Can Addition of GM-CSF in Adult Haplo-Identical Transplant Who Cannot Benefit from NK Alloreactivity Improve the Relapse Rate of Advanced Leukemia: A 3 Step Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4975-4975
Author(s):  
Philippe Lewalle ◽  
Alain Delforge ◽  
Berengere Nowak ◽  
Virginie Misplon ◽  
Laurence Lagneaux ◽  
...  

Abstract Haplo-identical transplant is now established as a procedure of choice for patients who lack a compatible donor. It might even be the best choice for AML, provided there is a GvH NK alloreactivity. However, patients are still referred too late, heavily pre-treated, at very advanced stages. We initiated a three-step phase I study trying improve transplant related mortality, relapse rate and immunity: (1): G-CSF + DLI, (2): GM-CSF + DLI, (3): patient and disease adapted strategy. Thirty-four consecutive leukemia patients, aged 18–55, were investigated (20 very poor risk, 11 poor risk and 3 better risk). GvH type NK alloreactivity was chosen when possible (19/34) and balanced across the 3 groups. In the first 9 patients, G-CSF was used pot-transplant and prophylactic DLI were given at month 1, 2 and 3. The use of G-CSF and 1 to 3 DLI (104 CD3/kg) was found safe. It resulted in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a protective GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (104 CD3/kg) at day 30 unless aGVHD (3 pts). The comparison between the 2 first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD:0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD grade 2 or more: 9/12; price to pay: GVHD resulting in 5 deaths in total. Median time to relapse in the 21 first patients was 6 months (range 4 to 9). Step 3 (14 patients) consists of a patient adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK alloreactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mcg) is given from day 5 to day 9. The follow-up of these 14 patients, although promising (2 relapses), is currently short (median 5 months), compared to the median of relapse in the 2 first groups (6 months) but will be updated for the meeting (10 months and 17 patients). Overall, TRM at day 100 is 3/29, reflecting the good tolerance of the conditioning in a heavily pre-treated population (median age : 43). Overall NR-mortality at one year is 8/26, but was greater in the GM-CSF + DLI group, reflecting the impact of severe aGVHD. In the current group, its is 2/14 at 3 months. We conclude that the third strategy might improve the outcome and the relapse rate without exposing patients to unnecessary severe GVHD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2912-2912
Author(s):  
Philippe Lewalle ◽  
Alain Delforge ◽  
Berengere Nowak ◽  
Virginie Misplon ◽  
Jalil Bennani ◽  
...  

Abstract Haplo-identical transplant is now established as a procedure of choice for patients who lack a compatible donor. It might even be the best choice for AML, provided there is a GvH NK allo-reactivity. However, patients are still referred too late, heavily pre-treated, at very advanced stages. We initiated a three-step phase I study trying improve transplant related mortality, relapse rate and immunity: : G-CSF + DLI, : GM-CSF + DLI, : patient and disease adapted strategy. Thirty-six consecutive leukemia patients, aged 18–55, were investigated (20 very poor risk, 12 poor risk and 4 better risk). GvH type NK alloreactivity was chosen when possible (21/36) and balanced across the 3 groups. In the first 9 patients, G-CSF was used pot-transplant and prophylactic DLI were given at month 1, 2 and 3. The use of G-CSF and 1 to 3 DLI (10exp4 CD3/kg) was found safe. It resulted in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a protective GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (104 CD3/kg) at day 30 unless aGVHD (3 pts). The comparison between the 2 first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD:0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD grade 2 or more: 9/12; price to pay: GVHD resulting in 5 deaths in total. Median time to relapse in the 21 first patients was 6 months range (4 – 9). Step 3 (17 patients) consists of a patient adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK allo-reactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mcg) is given from day 5 to day 9. The follow-up of patients alive in CCR (12), although promising (3 relapses), is currently short (median 8 months), compared to the median of relapse in the 2 first groups (6 months). Overall, TRM at day 100 is 2/29, reflecting the good tolerance of the conditioning in a heavily pre-treated population (median age: 43). Overall relapse rate for all patients treated with GM-CSF, without the benefit of NK-alloreactivity, is 6/16 (median FU: 15 months). We conclude that the third strategy might improve the outcome and the relapse rate without exposing patients to unnecessary severe GVHD. These data will be updated with 6 months more follow-up and 3 more patients.


2011 ◽  
pp. 13-19
Author(s):  
Nhu Minh Hang Tran ◽  
Huu Cat Nguyen ◽  
Dang Doanh Nguyen ◽  
Van Luong Ngo ◽  
Vu Hoang Nguyen ◽  
...  

