Venous Thromboembolism (VTE) in Patients (pts.) with Monoclonal Gammopathy of Undetermined Significance (MGUS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5340-5340
Author(s):  
Alaa A Muslimani ◽  
Fadi Bailony ◽  
Madappa Kundranda ◽  
Timothy Spiro ◽  
Asif Chaudhry ◽  
...  
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Risk Stratification ◽  
Cleveland Clinic ◽  
Risk Groups ◽  
Cancer Center ◽  
Intermediate Risk ◽  
Risk Stratification Model ◽  
Significant Difference

Abstract Introduction: MGUS is considered to be a pre-malignant condition, and previous studies have reported VTE as a marker for a subsequent malignancy. We conducted a retrospective study to evaluate the incidence of VTE among MGUS patients (pts) and to correlate this incidence with different risk groups for developing malignancy in MGUS pts. Methods: The complete medical records of all MGUS pts at Cleveland Clinic Cancer Center at Fairview hospital from Jun/2005–Jun/2008 were retrospectively reviewed. Of 237 pts diagnosed with MGUS, 112 pts (65 males, 47 females) were eligible for our study. These pts were divided into 2 risk groups: low risk (LR)/low-intermediate risk (LIR) group (78 pts.) and high intermediate risk (HIR)/high risk (HR) group (34 pts) based on the Risk Stratification Model using three adverse risk factors; serum M-protein level ≥ 3 gm/dL, non-IgG MGUS, and an abnormal kappa/lambda free light chain ratio. Only pts with ≥ 12 months follow up were included. Exclusion criteria included a personal history of inherited thrombophilia, previous episode of VTE or anticoagulant treatment, thrombocytosis, malignancy, and renal impairment. Risk factors (RF) for VTE were identified in each pt and categorized into four groups: no RF, 0; one RF, 1; two RF, 2; and > 2 RF, >2. RF included > 48 hours of immobilization, surgery in the past 3 months, current hospitalization at the time of VTE occurrence, oral contraceptive use, and congestive heart failure. Objectives: To compare the proportion of pts with MGUS who developed VTE to the proportion of pts in the general population who developed VTE. To compare VTE incidence between the two risk groups. Results: During the study period, 9 pts with MGUS experienced VTE. In the general population, the incidence of VTE is 117/100,000 persons/year (from literature). Therefore, the proportion of pts in the general population over 3 years was 117/100000 × 3 =0.0035. The proportion of VTE in MGUS pts, adjusted for 3 years, of 0.080 is significantly higher than that for the general population (p<0.001). Comparison of VTE incidence between the two risk groups, while adjusting for the number of risk factors, showed no difference (Cox Proportional Model, p=0.38). There is no significant difference in the risk of VTE among different levels of risk factors (p=0.96). The Kaplan-Meier estimates of the proportions of pts free of VTE at 24 months are 0.96 and 0.93 for the LR/LIR and HIR/HR groups, respectively. Conclusions: MGUS is associated with a significantly higher rate of VTE compared to the general population. Despite many studies indicating VTE as a marker for subsequent malignancy, we did not find a difference in the incidence of VTE among the various risk factor groups. Any suggestive signs of VTE in pts with MGUS should be promptly evaluated and treatment initiated as soon as possible. Since the number of pts is small and the period of follow-up relatively short, a prospective cohort study is needed to verify our results. Table?: Comparison of event rate: VTE Po p-value Total number of pts Risk stratification model (pts) Groups (pts) VTE Proportion Note: Po is the VTE proportion for the general population over a 3-year time period. 112 LR (38) LR/LIR (78) (5) LIR (40) 0.080 0.0035 <0.001 HIR (26) HIR/HR (34) (4) HR (8)

Proteomic Pattern-Based Risk Stratification of Outcome Shows Significant Higher Accuracy Compared to HCT-CI in Patients with AML and MDS,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4128-4128
Author(s):  
Christiane E Dobbelstein ◽  
Jochen Metzger ◽  
Elke Dammann ◽  
Uwe Borchert ◽  
Stefanie Buchholz ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
The Other ◽  
Unrelated Donor ◽  
Intermediate Risk ◽  
Significant Difference

