The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype.
Ontology highlight
ABSTRACT:
SUBMITTER: Schinke C
PROVIDER: S-EPMC5541885 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype.
Schinke Carolina C Hoering Antje A Wang Hongwei H Carlton Victoria V Thanandrarajan Sharmilan S Deshpande Shayu S Patel Purvi P Molnar Gabor G Susanibar Sandra S Mohan Meera M Mathur Pankaj P Radhakrishnan Muthukumar M Hoque Shadiqul S Jo Kamimoto Jorge J Grazziutti Monica M van Rhee Frits F Zangari Maurizio M Insuasti-Beltran Giovanni G Alapat Daisy D Post Ginell G Yaccoby Shmuel S Epstein Joshua J Rasche Leo L Johnson Sarah S Moorhead Martin M Willis Tom T Barlogie Bart B Walker Brian B Weinhold Niels N Davies Faith E FE Morgan Gareth J GJ
Haematologica 20170518 8
Similar Datasets
Project description:Hyperdiploidy (HRD) and specific immunoglobulin heavy locus (IGH) translocations are primary chromosomal abnormalities (CA) in multiple myeloma (MM). In this retrospective study of 794 MM patients we aimed to investigate clinical features and common CA including gain(1q) in separate subgroups defined by primary CA. In the entire group, we confirmed that gain(1q) was associated with short time to next treatment and adverse overall survival (OS). The impact was worse for four or more copies of 1q21 as compared to three copies. However, in a subgroup of patients with clonal gain(11q) and without known primary IGH translocations (CG11q), already three copies of 1q21 were associated with a poor outcome; in the absence of gain(1q), patients in this subgroup had a remarkably long median OS of more than nine years. These cases were associated with HRD, coexpression of CD56 and CD117, male gender, and IgG subtype. In non-CG11q patients, four or more copies of 1q21 (but not three copies) had a significant adverse impact on outcome. Several associations with CA and clinical findings were observed for the defined subgroups. As an example, we found a predominance of early tetraploidy, plasma cell leukemia, and female gender in the t(14;16) subgroup. Our results underscore the importance of subgrouping in MM.
| S-EPMC7756645 | biostudies-literature
Project description:Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014. The overall response rates to chemotherapy were lower in patients with high CD68+ or CD163+ TAM densities than in those with low densities. Kaplan-Meier analysis showed that the progression-free survival (PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+ TAM density were significantly higher than those of patients with high CD163+ TAM density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163 signature) exhibited greater power in predicting patient outcomes for both PFS (p < 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+ and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001, respectively). These factors could be combined with the international staging system (ISS) to generate a predictive nomogram for patient outcomes. Our findings suggest that the mosaic of diametrically polarized TAMs is a novel independent prognostic factor that could be integrated into the evaluation of and therapy for MM.
| S-EPMC5762541 | biostudies-literature
Project description: Not available
| S-EPMC10036560 | biostudies-literature
Project description:Background: Arrhythmias are common cardiovascular complications in multiple myeloma (MM) patients and are related to a poor prognosis. Objective: This study aimed to assess the burden of arrhythmias and their prognostic value in patients with MM. Methods: This was a retrospective study of patients with MM between January 2015 and April 2020 at the First Affiliated Hospital of Xi'an Jiaotong University. The incidence of arrhythmia and associated risk factors were evaluated. The relationship between the type of arrhythmia and survival was analyzed. Results: A total of 319 patients with MM were identified, and 48.0% (153/319) had arrhythmias. The most common type of arrhythmia was sinus tachycardia (ST) (15.0%, 48/319), followed by sinus bradycardia (SB) (14.4%, 46/319), premature atrial contractions (PACs) (6.3%, 20/319), conduction disorders (CDs) (6.0%, 19/319), atrial fibrillation (AF) (6.0%, 19/319), premature ventricular contractions (PVCs) (4.4%, 14/319) and paroxysmal supraventricular tachycardia (PSVT) (0.6%, 2/319). The patients with arrhythmias had higher levels of log NT-proBNP and creatinine, greater bortezomib use, and a higher incidence of diabetes than those without arrhythmias (P < 0.05). The all-cause mortality rates of patients without arrhythmias and those with AF, ST, PACs, CDs, SB, and PVCs were 50.6% (84/166), 73.7% (14/19), 60.4% (29/48), 60.0% (12/20), 52.6% (10/19), 34.8% (16/46), and 28.6% (4/14), respectively. In a subgroup analysis of patients experiencing different types of arrhythmias, patients with SB had lower all-cause mortality than patients with AF (P < 0.01). Univariate and multivariate Cox analyses showed that there was a positive statistically significant association between SB and survival (HR: 0.592 [0.352-0.998], P = 0.049) in a subgroup analysis of different arrhythmias. Conclusions: Patients with MM had a heavy arrhythmia burden, and in this study, approximately half of MM patients had arrhythmias. MM patients with SB were associated with lower all-cause mortality than those with AF. SB might be an independent positive factor for prognosis.
