High WT1 Expression Has An Independent Positive Influence On CR Rate and EFS in Non M3 AML Patients Treated with Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4675-4675
Author(s):  
Nicoletta Colombo ◽  
Raffaella Grasso ◽  
Maurizio Miglino ◽  
Marino Clavio ◽  
Gianmatteo Pica ◽  
...  
Keyword(s):  
Regression Model ◽  
Prognostic Value ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Categorical Variables ◽  
P Value ◽  
Prognostic Impact ◽  
Chi Square Analysis ◽  
The Impact

Abstract Abstract 4675 The prognostic value of WT1 expression at diagnosis is still controversial. It has been retrospectively evaluated in 99 consecutive non pretreated non M3 AML patients who had undergone a complete prognostic work up at diagnosis and had received intensive chemotherapy. Biological markers were evaluated on fresh marrow samples collected at diagnosis. WT1 expression was evaluated using TaqMan Gene Expression Assays as described. All patients received induction therapy with combination of fludarabine, Ara-C and anthracycline ± low dose gemtuzumab ozogamicin (n. 59) or with a conventional combination of Ara-C and anthracycline (n. 40) A conventional post-induction chemotherapy including intermediate dosage Ara-C was administered to all responding patients. Univariate comparisons between patients in CR vs non CR were performed using chi-square analysis or Fisher's exact test for categorical variables and t-test for continuous variables. P values < 0.05 were considered statistically significant. Analyses were performed using SPSS. The prognostic impact of WT1 expression was evaluated using quartiles as cut off point and selecting the one with the lowest p value. The event free survival and OS were calculated using the Kaplan Meier method. Non CR after the first induction course, relapse and death due to any cause were considered events. OS and EFS duration were calculated from start of treatment. The impact of multiple predictor variables was assessed by multivariate analyses according to the Cox regression model for OS and EFS while for the evaluation of RC was used the Logistic regression model. Median age of patients was 59 years (range 17-81). Cytogenetic alterations were prognostically favorable in 3 patients and belonged to the intermediate prognostic group in 77 patients (normal karyotype in 75 patients and +8 in two). Nineteen patients had a poor prognosis cytogenetics. For statistical analyses we considered two karyotipic groups: unfavorable (19 patients) and not unfavorable (80 patients). CRs were 60/99 (60%), of which 40 in 51 patients aged 60 or less (78%) and 20 in 48 older than 60 years (41%). Twenty-six patients relapsed, 54 are alive, 45 have died, with a median follow up of 360 days (range 20-2300). In Table 1 are reported clinical indicators of outcome being patients grouped according to the percentile of WT1 expression with the lowest p value (75th). Statystical analysis showed that all WT1 quartiles were balanced for other prognostic factors, such as cytogenetics, BAALC expression, FLT3 and NPMA and B mutations, age, blast count and therapy. The lack of consense on the role of WT1 level at diagnosis in the prognostic stratification indicate that further clinical studies are required. The clear correlation between the level of WT1 transcript and the tumor burden explains why WT1 is used in the follow up of leukemic patients as universal marker of residual disease, also in patients with specific chimeric products. On the contrary, the biological explanation of the prognostic impact of WT1 transcript level at diagnosis remains uncertain. Over the years WT1 gene has been considered as an oncogene or a tumor suppressor gene. In our experience the protective influence of high WT1 expression cannot be explained with an association with good prognosis biological features (such as mut NPM and / or low BAALC). The positive prognostic value of high WT1 expression might be implicated either with WT1 antioncogenic function, or with the stimulating effect of WT1 oncogene on leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.Table 1WT1 <= 2400 N./N.pts (%)WT1 > 2400 N./N.pts (%)p univ,p multiv.*RR (95% CI)CR (all karyotypes)41/ 75 (54)19/24 (82)0,0260.063.364 (0.927-12.202)CR (int/good karyot.)36/59 (61)19/210.010,0276.649 (1.240-35.645)CR (denovo AML int kar)31/45 (69)14/15 (98)0.020,03412.557 (1.218-129.446)CR (denovo, N.K.)26/40 (65)15/16 (94)0.0250.0413.430 (1.111-162.318)EFS at 24 months (all karyotypes)8%6%0.0020.050.486 (0.235-1.007)EFS at 24 months (int / good karyot.)9%64%0.0010.0230.360 (0.150-0.866)EFS at 24 months (de novo, N.K.)5%70%0.0010.0070.227 (0.077-0.671)OS (all karyot)15%55%0,110,660.837 (0.371-1.890)OS (int/good kar.)18%63%0,050,180.507 (0.186-1.381)Table 1 legend: * for multivariate analysis age, karyotype, FLT3, NPM mutation, BAALC expression, denovo/secondary disease were considered. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effect of Isoniazid Preventive Therapy on the Incidence of Tuberculosis among Seropositive Children Attending HIV/AIDS Care in Two General Hospitals, Northwest Ethiopia, 2021

