Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3095-3100 ◽  
Author(s):  
Andy C. Rawstron ◽  
Faith E. Davies ◽  
Ranjit DasGupta ◽  
A. John Ashcroft ◽  
Russell Patmore ◽  
...  

Abstract Conventional monitoring strategies for myeloma are not sufficiently sensitive to identify patients likely to benefit from further therapy immediately after transplantation. We have used a sensitive flow cytometry assay that quantitates normal and neoplastic plasma cells to monitor the bone marrow of 45 patients undergoing high-dose chemotherapy. Neoplastic plasma cells were detectable at 3 months after transplantation in 42% of patients. Once detected, neoplastic cell levels increased steadily until clinical progression: these patients had a significantly shorter progression-free survival (PFS) (median, 20 months) than those with no detectable disease (median, longer than 35 months; P = .003). Neoplastic plasma cells were detectable in 27% (9 of 33) of immunofixation-negative complete-remission patients. These patients had a significantly shorter PFS than immunofixation-negative patients with no detectable neoplastic plasma cells (P = .04). Normal plasma cells were present in 89% of patients immediately after transplantation, but were not sustained in most cases. Patients with only normal phenotype plasma cells present at 3 months after transplantation and also at second assessment had a low risk of disease progression. Patients with neoplastic plasma cells present at 3 months after transplantation, or with only normal plasma cells present at first assessment and only neoplastic plasma cells at second assessment, had a significantly higher risk of early disease progression (P < .0001) with a 5-year survival of 54% for the high-risk group, compared with 100% in the low-risk group (P = .036). Analysis of normal and neoplastic plasma cell levels is more sensitive than immunofixation and can identify which patients may benefit from additional treatment strategies at an early stage after transplantation.

2020 ◽  
Author(s):  
Zihao Wang ◽  
Xuan Xiang ◽  
Xiaoshan Wei ◽  
Linlin Ye ◽  
Yiran Niu ◽  
...  

Abstract Background. Lung squamous cell carcinoma (LUSC) is one of the subtypes of non-small-cell lung cancer (NSCLC) and accounts for approximately 20 to 30% of all lung cancers.Methods. In this study, we developed an immune-related gene pair index (IRGPI) for early-stage LUSC from 3 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored whether IRGPI could act as a prognostic marker to identify patients with early-stage LUSC at high risk.Results. IRGPI was constructed by 68 gene pairs consisting of 123 unique immune-related genes from TCGA LUSC cohort. In the derivation cohort, the hazard of death among high-risk group was 10.51 times that of the low-risk group (HR, 10.51; 95%CI, 6.96-15.86; p<0.001). The hazard of death among the high-risk group was 2.26 times that of the low-risk group (HR, 2.26; 95%CI, 1.2-4.25; p=0.009) in the GSE37745 validation cohort and was 3.2 times that of low-risk group (HR, 3.2; 95%CI, 0.98-10.4; p=0.042) in the GSE41271 validation cohort. The infiltrations of CD8+ T cells and T follicular helper cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort (6.94% vs 9.63%, p=0.004; 2.15% vs 3%, p=0.002, respectively). The infiltrations of neutrophils, activated mast cells and monocytes were higher in the high-risk group, as compared with the low-risk group in the TCGA cohort (1.63% vs 0.72%, p=0.001; 1.64% vs 1.02%, p=0.007; 0.57% vs 0.35%, p=0.041, respectively).Conclusions. IRGPI is a significant prognostic biomarker for predicting overall survival in early-stage LUSC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qianwen Cheng ◽  
Li Cai ◽  
Yuyang Zhang ◽  
Lei Chen ◽  
Yu Hu ◽  
...  

Background: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM).Methods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves.Results: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P &lt; 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p &lt; 0.001).Conclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.


Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2091-2097 ◽  
Author(s):  
J Cortes ◽  
SM O'Brien ◽  
S Pierce ◽  
MJ Keating ◽  
EJ Freireich ◽  
...  

Although central nervous system (CNS) leukemic relapse is frequent in adult acute lymphocytic leukemia (ALL), the need for prophylaxis in different risk groups for CNS relapse, the value of high-dose systemic and intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well defined. This analysis was conducted to investigate these questions and to assess the value of a risk-oriented CNS prophylaxis approach. We analyzed the incidence of CNS leukemia after initiation of therapy in patients treated on 4 consecutive trials for adult ALL including different CNS prophylactic modalities. The treatment groups included (1) the program preceeding the vincristine-Adriamycin- dexamethasone (VAD) regimen, with no CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose systemic chemotherapy; (3) the modified VAD program with high-dose systemic chemotherapy to all patients and IT chemotherapy for high-risk patients after achieving complete remission; and (4) the hyperCVAD program with early high-dose systemic and IT chemotherapy starting during induction to all patients, with more IT injections (16IT) administered to the high-risk group for CNS relapse compared with the low-risk group (4IT). A total of 391 patients were included, 73 of whom were treated with preVAD, 112 with VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P < .001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%, and 2%, respectively (P < .001). The differences in CNS relapse rates in the low-risk group were not statistically significant. At 3 years, the overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively (P < .001). In the high-risk group, the CNS event- free rates were 38%, 66%, 75%, and 98%, respectively (P < .001); however, there was no difference in the low-risk group. We conclude that (1) high-dose systemic chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is necessary to reduce the incidence of CNS leukemia overall and in the high-risk group; and (3) a risk- oriented approach is appropriate to tailor the intensity of CNS prophylaxis.


