and Talib Dosani
- Subjects
medicine.medical_specialty ,T-Lymphocytes ,medicine.medical_treatment ,Bone Marrow Cells ,Review ,Biology ,T-Lymphocytes, Regulatory ,Blood cancer ,Immune system ,Internal medicine ,medicine ,Humans ,Multiple myeloma ,Hematology ,business.industry ,Immunotherapy ,medicine.disease ,Killer Cells, Natural ,Haematopoiesis ,medicine.anatomical_structure ,Oncology ,Immune System ,Immunology ,Cancer research ,Bone marrow ,Stem cell ,Corrigendum ,Multiple Myeloma ,business ,Monoclonal gammopathy of undetermined significance - Abstract
As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, γδ T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions.
- Published
- 2015
- Full Text
- View/download PDF
21. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies
- Author
-
Ola Landgren, Andri Olafsson, Margrét Sigurðardóttir, Asbjorn Jonsson, Manje Brinkhuis, Ásdís Rósa Þórðardóttir, Hlif Steingrimsdottir, Gunnar Þór Gunnarsson, Stephen E. Harding, Runolfur Palsson, Gauti Kjartan Gislason, Pall T. Onundarson, Guðlaug Katrín Hákonardóttir, Andri S. Bjornsson, Malin Hulcrantz, Ólafur Skúli Indriðason, Elin Ruth Reed, Ingunn Þorsteinsdóttir, Elías Sæbjörn Eyþórsson, Brian G.M. Durie, Sigurður Yngvi Kristinsson, Sara Lovísa Halldórsdóttir, Petros Kampanis, Tinna Laufey Ásgeirsdóttir, Thorvardur Jon Love, Jón Þórir Óskarsson, Inga Wessman, Brynjar Viðarsson, Bjarni A. Agnarsson, Iris Petursdottir, Sigrun Thorsteinsdottir, Ragnar Danielsen, Sæmundur Rögnvaldsson, Isleifur Olafsson, and Guðrún Ásta Sigurðardóttir
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Population ,Iceland ,Myeloma ,Early Therapy ,Monoclonal Gammopathy of Undetermined Significance ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Randomized controlled trial ,Risk Factors ,law ,Informed consent ,Humans ,Medicine ,education ,RC254-282 ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Hematology ,Middle Aged ,medicine.disease ,Biobank ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Randomized controlled trials ,Disease Progression ,Female ,Multiple Myeloma ,business ,Monoclonal gammopathy of undetermined significance ,Follow-Up Studies ,Blood sampling - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.