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Fassikaw Kebede ◽  
Birhanu Kebede ◽  
Tsehay Kebede ◽  
Melaku Agmasu
Keyword(s):  
Cox Regression ◽  
Data Entry ◽  
Concomitant Administration ◽  
Preventive Therapy ◽  
Northwest Ethiopia ◽  
Isoniazid Preventive Therapy ◽  
Categorical Variables ◽  
P Value ◽  
Human Immune Deficiency Virus

The human immune deficiency virus (HIV) is the strongest risk factor for the incidence of tuberculosis (TB) by way of reactivation of latent or new infection. The provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB. To date, there have been limited clinical data regarding the effectiveness of isoniazid preventive therapy (IPT) on TB incidence. This study aimed to assess the effect of isoniazid preventive therapy on the incidence of tuberculosis for seropositive children in Northwest Ethiopia. Methods. A facility-based retrospective follow-up was employed for reviewing 421 files from 1 January 2015 up to 30 December 2019. EpiData version 3.2 and Stata/14 software were used for data entry and analysis, respectively. Categorical variables at bivariable Cox regression were assessed for candidates transferred at P value <0.25 for multivariable Cox regression to claiming predictors associated with TB incidence rate at 95% CI at P < 0.005 . Result. The overall incidence of TB was found to be 4.99 cases per 100 person-years at 95% CI (3.89–6.53). Missed IPT (AHR = 7.45, 95% CI: 2.96, 18.74, P < 0.001 ), missed cotrimoxazole preventive therapy (CPT) (AHR = 2.4, 95% CI: 1.84–4.74, P < 0.022 ), age ≥ 11 years (AHR = 4.2, 95% CI: 1.04–7.03, P < 0.048 ), MUAC ≤ 11.5 cm (AHR = 4.36, 95% CI: 1.97–9.97, P < 0.001 ), WHO stages III and IV (AHR = 2.04, 95% CI: 1.12–3.74, P < 0.022 ), and CD4 count ≤100 cells/μl (AHR = 3.96, 95% CI: 1.52–10.34, P < 0.005 ) were significantly associated with TB incidence. Conclusion. Concomitant administration of ART with IPT had demoted more than ninety-six percent of new TB incidences for this report. Undertaking in-depth TB screening and frequent follow-up among all these children is critical in order to prevent and control tuberculosis.

scholarly journals Other Cancers in Long-Term Survivors of Chronic Lymphocytic Leukemia: Incidence and Prognostic Relevance

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3323-3323 ◽  
Author(s):  
Lorenzo Falchi ◽  
Michael Keating ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
Kplola Y Elhor Gbito ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Observation Time ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
Prognostic Impact ◽  
Long Term Survivors