| S-EPMC8634844 | biostudies-literature
Project description:MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including lymphoma. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is poorly understood. We therefore elucidated the complete miRNome of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls. Unsupervised cluster analysis revealed that MM samples have a distinct microRNA expression profile. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell lymphomas revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in >85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease. Plasma cells (CD138+) cells were purified from bone marrow samples of 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls.
2010-09-29 | E-GEOD-24371 | biostudies-arrayexpress
Project description:Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20). At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3-Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2.9 months (95% CI, 1.2-NR) vs. 17.5 months (95% CI, 10.4-NR), p < 0.0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival. Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.
| S-EPMC10076306 | biostudies-literature
Project description:MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including lymphoma. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is poorly understood. We therefore elucidated the complete miRNome of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls. Unsupervised cluster analysis revealed that MM samples have a distinct microRNA expression profile. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell lymphomas revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in >85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease.
2010-09-29 | GSE24371 | GEO
Project description:Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1-8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004 and 2019. CS (t | s) was defined as the probability of surviving t years given survival of s years. Median age was 64 years. Median follow-up was 6.2 years and median overall survival from diagnosis was 7.5 years. The 5-year CS estimates at s = 0, 1, 2, 3, and 5 years were 0.64, 0.61, 0.61, 0.61, and 0.58, respectively. On multivariate analysis, age ≥ 65 and proteasome inhibitor+immunomodulatory-based induction were associated with decreased survival and increased survival, respectively, retained at 5 years. The adverse impact of 1q gain/amplification, high-risk IgH translocation, and ISS-3 was significant at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Among MM patients, 5-year CS was stable at 1-5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.
| S-EPMC10185675 | biostudies-literature
Project description:PurposeThe clinical significance and prognostic role of circulating plasma cells (CPCs) in multiple myeloma (MM) are still controversial. We conducted the first meta-analysis to clarify the correlation between CPCs and the clinicopathological features and prognosis of MM patients.MethodsA comprehensive literary search for relevant studies was performed on PubMed, Embase, Medline, CNKI (Chinese) and Web of Science databases (January 1, 1950 to December 20, 2016). The associations between CPCs and survival rate and clinicopathological parameters, including International staging system (ISS) and Durie-Salm staging system (DS) stage, were evaluated. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analysis, sensitivity analysis, and publication bias were conducted.Results11 studies covering a total of 2943 patients were included. Pooled hazard ratios (HRs) revealed that the presence of CPCs predicted aggressive disease progression (HR = 1.78, 95% CI = 1.57-2.03) and reduced overall survival (OS) (HR = 1.82, 95% CI = 1.59-2.08). Subgroup analyses demonstrated that CPCs positive patients also had poor disease progression and OS in detection methods and sampling time subsets. Moreover, the presence of CPCs was strikingly associated with increased ISS stage (OR = 2.78% CI = 1.69-4.56), but not with DS stage(OR = 1.60; 95% CI = 0.74-3.47).ConclusionsCPCs status is associated with poorer survival outcome in multiple myeloma. Additionally, increased ISS stage could be significant risk factors for the presence of CPCs.
| S-EPMC5509371 | biostudies-literature
Project description:Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.
| S-EPMC11613619 | biostudies-literature