Abstract Abstract 4128 Objectives: Allogeneic stem cell transplantation (SCT) is an established treatment for many severe disorders of hematopoiesis. Although SCT has considerable curative potential, its application is limited by transplant-related complications such as infections and graft-versus host disease (GvHD) which could lead to high mortality rates especially in older or less fit patients. Therefore, a careful pre-SCT assessment of risk and benefit is mandatory and different scores have recently emerged as helpful tools. We have previously applied proteomics to identify a specific urinary polypeptide patterns (PP) predictive for developing acute GvHD (aGvHD) (Weissinger EM et al, Blood 2007;109:5511–5519). The aim of this study was to investigate whether the PPs can predict overall outcome after allo-SCT and to compare these findings to those of the hematopoietic cell transplantation comorbidity index (HCT-CI) (Sorror M et al, Blood 2005;106:2912–2919). Methods: In this retrospective analysis from Hannover Medical School, the datasets from all patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who were allo-transplanted from a fully matched donor (matched related/unrelated donor (MRD/MUD)) between 2003–2008 and for whom relevant PP data were available, were included. Pts with a pt-donor HLA-mismatch constellation were excluded from this study. PP data from urine samples which were prospectively collected by day ≥ +7 after allo-SCT were correlated with overall survival (OS), aGvHD, non-relapse mortality (NRM), relapse rate and mortality (RM), and compared to the predictive value of the HCT-CI. Results: PP data were available from 111 pts (97 pts with AML, 14 with MDS; median age 52y; median EBMT score 4; 59 male/52 female; 69 MUD/42 MRD). They were grouped in high (PP-HRG), low (PP-LRG) or intermediate risk groups (PP-IRG). Forty-three pts (39%) belonged to the PP-LRG for aGvHD compared to 47 pts (42%) who were classified PP-HRG. Patient characteristics of PP-LRG and PP-HRG were similar in terms of age, sex and EBMT score (median 4 in both groups). OS compared favorably for the PP-LRG with an OS of 72% vs. 49% for the PP-HRG (p=0.03), also if only reduced intensity conditioning (RIC) was considered (73% vs 42%; p=0.01), respectively. There was a trend for higher incidence of NRM in the PP-HRG compared to PP-LRG (30% vs 14%, p=0.07) for the whole cohort, and a significant higher NRM rate, if only RIC was evaluated (35% vs 11%, p=0.01). However, if risk stratification was based on the HCT-CI, there was no significant difference between high risk (S-HRG) and low risk group (S-LRG) in terms of OS and NRM regardless of intensity of conditioning (OS for whole cohort: 57% vs 45%, p=0.4; OS for RIC: 56% vs 36%, p=0.2; NRM for whole cohort: 20% vs 23%, p=0.8; NRM for RIC: 18% vs 29%, p=0.4). Concerning the PP-IRG, there was a difference in OS between PP-IRG and PP-LRG (38% vs 73%, p=0.02). However, there was no significant difference in OS of the PP-IRG compared to the other PP-based risk groups nor between the HCT-CI based risk groups. Further, NRM did not show a significant difference neither for PP-based nor HCT-CI-based intermediate risk group compared to the other risk groups. Thirty vs 15 pts developed aGvHD in PP-HRG and PP-LRG (64% vs 35%, p<0.01) compared to 48% vs 64% (p=0.2) for S-HRG and S-LRG of the whole cohort, respectively. Incidence of aGvHD differed also significantly in the RIC cohort for PP-HRG and PP-LRG (65% vs 32%, p=0.01), but not for HCT-CI-based risk groups (47% vs 64%, p=0.1). Relapse rates and RM were not significantly different between high and low risk groups, neither for PP-based nor HCT-CI based (whole cohort and RIC subgroup), respectively. Conclusion: Risk stratification according to GvHD-match based PP, which has previously been shown to predict aGvHD, now also allows the identification of patient groups with significantly different OS and NRM. In comparison to the HCT-CI, PP-based prediction shows significantly higher accuracy in this rather homogeneous cohort of patients. Since proteomics is a new method which has been available only at a few centers, further multicenter analyses are essential to determinate the value of PP-based prediction of complications and outcome in SCT. Disclosures: Metzger: Mosaiques Diagnostics GmbH: Employment.