Abstract Introduction. The clinical course of chronic lymphocytic leukemia (CLL) is mostly indolent. About one third of the patients are managed with lifelong watch-and-wait (WW) and those who receive therapy often achieve a durable remission. As a result, the majority of patients with CLL will live with their disease for long periods of time, and be exposed to several complications, including the occurrence of other cancers (OC). Patients with CLL may have an increased incidence in OC. Published reports indicate an incidence of 3-27%, mostly in treated patients, however, very little is known on OC in patients with CLL not requiring therapy. Furthermore, observation time in published studies is limited to <5 years, and the incidence of OC in patients followed for longer than 10 years is unknown. We, therefore, studied the incidence and prognostic impact of OC in treatment-naïve patients with CLL followed for ≥10 years. Methods. We reviewed our database and identified all patients with CLL untreated at the time of referral. We selected long-term survivors (LTS), defined as patients with a follow-up ≥10 years, and analyzed the incidence and prognostic impact of OC in this population. Non-melanoma skin cancers were excluded since these were diagnosed and treated promptly in virtually all cases and felt not to have prognostic impact. Standardized incidence ratios (SIR) were calculated for OC occurring after the diagnosis of CLL that were reportable to the Surveillance, Epidemiology and End Results program.The estimated overall survival (OS) according to the presence of OC was plotted considering OC as a time-dependent covariate. Results. We identified 797 LTS of CLL seen at our institution between 1957 and 2003. Median age was 56 years (24-88). 57% of patients were males. Median follow-up for the entire population is 154 months (120-485). We recorded 383 OC in 286 (36%) patients. 76/286 (26%) patients had >1 OC (62 had 2 OC, 10 had 3, 2 had 4, 1 had 5 and 1 had 6).The firstOC preceded or was diagnosed concomitantly with CLL in 100 patients (35%), while in the remaining 186 (65%) it occurred later during the course of the disease. 570 patients (71%) required treatment for CLL. Median time to treatment was 18 months (0-454). In treated patients, the cumulative frequency of OC was 205/570 (36%) and in WW patients 81/227 (36%). The SIR for all OC was 1.2 (p = .034). Males and patients younger than 60 years had a significantly higher incidence of OC (SIR 1.31 and 1.27, respectively). Among OC types, secondary leukemia, melanoma and head and neck cancers had the highest observed-to-expected ratio. Surprisingly, lung, digestive tract, and bladder cancer had a lower-than-expected incidence (table). 474 patients (59%) are alive. 222/570 (39%) treated patients and 101/227 (44%) WW patients have died. The median OS was longer in patients without OC (279 months) vs. those with OC (189 months). Independent predictors of shorter survival in multivariate analysis included higher creatinine, the presence of OC, and older age. Discussion. This is the first study to address the incidence of OC in LTS of CLL, including WW patients. In our population, the frequency of OC is similar in treated and WW patients. Although the incidence of OC in LTS of CLL is higher compared to matched general population, the incidence of lung, digestive and bladder cancer is lower than expected. Reasons of this finding remain to be identified.The occurrence of OC is an independent predictor of shorter survival, thus constituting a relevant competing risk of mortality in LTS of CLL. Variable Observed Expected Person-years SIR (O/E) 95% CI for O/E P -value Overall 148 123.34 10956 1.20 1.01 – 1.40 0.034 Male 96 73.4 5885 1.31 1.06 – 1.58 0.013 Female 52 49.93 5071 1.04 0.78 – 1.36 0.67 Age ≥60 years 60 54.33 3416 1.10 0.84 – 1.42 0.44 Age <60 years 88 69.02 7540 1.27 1.02 – 1.57 0.027 OC type Prostate 28 25.92 11809 1.08 0.72 – 1.56 0.64 Lung 20 29.08 11942 0.69 0.42 – 1.06 0.04 Breast 19 18.60 11855 1.02 0.62 – 1.59 0.96 Melanoma 16 4.23 11926 3.78 2.16 – 6.14 0.00 Leukemia 15 4.27 12009 3.51 1.96 – 5.79 0.00 Non-Hodgkin lymphoma 6 6.38 11996 0.94 0.34 – 2.05 1.00 Digestive 16 40.4 11937 0.40 0.23 – 0.64 0.00 Colon 8 19.42 11972 0.41 0.18 – 0.81 0.006 Pancreas 2 4.83 12024 0.41 0.05 – 1.49 0.18 Rectal 3 8.69 12011 0.34 0.07 – 1.00 0.05 Bladder 3 11.18 11993 0.27 0.05 – 0.78 0.009 Multiple Myeloma 2 1.98 12012 1.01 0.12 – 3.64 1.00 Lip 3 0.02 12015 150 31.00 – 438.5 0.00 Salivary gland 2 0.03 12026 66.66 8.00 – 240.06 0.00 Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of the cardio-hepatic syndrome on outcomes after transcatheter mitral valve edge-to-edge repair

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Stolz ◽  
M Orban ◽  
N Karam ◽  
E Lubos ◽  
M Wild ◽  
...  
Keyword(s):  
Liver Function ◽  
Cox Regression ◽  
Cox Model ◽  
Hepatic Function ◽  
Gamma Glutamyl Transferase ◽  
Prognostic Impact ◽  
Laboratory Parameters ◽  
Glutamyl Transferase ◽  
The Impact

Abstract Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p&lt;0.01). In a multivariate Cox regression model, CHS was identified as a strong and independent predictor of increased two-year mortality (hazard ratio 1.49, p=0.03). In patients with successful MR reduction ≤2+ (90.7% of patients), parameters of hepatic function significantly improved from baseline to follow-up (−0.2 mg/dl for bilirubin; −21 U/l for GGT, respectively, p&lt;0.01), while they did not in case of residual postprocedural MR &gt;2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. FUNDunding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER

Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) Monitoring of Minimal Residual Disease (MRD) in Core Binding Factor Acute Myeloid Leukaemia (CBF AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2296-2296
Author(s):  
Steven W. Lane ◽  
Russell Saal ◽  
Peter Mollee ◽  
Andrew Grigg ◽  
Kerry Taylor ◽  
...  
Keyword(s):  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
P Value ◽  
Sample Number ◽  
Long Term Outcome ◽  
Clinical Prognosis ◽  
Transcript Levels ◽  
Post Induction ◽  
The Impact