Objectives: To determine factors impact on the relapse in depressed patients treated with Cognitive Behavioral Therapy (CBT) during one year follow-up. Materials and Methods: 80 depressed patients divided into two groups, group 1: included 40 patients treated with CBT; group 2: 40 patients on amitriptyline. Non-randomized controlled clinical trial, opened, longiditual and prospective research. Results and Conclusions: relapse rate after CBT during 1 year follow-up is 10% (compared to 25% in control group), related factors to relapse rate in depression after CBT are age and education. Shared predictors between 2 groups are severity and recurrence of depression. Key words: Depression, relapse, Cognitive Behavioral Therapy (CBT)


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Benito Gonzalez ◽  
X Freixa ◽  
C Godino ◽  
M Taramasso ◽  
R Estevez-Loureiro ◽  
...  

Abstract Background Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction, functional mitral regurgitation grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results 93 patients (68.2±10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-months follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0–17.8 vs 2.7–13.5, p=0.002), sustained VT or ventricular fibrillation (0.9–2.5 vs 0.5–2.9, p=0.012) and ICD antitachycardia therapies (2.5–12.0 vs 0.9–5.0, p=0.033) were observed. Conclusion PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort. Proportion of patients who presented ven Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 689.1-690
Author(s):  
S. Monti ◽  
L. Dagna ◽  
C. Campochiaro ◽  
A. Tomelleri ◽  
G. Zanframundo ◽  
...  

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p<0.001), but lower rates of general symptoms (56% vs 70% vs 77%; p<0.001). Large-vessel (LV)-GCA was less frequent in the older group (18% vs 22% vs 43%; p<0.001). At least one relapse occurred in 47% of patients. Median time to relapse was 12 months (IQR 6;23). Age did not influence the rate of relapses [18 per 100 persons/years (95%CI 15;21) vs 19 (95% CI 17;22) vs 19 (95%CI 17;22)], nor the time to first relapse (Figure 1). LV-GCA, presentation with significantly elevated c-reactive protein (> 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared


Vascular ◽  
2020 ◽  
pp. 170853812098369
Author(s):  
Stefano Fazzini ◽  
Giovanni Torsello ◽  
Martin Austermann ◽  
Efthymios Beropoulis ◽  
Roberta Munaò ◽  
...  

Objectives The results of branched endovascular repair of thoracoabdominal aneurysms are mainly dependent on durability of the graft used. The purpose of this study was to evaluate postoperative aortic main body and bridging stent-graft remodeling, and their impact on bridging stent-graft instability at one year. Methods Computed tomoangiographies of 43 patients (43 aortic main body mated with 171 bridging stent-grafts) were analyzed before and after branched endovascular repair as well as after a follow-up of 12 months. Primary endpoint was aortic main body remodeling (migration >5 mm, shortening >5 mm, scoliosis >5° or lordosis >5°). Shortening was defined as a reduced length in the long axis, scoliosis as left-right curvature, and lordosis as antero-posterior curvature. Aortic main body remodeling, aneurysm sac changes, and bridging stent-graft tortuosity were evaluated to study their correlations and the impact on the bridging stent-graft instability. Results At 12 months, aortic main body remodeling was observed in 72% of the cases, migration in 39.5% (mean 5.21 mm), shortening in 41.9% (mean 5.79 mm), scoliosis in 58.1%, (mean 10.10°), lordosis in 44.2% (mean 5.78°). Migration, shortening, and scoliosis were more frequent in patients with larger aneurysms ( p = .005), while scoliosis was significantly more frequent in type II thoracoabdominal aneurysm ( p = .019). Aortic main body remodeling was significantly associated to bridging stent-graft remodeling (r: 0.3–0.48). The bridging stent-graft instability rate was 9.3%. Despite a trend toward significance ( p = .07), none of the evaluated aortic main body and bridging stent-graft changes were associated with bridging stent-graft instability at 12 months. Conclusions Aortic main body remodeling is frequent especially in large and extended thoracoabdominal aneurysm aneurysms. Aortic main body and bridging stent-graft remodeling was significantly correlated. While these geometric changes had no significant impact on bridging stent-graft instability at one year, a close long-term follow-up after branched endovascular repair could predict bridging stent-graft failures.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nadia Abdelaaty Abdelkader ◽  
Amira Mahmoud AlBalakosy ◽  
Ahmed Fouad Helmy Sherief ◽  
Mohamed Soliman Gado

Abstract Background Hepatitis C virus (HCV) infection affects approximately 170 million people worldwide, causing liver cirrhosis and hepatocellular carcinoma (HCC) and leading to liver transplantation and ultimately death. Accurate evaluation of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in noninvasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with DAAs. Objectives The aim beyond this study is to evaluate the changes in liver stiffness in hepatitis C Egyptian patients before and at least one year after treatment with DAAs using transient elastography and non-invasive liver fibrosis indices as FIB-4 and APRI scores. Patients and methods The present study was conducted on 100 patients with chronic hepatitis C patients attended to Ain Shams University Hospitals, Viral hepatitis treatment unit between October 2017 and December 2018, who were followed-up during treatment and after treatment for at least one year (retrospective and prospective study). Total number of cases during the study period was 117 patients. 17 patients were excluded from the study due to missed follow-up. Eventually, 100 patients were enrolled in the study fulfilling the inclusion criteria. Results The mean age of our patients is 47.9 years with Male predominance (52 males and 48 females). There was a significant improvement of, platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores. There was a significant improvement of liver stiffness after end of treatment, regardless of the DAA regimen used, as evidenced by Fibroscan. Conclusion Fibrosis regression –assessed by non-invasive markers of fibrosis is achievable upon removal of the causative agent.