The Ratio of Monoclonal to Polyclonal Immunoglobulins Assessed with the Hevylite Test Predicts Prognosis, Is Superior for Monitoring the Course of the Disease and Allows Detection of Monoclonal Immunoglobulin In Patients with Normal or Subnormal Involved Immunoglobulin Isotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4038-4038
Author(s):  
Heinz Ludwig ◽  
Ladan Mirbahai ◽  
Niklas Zojer ◽  
Arthur Bradwell ◽  
Stephen Harding
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Risk Stratification ◽  
Binding Site ◽  
Light Chain ◽  
Monoclonal Immunoglobulin ◽  
Immunoglobulin Isotype ◽  
Site Group ◽  
Risk Stratification Model

Abstract Abstract 4038 Parameters that appraise the prognosis of an individual multiple myeloma (MM) patient are essential for clinical guidance and treatment planning. Similarly important for clinical care are factors that assess variations in the course of the disease and that allow accurate measurement of residual monoclonal proteins. Presently, the International Staging System (ISS) stage, and cytogenetics are used for prognostication, EBMT or IMWG response criteria are applied for evaluation of response and of progressive disease, and conventional protein analytics including serum free light chain (FLC) measurement, serum protein electrophoresis (SPE) and immunofixation (IF) for detection of residual paraprotein. Here, we evaluate the prognostic relevance of the ratio of monoclonal to isotype matched polyclonal immunoglobulins for prognostication at start of therapy, for evaluation of response for long term follow up and for measurement of monoclonal immunoglobulin in patients with normal or below normal levels of the involved immunoglobulin isotype. 103 previously untreated patients with multiple myeloma were enrolled (35 IgGκ, 17 IgGλ, 29 IgAκ, 22 IgAλ). 39 (38%) presented with ISS stage I, 42 (41%) with stage II, and 22 (21%) with stage III disease; there was insufficient data to assign ISS in 2 cases. Median age was 67 (range: 32,86) years. Patients were enrolled from 1994 to 2007, either into a trial comparing thalidomide-dexamethasone with Melphalan-Prednisone or into a study comparing double with triple autologous transplantation after 4 cycles of VAD induction therapy. Patients were followed for a median of 13 months (range: 85 days -158 months). Immunoglobulin heavy/light chain (HLC) pairs were assessed by using polyclonal antibodies targeted at unique junctional epitopes between heavy chain and light chain constant regions of intact immunoglobulins using the Hevylite IgA kappa, IgA lambda, IgG kappa and IgG lambda kits (HevylitêO Binding Site, Birmingham, UK) on a Siemens BN̂OII Analyzer. Concentrations of conventional parameters such as IgA, IgG, ß2-microglobulin (β2-M), FLC, immunofixation, LDH, creatinine, were assessed by standard techniques. Survival analysis and Cox proportional hazards were performed using SPSS v18 program Median OS of the entire group was 37.9 months with 39 (37 %) of the103 (6 patients were lost to follow up) patients being alive at 4 years follow up. Univariate analysis revealed a correlation between OS and β2-M, (HR: 1.411, 95% CI: 1.369–4.248, p=0.002), the HLC ratio (HR: 1.9, 95% CI: 1.092–3.36, p=0.02), and LDH (HR:1.006, 95%CI 1.00–1.014, p=0.0396) but not with Albumin, age, and creatinine. In multivariate analysis, β2-M (HR: 1.9, 95% CI: 1.105–3.93, p=0.028), and the HLC ratio (HR: 1.89, 95% 1.092–3.362: x-y, p=0.039), were found as the only parameters correlating with survival. A three tiered risk stratification model utilizing ß2-M >3.5mg/L and HLC >median value had a greater prognostic value than ISS (p=0.001 v p=0.09). Patients with 0 risk factors (ß2-M <3.5mg/L, HLC ratio <median) had a 50% survival time of 118 months, patients with 1 risk factor (either ß2-M >3.5mg/L or HLC ratio >median) had a 50% survival of 53 months and those with both risk factors (ß2-M >3.5mg/L and HLC ratio >median) had a 50% survival of 29 months (p=0.001). During follow up 46 (45%) of the patients achieved normal or subnormal levels of their involved immunoglobulin isotype. Abnormal HLC ratios were identified in 35/46, interestingly 7/35 patients (IgA kappa: 2 pts, IgA lambda: 2pts. IgG kappa: 3pts) were negative by IFE, indicating that the hevylite test is more sensitive than IF in identifying residual disease. In addition in 7/35 patients HLC ratio indicated relapse when immunoglobulin levels where within normal ranges. In conclusion, the HLC ratio is highly prognostic. Furthermore, HLC analysis improved the detection of variations in the course of the disease and increased the diagnostic accuracy in patients with normal or subnormal levels of the involved isotype and even in patients shown to ne negative in IF. Determination of the HLC ratio seems to overcome a hitherto unmet need for improvement in assessment of response and of variations in the production of the monoclonal protein.Figure 1:Risk stratification model based upon ß2-M >3.5mg/L and HLC >medianFigure 1:. Risk stratification model based upon ß2-M >3.5mg/L and HLC >median Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.