Abstract Background: CBF AML, with t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) and the associated fusion proteins AML1/ETO or CBFβ/MYH11, has a favourable clinical prognosis although significant numbers of patients still relapse. We examined the prognostic utility of MRD monitoring by RQ-PCR and propose a simple model for prediction of impending haematological relapse. Methods: Patients with CBF AML had samples collected at diagnosis, after induction and consolidation chemotherapy and at routine regular intervals thereafter. RQ-PCR, using the Applied Biosystems 7700 Sequence Detection System, was performed in triplicate and the final result was calculated by averaging 3 values, expressed relative to PGK levels. Stratified Cox regression was used to assess the impact of predictor variables (diagnostic, post-induction, post-consolidation RQ-PCR levels and presence of a 1 log10 increase in sequential RQ-PCR levels) on leukaemia-free survival (LFS). Results: Of 46 patients identified with CBF AML, 29 had diagnostic, regular longitudinal samples and clinical follow up allowing further evaluation; 12 AML1-ETO and 17 CBFβ-MYH11. The median age was 39 years (range 7–68) with 52% male. Median follow up was 34 months (range 1–106) and median sample number was 6 (2–15). Twelve relapses occurred at a median of 11 months (range 4–17) from diagnosis. There were significant differences between transcript levels at diagnosis (median 1.9), post-induction (8.96*10−04), post-consolidation (5.01*10−05), in remission (1*10−06) or relapse (0.15) (p=0.01). Diagnostic, post-induction and post-consolidation RQ-PCR levels did not predict outcome. A log10 rise in a remission bone marrow sample correlated with adverse LFS and imminent risk of haematological relapse (HR 8.6). Relapses occurred a median of 60 days (range 45–272) after a log10 rise. RQ-PCR levels Hazard Ratio (HR) LFS 95% CI P-value Diagnosis 0.22 0.02–2.9 0.25 Post-induction 1.3 0.8–2.1 0.36 Post-consolidation 0.8 0.5–1.2 0.27 1 log10 increase 8.6 1.8–42 0.008 Conclusions: A 1 log10 rise in transcript levels was a highly significant predictor of haematological relapse. Transcript levels at early post-treatment time points did not predict long term outcome, cautioning against de-escalation protocols based on these results. Prospective identification of high risk patients will enable clinical trials to address the efficacy of treatment initiated at molecular progression.

The Proportion of Clonal Plasma Cells In the Bone Marrow Analyzed by FISH Rather Than Single Chromosomal Abnormalities Predict Progression From Smoldering to Symptomatic Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2950-2950
Author(s):  
Kai Neben ◽  
Anna Jauch ◽  
Dirk Hose ◽  
Christiane Heiss ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosomal Aberration ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Entire Group ◽  
P Value ◽  
Fish Analysis ◽  
Prognostic Impact