2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.


2020 ◽  
pp. 488-494
Author(s):  
Mihaela Coșman ◽  
Ionuț Mihail Panțiru ◽  
Andrei Ionuț Cucu ◽  
Andreea Lenuța Atomei ◽  
Gabriela Florența Dumitrecu ◽  
...  

Introduction: The advantages and the necessity of intraoperative neurophysiological monitoring (IOM) in the surgery of motor area infiltrative tumours is well known. The use of this technique for Rolandic meningioma is still debatable. The absence or the loss of the cleavage plan and an infiltrative border make the dissection exceedingly difficult and increase the risk of new postoperative motor disfunction. Materials and methods: We evaluated the impact of IOM, especially direct cortical stimulation on the degree of resection, new postoperative deficits, symptom remission and clinical-imagistic aspects at one-year follow up of 19 cases of Rolandic meningioma admitted in Third Department of Neurosurgery,” Prof. Dr N. Oblu” Emergency Clinical Hospital, Yassi, Romania, between January 2014 and July 2018. Results: More than half of the cases (57,88%) had epileptic manifestations as the main clinical symptom with the Jacksonian seizures being on the first place (31,57%), followed by progressive paresis (26,31%) and other nonspecific symptoms. Intraparenchymal preoperative oedema was observed in 36,84% of patients. The intensity of direct cortical stimulation was between 6-13 mA (median = 9mA; mode = 12mA). Simpson degree of resection was dominated by S3– 47,36% and S4 was obtained in 15,78% of cases. Postoperative the outcome was favourable for 73,68% patients with 5,26% motor aggravation and 10,52% new deficits. At one-year follow up no imagistic recurrence was observed and the permanent motor deficit was maintained in one of the three cases (5,26%). Conclusion: Even though meningiomas are extranevraxial lesions and those located on the convexity have a low risk of complication, the absence of a clear dissection plan between the tumour and the adjacent motor cortex is associated with a high risk for new postoperative neurological deficits. Therefore, it is important to perform cortical mapping for Rolandic meningioma, to determine the location of the primary motor area and to protect it from mechanical and vascular trauma, during tumour resection.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Behnood Bikdeli ◽  
David Jimenez ◽  
Jorg Del Toro ◽  
Gregory Piazza ◽  
Augussina Rivas ◽  
...  

Background: Atrial fibrillation (AF) may occur prior to or early in the course of acute pulmonary embolism (PE). The impact of AF on outcomes of patients with PE remains uncertain. Methods: Using the data from a large prospective multicenter registry of patients with objectively-confirmed PE (04/2014 to 01/2020), we identified three patient groups: 1) those with pre-existing AF 2) patients with newly identified AF within 2 days from the index PE (incident AF) and 3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, in unadjusted and multivariable adjusted models considering those without AF as referent. Results: Among 16,497 patients with PE, 792 had pre-existing AF. Compared with those without AF, patients with pre-existing AF, had increased odds of 90-day all-cause (Odds ratio [OR]: 2.81 (95% confidence interval [CI]: 2.33-3.38) and PE-related mortality (OR: 2.38, 95% CI: 1.37-4.14). After multivariable adjustment, pre-existing AF significantly increased the odds of all-cause mortality (OR: 1.91, 95% CI: 1.57-2.32) but not PE-related mortality (OR: 1.50; 95% CI: 0.85-2.66). Pre-existing AF was associated with increased hazard for ischemic stroke at 1-year follow-up (hazard ratio [HR]: 5.48; 95% CI: 3.10-9.69). Among 16,497 patients with PE, 445 developed incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR: 2.28; 95% CI: 1.75-2.97) and PE-related (OR: 3.64; 95% CI: 2.01-6.59) mortality. Findings were similar in multivariable analyses and at 1-year follow-up (Figure). No patients with incident AF developed ischemic stroke. Conclusion: In patients with acute symptomatic PE, both pre-existing AF and incident AF predict an adverse clinical course, although the type of adverse outcomes may be different depending on the timing of AF onset.


RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001015 ◽  
Author(s):  
Fernando Pérez Ruiz ◽  
Pascal Richette ◽  
Austin G Stack ◽  
Ravichandra Karra Gurunath ◽  
Ma Jesus García de Yébenes ◽  
...  

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.


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