scholarly journals Surveillance of Monoclonal Gammopathy of Undetermined Significance: A Proposed Change

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1906-1906
Author(s):  
Hollie Elise Sheffield ◽  
Yu-Min Shen ◽  
Nivan Chowattukunnel ◽  
Waqas Haque
Keyword(s):  
Risk Stratification ◽  
Lower Risk ◽  
Monoclonal Gammopathy ◽  
Risk Group ◽  
Risk Groups ◽  
Bone Lesions ◽  
Evidence Based ◽  
Intermediate Risk ◽  
Undetermined Significance

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is a diagnosis that is often incidentally made after a serum protein electrophoresis (SPEP) is ordered as part of the evaluation for multiple nonspecific symptoms and is often ordered by non-hematologists. Currently, there is a lack of guidance regarding the extent of evaluation and follow-up required for these patients. Objective: Determine whether the risk stratification of the abnormal SPEP predicted progression to multiple myeloma (MM) or other lymphoplasmacytic malignancies (LPM) and could act as a guideline for appropriate follow-up in attempts to provide evidence-based, higher value care. Design: A retrospective review was performed of patients referred to the county hematology clinic for an abnormal SPEP from 2012 to 2019. The SPEP results were then risk-stratified and individual patient charts were reviewed to determine the symptomatology present at the time it was ordered, as well as the clinical course of the patients over time. Main Measures: Patients were stratified into low, low-intermediate, high-intermediate, and high risk groups for progression to MM based on the Mayo Clinic criteria. Additional information was also analyzed including the number of SPEP tests per patient, the indication stated for ordering the SPEP, and the presence of symptoms that are associated with MM at the time the SPEP was ordered, including anemia, renal failure, hypercalcemia, and bone lesions (commonly known as "CRAB symptoms"). Results: We abstracted data from 436 patients referred to the hematology clinic associated with a large county hospital system for an abnormal SPEP. The most common documented reasons for SPEP testing were increased creatinine (35%), protein gap (12%), and decreased hemoglobin (11%). Of these patients, 24 (5.5%) developed MM, 19 of whom were stratified into the high-intermediate risk group. More than a thousand SPEP results were obtained in the low and low-intermediate risk groups with only 5 patients diagnosed with MM. In the high-intermediate and low-intermediate risk groups, between 2-3 SPEP tests were performed prior to making the diagnosis of MM. In the low risk group, 6 SPEP tests were performed prior to reaching the MM diagnosis. Among the 5 patients in the low and low-intermediate risk groups who developed MM, all 5 had one or more of the CRAB symptoms at the time of the initial SPEP. Conclusion: Of the patients with MGUS who progressed to MM, approximately 80% were in the high-intermediate risk group. Of the remaining patients who progressed to MM from the lower risk groups, all had one or more of the previously mentioned CRAB symptoms, a higher percentage compared to the low and low-intermediate risk groups overall. In the absence of symptomatic disease, there is insufficient evidence to support serial SPEP testing in the lower risk patients. The use of evidence-based risk stratification may minimize unnecessary testing and hematology referrals while resulting in significant cost-savings and higher value care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