Abstract Abstract 2950 Smoldering MM (sMM) is a plasma cell disorder defined by the presence of ≥10% plasma cells in bone marrow and/or a monoclonal protein level of ≥3 g/dl in serum without organ damage. The aim of this retrospective study was to analyze whether genomic abnormalities confer prognostic information in patients with sMM who are at high risk of progression into symptomatic MM. By using fluorescent in situ hybridization (FISH), we analyzed the prognostic value of 14 chromosomal abnormalities and hyper-/non-hyperdiploidy (HD and NHD, respectively) in a series of sMM-patients (n=200). In addition, the most frequent chromosomal aberration was used to determine the percentage of clonal plasma cells (cPC) in the bone marrow. Interphase-FISH-analysis on CD138-enriched plasma cells detected gains of chromosomes 1q21 (31%), 5p15/5q35 (35%), 9q34 (45%), 11q23 (41%), 15q22 (40%), and 19q13 (41%), as well as deletions of chromosomes 8p21 (9%), 13q14 (37%) and 17p13 (7%). Furthermore, the IgH-translocations t(14;16), t(4;14), t(11;14) and IgH-translocations with unknown translocation partner were observed in a frequency of 5%, 10%, 24% and 22%, respectively. The median percentage of cPC was 85.5 (IQR: 62 – 95). For the entire group, the median follow-up time was 27.2 months (range, 18.2 – 33.5). We analyzed the prognostic impact of each chromosomal aberration on time to progression (TTP). Of all chromosomal abnormalities analyzed, only del(8p21) and the percentage of cPC showed a significant impact on TTP. The TTP at 3 years for patients with del(8p21) was 53% versus 73% for those without (p=0.01). An incremental increase of cPC in the bone marrow by 10% was associated with an elevated relative risk to develop a symptomatic MM of 33% (p<0.001). After adjustment of p-values for multiple testing, only the percentage of cPC showed a statistically significant impact on TTP (p=0.02). Our results show that FISH-analysis on CD138-enriched plasma cells is a useful technique in the study of sMM, because it allows myelomatous plasma cells to be discriminated from their normal counterparts. In addition, our findings suggest that the proportion of cPC (analyzed by FISH) rather than single chromosomal abnormalities predict progression from sMM to symptomatic MM. FISH-based information can be obtained easily at the time of diagnosis, which would help to establish an individually adapted follow-up strategy. Aberration yes vs. no N Incidence 3-yr TTP (present vs. absent) Hazard ratio Wald test p-value adjusted del(8p21) 190 9% 53% vs. 73% 2.59 0.1 del(13q14) 200 37% 61% vs. 79% 1.77 0.8 del(17p13) 198 7% 56% vs. 72% 1.95 1 t (4;14) 198 10% 52% vs. 73% 1.68 1 t (11;14) 198 24% 77% vs. 69% 0.51 1 t (14;16) 197 5% 57% vs. 71% 1.59 1 +1q21 197 31% 60% vs. 75% 1.71 1 HD vs. NHD 197 40% 65% vs. 74% 1.67 1 10% increase of cPC 200 – – 1.33 0.02 cPC >95 vs. ≤95% 200 23% vs. 77% 46% vs. 80% 3.84 <0.001 Disclosures: No relevant conflicts of interest to declare.

Gene-Expression for Prediction of Disease Progression Following Initial Management of Follicular Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4804-4804
Author(s):  
Etienne Mahe ◽  
Ariz Akhter ◽  
Danielle H. Oh ◽  
Fahad Farooq ◽  
Meer-Taher Shabani-Rad ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Regression Model ◽  
Disease Progression ◽  
Cox Regression ◽  
Tumor Grade ◽  
Age At Diagnosis ◽  
P Value ◽  
Cox Regression Model ◽  
Cox Regression Analysis

Abstract Introduction Patients with advanced staged Follicular Lymphoma (FL) are initially managed with either immediate chemoimmunotherapy (CI) or "watchful waiting" (WW) depending on clinical symptoms, tumor burden, and organ compromise. Clinicians currently predict time to progression (TTP) using the Follicular Lymphoma International Prognostic Index (FLIPI) score. Well-defined & validated molecular techniques capable of additional predictive power are lacking, however. We hypothesized that gene-expression (GE) data, employing an evidence-based feature set, might assist in the upfront stratification of FL patients. Objectives 1 Identify genes whose GE has previously been identified as relevant to FL 2 Perform GE testing on an series of FL cases, classified by upfront intervention, using this custom gene feature set 3 Identify the gene(s) most strongly predictive of disease progression in each of the clinical classes (i.e. CI vs. WW) 4 Compare the performance of GE data to other prognostic parameters Methods We performed a search of MEDLINE-indexed studies reporting FL GE results. We input all available appertaining data into NVIVO (v10), in which a computer-assisted search for GE features was performed. This list, after refinement, formed the basis of a custom NanoString codeset. We used the MD Anderson Microarray Sample Size Calculator for sample size estimation and retrieved FL cases from our regional archives; those cases with sufficient tissue were organized by upfront treatment approach and available clinical data recorded (age at diagnosis, sex, stage, grade, FLIPI scores & TTP). TTP was defined as time in months either to diagnosed disease progression or, in the WW group, first CI-based treatment. After pathology review, RNA was isolated using standard protocols. GE data was analyzed using gene-specific receiver-operating characteristic analysis, ranking performed according to the area-under-the-curve (MATLAB v 8.3.0.532). Validation against TTP using Cox-regression was then performed (SPSS v22); p < 0.05 was considered significant. Results Our MEDLINE search yielded 713 publications; after refinement, our NVIVO analysis suggested 282 valid gene features. Review of local FL cases accessioned between 2004 & 2012 was performed; this period ensured uniform follow-up and CI treatment strategies for all FL patients. Patients were classified as WW (68 patients) & CI (98 patients), and then sub-classified as WW1 (WW without need for CI over the follow-up interval; 23 patients) and WW2 (WW requiring CI in the follow-up interval; 45 patients) and CI1 (CI without disease progression over the follow-up interval; 61 patients) and CI2 (CI with disease progression; 37 patients). Median follow-up time was 60 months in the WW group and 56 months in the CI group (Mann-Whitney p = 0.177). With the exception of FLIPI score in the WW class (higher on average in the WW2 sub-class), no other clinical factor differed significantly between the sub-classes. GE analyses suggested that ACTB in the WW group and MEK1 in the CI group might be most predictive of TTP. Table 1. TTP results by Cox-regression analysis for the WW group WW Variable Cox-Regression Model Co-efficient p-value Cox-Regression Model Linear Co-efficient 95% CI Age at diagnosis 0.56 0.98-1.04 Sex 0.34 0.67-3.19 Tumor Grade 0.41 0.40-9.48 Tumor Stage 0.54 0.69-2.04 FLIPI Score 0.06 0.97-3.6 ACTB Expression 0.006 1.4-7.74 Table 2. TTP results by cox-regression analysis for the CI group CI Variable Cox-Regression Model Co-efficient p-value Cox-Regression Model Linear Co-efficient 95% CI Age at diagnosis 0.34 0.99-1.04 Sex 0.96 0.48-2.16 Tumor Grade 0.92 0.43-2.13 Tumor Stage 0.17 0.874-2.11 FLIPI Score 0.4 0.47-1.35 MEK1 Expression 0.011 0.19-0.81 Conclusions To our knowledge, we have performed the first GE analysis of FL cases classified by intervention, and have identified GE features predictive of disease progression or requirement of intervention (as in the WW group). In the CI group, identification of MEK1 as a major prognostic player echoes previous work studying the MAP-kinase pathway in FL. In the WW group, however, identification of ACTB as a potential prognostic player is a novel observation requiring validation, especially since this gene is ubiquitously expressed across multiple cell types. Figure 1. WW TTP, stratified by ACTB expression Figure 1. WW TTP, stratified by ACTB expression Figure 2. CI TTP, stratified by MEK1 expression Figure 2. CI TTP, stratified by MEK1 expression Disclosures No relevant conflicts of interest to declare.