Blood ◽  
2015 ◽  
Vol 126 (12) ◽  
pp. 1424-1432 ◽  
Author(s):  
Yong Yang ◽  
Yuan Zhu ◽  
Jian-Zhong Cao ◽  
Yu-Jing Zhang ◽  
Li-Ming Xu ◽  
...  

Key Points Patients with early-stage extranodal nasal-type NKTCL were classified as low risk or high risk using 5 independent prognostic factors. Risk-adapted therapy of RT alone for the low-risk group and RT consolidated by CT for the high-risk group proved the most effective treatment.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12561-e12561
Author(s):  
Parvaneh Fallah ◽  
Nasser Khleel Mulla ◽  
Raquel Aloyz ◽  
Olga Aleynikova ◽  
Anca Florea ◽  
...  

e12561 Background: Ki-67 is a marker of proliferating cells. The recurrence score based on the 21-gene breast cancer assay also called Oncotype Dx provides prognostic and predictive information for recurrence in early stage breast cancer patients. We previously showed that there is a moderate correlation between Ki67 and oncotype Dx recurrence score. In this retrospective study, we aimed to examine whether high Ki67 could predict the distant recurrence in early stage breast cancer with low oncotype Dx scores ( < 25). Methods: This retrospective study included 278 consecutive cases of hormone receptor-positive, HER2 negative (T1-2 N0 M0) breast cancer who were diagnosed between 2008 and 2015 with low oncotype Dx ( < 25). Patients’ clinical outcome in terms of distant recurrence after breast surgery was determined up to December 2020 (median follow-up of 7 years). Patients were divided in to low risk (Ki67 < 15%) and high risk (Ki67 > = 15%) groups. Results: Of 278 cases with average and median age of 59 and 60 respectively, 148 (53%) were in Ki67 low risk and 130 (47%) were in Ki67 high risk group. Average and median oncotype Dx were 13.86 and 15 respectively in Ki67 low risk versus 15.23 and 16 respectively in Ki67 high risk group. 13 patients (4%) experienced distant metastasis in lung, liver, bone and skin. Of these 13 cases with average and median oncotype Dx 15.84 and 19 respectively, 12 (92%) were in the Ki67 high risk group and only 1 (8%) belonged to the low risk category. High Ki67 patients were overrepresented in group with recurrent distant metastasis compare to group without recurrent disease (Pearson Chi-Square = 51.18 with 1 degree of freedom and P = < 0.001). Conclusions: Ki67 high patients in the low risk oncotype Dx group are relapsing at a significantly higher rate suggesting that Ki67 combined with low oncotype Dx further refines the risk of distant relapse.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Dongzhu Peng ◽  
Bin Gu ◽  
Liming Ruan ◽  
Xingguo Zhang ◽  
Peng Shu

Background. Gastric cancer (GC) has been divided into four molecular subtypes, of which the mesenchymal subtype has the poorest survival. Our goal is to develop a prognostic signature by integrating the immune system and molecular modalities involved in the mesenchymal subtype. Methods. The gene expression profiles collected from 6 public datasets were applied to this study, including 1,221 samples totally. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for GC (IPSGC). Results. We identified six immune genes as key factors of the mesenchymal subtype and established the IPSGC. The IPSGC can significantly divide patients into high- and low-risk groups in terms of overall survival (OS) and relapse-free survival (RFS) in discovery (OS: P<0.001) and 5 independent validation sets (OS range: P=0.05 to P<0.001; RFS range: P=0.03 to P<0.001). Further, in multivariate analysis, the IPSGC remained an independent predictor of prognosis and performed better efficiency compared to clinical characteristics. Moreover, macrophage M2 was significantly enriched in the high-risk group, while plasma cells were enriched in the low-risk group. Conclusions. We propose an immune-based signature identified by network analysis, which is a promising prognostic biomarker and help for the selection of GC patients who might benefit from more rigorous therapies. Further prospective studies are warranted to test and validate its efficiency for clinical application.