A Risk Score Integrating BAALC, ERG and WT1 Expression Can Be Used To Improve Risk Stratification In Acute Promyelocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1323-1323
Author(s):  
Anna Hecht ◽  
Florian Nolte ◽  
Daniel Nowak ◽  
Verena Nowak ◽  
Benjamin Hanfstein ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Expression Levels ◽  
Improve Risk Stratification

Abstract Introduction With current therapy regimens over 75% of patients with de novo acute promyelocytic leukemia (APL) can be cured. Approaches to further improve patient outcome by stratifying patients at the time of initial diagnosis according to their individual risk and to adjust therapy accordingly have been based on clinical features only. Molecular markers have not been established for risk stratification as yet. Recently, we have shown that high expression levels of the genes brain and acute leukemia, cytoplasmic (BAALC) and ets related gene (ERG) are associated with inferior outcome in APL patients. In addition, data indicate that aberrant expression of the gene Wilms’ tumor 1 (WT1) is a negative prognostic factor with regard to overall survival (OS) after complete remission (CR) and relapse free survival (RFS) in APL. In this study we evaluated the prognostic relevance of a combined score integrating the expression levels of the above mentioned genes to further improve risk stratification in APL patients. Methods Expression levels of BAALC, ERG and WT1 of 62 patients with newly diagnosed APL were retrospectively analyzed in bone marrow mononuclear cells using multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR). Median age of patients was 47 years (range: 19 to 82y). All patients gave informed consent. Patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) study with a treatment of simultaneous ATRA and double induction chemotherapy including high-dose ara-C, consolidation and maintenance chemotherapy. The following gene expression levels were identified as negative risk factors in preceding studies: BAALC expression ≥25th percentile (BAALChigh), ERG expression >75th percentile (ERGhigh) and WT1 expression ≤25th percentile or ≥75th percentile (WT1low/high). A risk score was developed as follows: for the presence of one of the mentioned risk factors one scoring point was assigned to a respective patient, i.e. a maximum of 3 points (one point for BAALChigh, ERGhigh and WT1low/high, respectively) and a minimum of 0 points (i.e. presenting with none of the aforementioned risk factors) could be allocated to one patient. Accordingly, patients were divided into four risk groups: 7 patients scored 0 points (= low risk), 27 patients scored 1 point (= intermediate 1 risk), 19 patients scored 2 points (= intermediate 2 risk) and 9 patients scored 3 points (= high risk). Subsequently, OS, RFS and relapse free interval (RFI) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the four risk groups (p<0.05). Results The integrative risk score divided patients into four groups with significantly different outcome. The low risk group showed a RFS of 100% at 10 years of follow-up compared to the intermediate 1 risk group with 81%, the intermediate 2 risk group with 58% and the high risk group with a RFS of 42% only (median survival: 4.6y) (p=0.02). In accordance, the RFI differed significantly between the four groups: low risk 100%, intermediate 1 risk 100%, intermediate 2 risk 89% and high risk 71% (p=0.049). There was no statistically significant difference between the 4 groups with regard to OS in the entire patient cohort. However, there was a clear trend towards a difference in OS in patients who achieved a CR after induction therapy: low risk 100%, intermediate 1 risk 81%, intermediate 2 risk 68% and high risk 53% survival at 10 years of follow-up (p=0.09). Conclusion Integration of expression levels of the genes BAALC, ERG and WT1 into a scoring system identifies 4 risk groups with significantly different outcome with regard to RFS and RFI. It might be a promising approach to guide therapeutic decisions in patients with APL. However, multivariate analyses and validation of these data in an independent patient cohort is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk stratification for prediction of locoregional recurrence in patients with pathologic T1–2N0 breast cancer after mastectomy

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianyang Wang ◽  
Yu Tang ◽  
Hao Jing ◽  
Guangyi Sun ◽  
Jing Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Risk Stratification ◽  
Locoregional Recurrence ◽  
Risk Model ◽  
Tumor Location ◽  
Cancer Center ◽  
Breast Cancers ◽  
Independent Risk Factors

Abstract Background Previous studies have revealed that nearly 15–20% of selected high-risk T1–2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1–2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). Methods Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. Results A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1–222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1–2, and 3–4 risk factors (p < 0.001). Conclusions Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1–2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3–4 risk factors.