scholarly journals First and second waves among hospitalised patients with COVID-19 with severe pneumonia: a comparison of 28-day mortality over the 1-year pandemic in a tertiary university hospital in Italy

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e054069
Author(s):  
Marianna Meschiari ◽  
Alessandro Cozzi-Lepri ◽  
Roberto Tonelli ◽  
Erica Bacca ◽  
Marianna Menozzi ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Regression Model ◽  
Cox Regression ◽  
Severe Pneumonia ◽  
University Hospital ◽  
P Value ◽  
Cox Regression Model ◽  
Hospitalised Patients ◽  
The Impact ◽  
Second Wave

ObjectiveThe first COVID-19–19 epidemic wave was over the period of February–May 2020. Since 1 October 2020, Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients.DesignObservational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of HRs with 95% CIs. A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed.SettingUniversity Hospital of Modena, Italy. Patients admitted to the hospital for severe COVID-19 pneumonia during the first (22 February–31 May 2020) and second (1 October–31 December 2020) waves were included.ResultsDuring the two study periods, a total of 1472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1023 during the second. Median age was 70 years (IQR 56–80), 37% women, 49% with PaO2/FiO2 <250 mm Hg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI 16.3 to 23.7) during the first wave vs 14.2% (95% CI 12.0 to 16.3) in the second (log-rank test p value=0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the second wave (aHR=0.64, 95% CI 0.45 to 0.90, p value=0.01).ConclusionsIn our hospitalised patients with COVID-19 with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared with the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.

scholarly journals Long-term Prognostic Value of Homocysteine in Patients with Acute Coronary Syndrome Complicated with Hypertension: A Multicenter Retrospective Study

2021 ◽  
Author(s):  
Qiang Chen ◽  
Xunshi Ding ◽  
Caiyan Cui ◽  
Tao Ye ◽  
Lin Cai
Keyword(s):  
Acute Coronary Syndrome ◽  
Regression Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
P Value ◽  
Cox Regression Analysis ◽  
Coronary Syndrome ◽  
Kaplan Meier