Author(s):  
Yan Fan ◽  
Hong Shen ◽  
Brandon Stacey ◽  
David Zhao ◽  
Robert J. Applegate ◽  
...  

AbstractThe purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.


Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.


2013 ◽  
Vol 95 (1) ◽  
pp. 29-33 ◽  
Author(s):  
EJC Dawe ◽  
E Lindisfarne ◽  
T Singh ◽  
I McFadyen ◽  
P Stott

Introduction The Sernbo score uses four factors (age, social situation, mobility and mental state) to divide patients into a high-risk and a low-risk group. This study sought to assess the use of the Sernbo score in predicting mortality after an intracapsular hip fracture. Methods A total of 259 patients with displaced intracapsular hip fractures were included in the study. Data from prospectively generated databases provided 22 descriptive variables for each patient. These included operative management, blood tests and co-mobidities. Multivariate analysis was used to identify significant predictors of mortality. Results The mean patient age was 85 years and the mean follow-up duration was 1.5 years. The one-year survival rate was 92% (±0.03) in the low-risk group and 65% (±0.046) in the high-risk group. Four variables predicted mortality: Sernbo score >15 (p=0.0023), blood creatinine (p=0.0026), ASA (American Society of Anaesthesiologists) grade >3 (p=0.0038) and non-operative treatment (p=0.0377). Receiver operating characteristic curve analysis showed the Sernbo score as the only predictor of 30-day mortality (area under curve 0.71 [0.65–0.76]). The score had a sensitivity of 92% and a specificity of 51% for prediction of death at 30 days. Conclusions The Sernbo score identifies patients at high risk of death in the 30 days following injury. This very simple score could be used to direct extra early multidisciplinary input to high-risk patients on admission with an intracapsular hip fracture.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jenifer Green ◽  
Connie Wolford ◽  
Jean Marc Olivot ◽  
Gregory Albers ◽  
James Castle

Background: Much controversy exists as to which TIA patients need to be admitted to the hospital for evaluation and treatment and which can be sent home. One commonly used trigae tool is the ABCD 2 score (Age, presenting Blood Pressure, Clinical symptoms and Duration, and Diabetes). Although this tool gives good information for determining populations at low risk (score of 0-3) and high risk (score of 6-7) of stroke after TIA, it leaves a large moderate risk population (score of 4-5) for whom no clear triage guidance can be given. As previous studies have found large artery atherosclerosis to be a potent risk factor for stroke after TIA, we attempted to further delineate low and high risk TIA populations with the addition of non-invasive arterial imaging to the ABCD 2 score. Methods: All patients referred to the Stanford Stroke Service for possible TIA within 72 hrs of symptom onset between July 2007 and February 2010, and all patients referred to the Highland Park Stroke Service for possible TIA within 72 hrs of symptom onset after October 2009 were screened for enrollment in this observational study. Exclusion criteria included age <18 years, use of TPA at initial presentation, and symptoms lasting >24 hours. 352 patients were invited to enroll, 3 refused. Of the 349 enrolled, follow-up was obtained in 346 patients at 30 days. Patients were placed into two groups: 1) those with ABCD 2 scores of 0-3 or scores of 4-5 AND no sign of hemodynamically significant stenosis in an artery within the distribution of the TIA (Low Risk Group); and 2) those with ABCD 2 scores of 6-7 or scores of 4-5 AND a hemodynamically significant stenosis in an artery within the distribution of the TIA (High Risk Group). Non-invasive arterial imaging included CT angiogram, MR angiogram, and carotid ultrasound - all used at the discretion of the treating physician. 30 day stroke rates with 95% confidence intervals were recorded. Results: Of the 346 patients enrolled, 295 (85.3%) fell into the "Low Risk Group" based on ABCD 2 scoring and non-invasive arterial imaging. Within that group, the stroke rate at 30 days was 1.0% (3 strokes, 95% CI 0.2-3.1%). Within the "High Risk Group", the stroke rate at 30 days was 5.9% (3 strokes, 95% CI 1.4-16.5%). Within the "Low Risk Group", all 3 of the strokes occurred in patients with ABCD 2 scores of 4-5 (3/133 patients - 2.3% stroke rate with 95% CI 0.5-6.7%). The overall stroke rate was 6/346 (1.7%, 95% CI 0.7-3.8%). Conclusions: In our observational study we found that the overall 30 day stroke rate after TIA was quite low. The percentage of all TIA patients falling into the “Low Risk Group” was quite high, and these patients had a particularly low rate of stroke at 30 days. Given the high number of "Low Risk" patients and the low rate of stroke in that group at 30 days, the vast majority of TIA patients could likely be safely evaluated in an rapid outpatient setting provided that the treating physician is confident of the diagnosis.


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