Front-Line Treatment of Acute Promyelocytic Leukemia with AIDA Induction Followed by Risk-Adapted Consolidation: Results of the AIDA-2000 Trial of the Italian GIMEMA Group.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 392-392 ◽  
Author(s):  
Francesco Lo Coco ◽  
Giuseppe Avvisati ◽  
Marco Vignetti ◽  
Giuseppe Fioritoni ◽  
Vincenzo Liso ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Groups ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Front Line ◽  
High Risk Disease ◽  
Significant Difference ◽  
Outcome Improvement

Abstract Following the identification, in collaboration with the Spanish PETHEMA group, of distinct prognostic categories among APL patients receiving AIDA-like therapies (Sanz et al. Blood 2000) the Italian GIMEMA group designed a protocol for newly diagnosed APL (AIDA-2000) in which the intensity of post-remission treatment was adapted to the relapse risk. A total of 298 PML/RARa-positive patients with median age 40 yrs (range 1–60) were enrolled during the period January 2000 – February 2003 from 64 Italian institutions. After the standard AIDA-0493 induction (Mandelli et al, Blood 1997), patients with low- and intermediate-risk received 3 anthracycline-based consolidation courses with idarubicin, mitoxantrone, and idarubicin as in the PETHEMA LPA-96 (Sanz et al. Blood 1999), whereas patients with high-risk disease (WBC > 10 x 109/L) received the same 3 anthracycline courses with the addition of cytarabine, etoposide and cytarabine plus 6-thioguanine during the first, second and third course, respectively, as in the original AIDA. In addition, distinct from those in the AIDA-0493, all patients enrolled in the AIDA-2000 received concomitant ATRA 45 mg/m2 for 15 d during each consolidation course. The results of the AIDA-2000 series were compared to those obtained in 346 consecutive patients (median age 36 yrs, range 1–60) enrolled in the AIDA-0493 study during the period May 1997 – May 2000. All patients in either studies who tested PCR-negative post-consolidation received ATRA maintenance for a total of two years. After induction, 323/338 (96%) and 276/294 (94%) evaluable patients achieved CR in the AIDA-0493 and AIDA-2000, respectively (P=0.34). Molecular remission was obtained after consolidation in 291/296 (98%) and 235/238 (99%) patients (P=0.69). With a median follow-up of 4.5 and 2.0 yrs in the two studies, the DFS at 2.0 yrs for patients in the AIDA-0493 and AIDA-2000 was 84% and 90%, respectively (P=0.09), whereas the CIR rate at 2.0 yrs was 14% and 5%, respectively (P=0.04). Five and 9 patients died in CR in the two series and were equally distributed among risk groups. By comparing separately the distinct risk groups in the AIDA-0493 and AIDA-2000, there was no significant difference in the CIR rate for low- (3% vs. 2%) and intermediate-risk (11% vs. 9%) groups, while a significantly higher CIR was observed in the AIDA-0493 for high-risk (29% vs. 2%, P=0.0004). In line with recent PETHEMA results, our data confirm that anthracycline-based consolidation is equally effective as cytarabine-containing regimens for patients with low- and intermediate-risk and suggest that a risk-adapted strategy including ATRA for consolidation provides an outcome improvement in newly diagnosed APL. In addition, our results suggest a benefit in terms of relapse rate reduction using cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group.

scholarly journals International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)

2020 ◽  
Vol 10 (10) ◽  
Author(s):  
María-Victoria Mateos ◽  
Shaji Kumar ◽  
Meletios A. Dimopoulos ◽  
Verónica González-Calle ◽  
Efstathios Kastritis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Low Risk ◽  
Intermediate Risk ◽  
Smoldering Multiple Myeloma ◽  
Risk Stratification Model ◽  
Risk Of Progression ◽  
Progression Risk

Abstract Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.