Abstract Background and aims: This study investigates the long-term prognostic value of homocysteine in patients with acute coronary syndrome complicated with hypertension. Methods:The current work is a multicenter, retrospective, observational cohort study. We consecutively enrolled 1288 ACS patients hospitalized in 11 general hospitals in Chengdu, China, from June 2015 to December 2019. The patients were divided into hypertension and non-hypertension groups, and each was further classified into hyperhomocysteinemia (H-Hcy) and normal homocysteinemia (N-Hcy) groups according to the cut-off value of homocysteine predicting long-term mortality during follow-up. In both groups, we used Kaplan-Meier and multivariate Cox regression analysis to assess the relationship between homocysteine and long-term prognosis. Results: The median follow-up time was 18 months (range: 13.83-22.37). During this period, 78 (6.05%) death cases were recorded. The hypertension was further divided into H-Hcy (n=245) and N-Hcy (n=543), with an optimal cut-off value of 16.81 µmol/L. Similarly, non-hypertension was further divided into H-Hcy (n=200) and N-Hcy (n=300), with an optimal cut-off value of 14 µmol/L. Kaplan-Meier survival curves revealed that H-Hcy had a significantly lower survival probability than N-Hcy, both in hypertension and non-hypertension (P-value<0.01). After adjusting for confounding factors, multivariate Cox regression analysis revealed that H-Hcy (HR=2.1923, 95% CI: 1.213-3.9625, P＜0.01) was an independent predictor of long-term all-cause death in ACS with hypertension, but not in non-hypertension.Conclusion: Elevated homocysteine level predicts risk of all-cause mortality in ACS with hypertension, but not in those without hypertension. it should be considered when determining risk stratification for ACS, particularly those complicating hypertension.

A Study on the Prognosis of Patients Relapsing after Autologous Stem Cell Transplantation (auto-SCT) for Follicular Lymphoma (FL): The Impact of Remission Duration.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3064-3064
Author(s):  
Julia Stumm ◽  
Jens Dreyhaupt ◽  
Martin Kornacker ◽  
Manfred Hensel ◽  
Michael Kneba ◽  
...  
Keyword(s):  
Cox Regression ◽  
Treatment Time ◽  
Salvage Treatment ◽  
Prognostic Impact ◽  
Post Transplant ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Time To Relapse ◽  
The Impact

Abstract Although auto-SCT has been in use for treatment of advanced FL since many years, little is known about the course of those who relapse after this procedure. Because these patients may be candidates for aggressive salvage approaches, we sought to study the outcome of patients with FL relapsing after auto-SCT with particular focus on factors predicting for survival. Methods: Relapse cases were identified retrospectively from 244 patients autografted for FL between August 1990 and November 2002 in 3 institutions. Overall survival after relapse (OS) was calculated according to Kaplan-Meier and analyzed for the prognostic impact of pre-relapse variables as well as of post-relapse salvage treatment by univariate log rank comparisons and Cox regression analyses. Results: With a median follow-up of 88 (5–186) months post auto-SCT, 104 relapses occurred, corresponding to a 10-year relapse probability of 0.47 (95%CI 0.4–0.53). Median age of relapsed patients was 48 (22–65) years. FLIPI score at diagnosis was low in 18%, intermediate in 58%, and high in 24%. In 51%, auto-SCT had been given as part of first-line treatment, and 45% had been in complete remission at auto-SCT. Myeloablation included total body irradiation (TBI) in 57% of the cases. Median time from auto-SCT to relapse was 19 (2–128) months, with only 2 relapses occurring later than 6 years post transplant. Transformed FL was present in 14% of those 87 patients who had relapse histology available. Rituximab-containing salvage therapy was given to 50% of the patients after relapse. With 45 (1–139) months of follow-up, median OS after relapse was 100 months. Log rank comparisons identified auto-SCT as part of salvage treatment, time to relapse <12 months, and salvage without rituximab as factors adversely influencing OS, while all other variables listed above had no impact. Cox analysis considering sex, age, salvage auto-SCT, TBI, time to relapse, and rituximab salvage confirmed a possible adverse impact of time to relapse <12 months (hazard ratio 2.58 (95%CI 0.99–6.82); p 0.055) but none of the other covariates on OS. Conclusions: The prognosis of patients relapsing after auto-SCT for FL is surprisingly good. However, those whose disease recurs within the first post-transplant year tend to have a dismal outcome and might benefit from experimental salvage approaches, such as allogeneic SCT.

High BAALC Expression in Cytogenetically Normal Acute Myeloid Leukemia Strongly Correlates with Adverse Markers Such As RUNX1mut, MLL-PTD and FLT3-ITD and Is Useful for Disease Monitoring

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1376-1376
Author(s):  
Simone Weber ◽  
Tamara Alpermann ◽  
Christiane Eder ◽  
Frank Dicker ◽  
Sabine Jeromin ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Clinical Outcome ◽  
Mrna Expression ◽  
Cox Regression ◽  
Disease Monitoring ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 1376 Introduction: BAALC expression is thoroughly explored in cytogenetically normal AML (CN-AML) and has been shown to be associated with an adverse outcome. Nevertheless, its prognostic importance in relation to other molecular markers and its relevance for detection of minimal residual disease (MRD) remains to be defined. The objective of this study was to evaluate the prognostic impact of BAALC expression on clinical outcome in the context of other relevant molecular prognosticators and to examine its utility as a marker for detection of MRD in CN-AML. Patients: BAALC mRNA expression was analyzed in a cohort of 332 patients with de novo CN-AML. The cohort was composed of 169 females (50.9%) and 163 males (49.1%). Age ranged from 18.3 to 64.8 years (median: 52.9). Data on other molecular markers was available in: FLT3-ITD: n=332, NPM1: n=332, RUNX1: n=330, CEBPA: n=332, MLL-PTD: n=332, ASXL1: n=330, FLT3-TKD: n=331, IDH1G105: n=229, IDH1R132: n=253, IDH2: n=232, NRAS: n=254, WT1 mut: n=247, TET2: n=74 and TP53: n=182. In addition, BAALC expression was assessed in 25 follow-up samples of 8 patients in comparison with an established MRD marker. Methods: To assess BAALC mRNA expression levels RQ-PCR was performed by the use of the Applied Biosystems 7500 Fast Real Time PCR System. BAALC expression was normalized against the expression of the control gene ABL1. The median ratio BAALC/ABL1 was used to separate low from high BAALC expressers. Expression data of diagnostic samples was correlated to clinical outcomes and to the presence of molecular mutations. BAALC expression ratios of follow-up samples were also correlated to the status of other molecular markers available in the same patients. Results: 1) Evaluation of prognostic relevance: Expression ratios of BAALC/ABL1 represented a continuum ranging from 0.001 to 80.199 (median: 0.321). In agreement with previous studies, patients with high BAALC expression had shorter overall survival (OS at 3 years: 51.4% vs 73.0%, p=0.046) and event free survival (EFS at 3 years: 38.5% vs 50.6%, p=0.021) as compared to low BAALC expressers. Though, associations of BAALC expression to other molecular markers were found. In high BAALC expressers, as compared to low BAALC expressers, the following mutations were more frequent: RUNX1 mut (32/164, 19.5% vs 2/166, 1.2%, p<0.001), MLL-PTD (22/166, 13.3% vs 5/166, 3.0%, p=0.001) and FLT3-ITDmut/wt ratio>0.5 (51/166, 30.7% vs 24/166, 14.5%, p=0.001), whereas NPM1 mut were less frequent (72/166, 43.3% vs 138/166, 83.1%, p<0.001). In univariable Cox regression analyses shorter OS and EFS was associated with higher age, higher WBC count, high BAALC expression and the presence of at least one of the established adverse markers RUNX1 mut, MLL-PTD, or FLT3-ITDmut/wt ratio>0.5 grouped together as one parameter (OS, p<0.001, <0.001, 0.0048, <0.001, respectively; EFS, p=0.002, <0.001, 0.022, <0.001, respectively). In multivariable models, BAALC expression had an independent impact on EFS (p=0.042) but not on OS. Further, Kaplan Meier analysis within the subgroup with adverse markers (RUNX1 mut, MLL-PTD, or FLT3-ITDmut/wt ratio>0.5, n=98) revealed no additional impact of BAALC expression on OS or EFS. Also within the prognostically favorable subgroup with NPM1 mut/FLT3-ITDmut/wt ratio<0.5 high BAALC expression had no impact on OS or EFS. 2) Validation as follow-up marker: To evaluate the impact of BAALC expression for disease monitoring during follow-up, the BAALC/ABL1 ratio of high BAALC expressers was compared to the %MLL-PTD/ABL1 or %RUNX1 mut levels in patients who had at least one of these aberrations in parallel. In total, 33 diagnostic and follow-up samples of 8 patients were analyzed. Comparison of BAALC/ABL1 ratios to mutational status of MLL-PTD and/or RUNX1 revealed a significant correlation (r=0.577, p<0.001). Additionally, in one case with paired samples at diagnosis and relapse, BAALC expression levels at diagnosis and at relapse were in the same range (BAALC/ABL1: 10.870 vs 17.600). Conclusion: 1) BAALC expression in CN-AML predicts an adverse clinical outcome, but is associated with other well established prognostic markers. Thus, in our study BAALC expression had no independent prognostic impact on OS when analyzed together with RUNX1, MLL-PTD, FLT3-ITD and NPM1. 2) Correlation of BAALC expression with MLL-PTD and RUNX1 during follow up indicates that BAALC expression is a potential target for MRD monitoring. Disclosures: Weber: MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Dicker:MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Fasan:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership.

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