Regional Cervical Plexus Blockage for Carotid Endarterectomy in Patients with Cardiovascular Risk Factors

2015 ◽  
Vol 18 (4) ◽  
pp. 140 ◽  
Author(s):  
Mehmet Taşar ◽  
Mehmet Kalender ◽  
Okay Güven Karaca ◽  
Ata Niyazi Ecevit ◽  
Salih Salihi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Carotid Endarterectomy ◽  
Regional Anesthesia ◽  
Carotid Artery Disease ◽  
Risk Groups ◽  
Cardiac Risk ◽  
Cervical Plexus ◽  
Cardiac Risk Factors ◽  
Significant Difference

Background: Carotid artery disease is not rare in cardiac patients. Patients with cardiac risk factors and carotid stenosis are prone to neurological and cardiovascular complications. With cardiac risk factors, carotid endarterectomy operation becomes challenging. Regional anesthesia is an alternative option, so we aimed to investigate the operative results of carotid endarterectomy operations under regional anesthesia in patients with cardiac risk factors. <br />Methods: We aimed to analyze and compare outcomes of carotid endarterectomy under regional anesthesia with cardiovascular risk groups retrospectively. Between 2006 and 2014, we applied 129 carotid endarterectomy ± patch plasty to 126 patients under combined cervical plexus block anesthesia. Patients were divided into three groups (high, moderate, low) according to their cardiovascular risks. Neurological and cardiovascular events after carotid endarterectomy were compared.<br />Results: Cerebrovascular accident was seen in 7 patients (5.55%) but there was no significant difference between groups (P &gt; .05). Mortality rate was 4.76% (n = 6); it was higher in the high risk group and was not statistically significant (P = .180). Four patients required revision for bleeding (3.17%). We did not observe any postoperative surgical infection.<br />Conclusion: Carotid endarterectomy can be safely performed with regional cervical anesthesia in all cardiovascular risk groups. Comprehensive studies comparing general anesthesia and regional anesthesia are needed. <br /><br />

scholarly journals Premature STEMI in Men and Women: Current Clinical Features and Improvements in Management and Prognosis

2021 ◽  
Vol 10 (6) ◽  
pp. 1314
Author(s):  
Rebeca Lorca ◽  
Isaac Pascual ◽  
Andrea Aparicio ◽  
Alejandro Junco-Vicente ◽  
Rut Alvarez-Velasco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
General Population ◽  
Cardiovascular Risk Factors ◽  
Young Women ◽  
Artery Dissection ◽  
Men And Women ◽  
High Prevalence

Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. Methods: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014–31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). Results: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. Conclusion: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04–98.04), 95.64% (95% CI 92.87–97.35), and 94.5% (95% CI 91.12–97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.

HIV may indirectly accelerate coronary artery disease through enhancing the effects of conventional and non-conventional cardiovascular risk factors

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Kolossvary ◽  
E.K Fishman ◽  
G Gerstenblith ◽  
D.A Bluemke ◽  
R.N Mandler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Hiv Infection ◽  
Cardiovascular Risk Factors ◽  
Agatston Score ◽  
Funding Source ◽  
Significant Difference ◽  
Ascvd Risk ◽  
Artery Disease

Abstract Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated. Purpose In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA). Methods Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3 years). Agatston-score, number of coronary plaques, segment stenosis score were calculated, and we also segmented the coronary plaques to enumerate total, noncalcified (−100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CCTA markers of CAD. Results In univariate analysis, there was no significant difference in CAD characteristics between HIV-infected and -uninfected, neither at baseline nor at follow-up (p&gt;0.05 for all). Furthermore, there was no significant difference in annual progression rates between the two groups (p&gt;0.05 for all). By multivariate analysis, HIV was not associated with any CAD parameter (p&gt;0.05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p&lt;0.05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p&lt;0.05). These associations were only present among HIV-infected individuals. Conclusion(s) Instead of directly worsening CAD, HIV may promote CAD through increased susceptibility to conventional and nonconventional cardiovascular risk factors. Therefore, aggressive management of both conventional and nonconventional cardiovascular risk factors is needed to reduce cardiovascular burden of HIV-infection. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Institute on Drug Abuse

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