scholarly journals Epidemiology of Adults AML in Nord-Pas De Calais and Picardy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2281-2281
Author(s):  
Christophe Roumier ◽  
Céline Rodriguez ◽  
Cécile Frimat ◽  
Céline Berthon ◽  
Carole Delattre ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Molecular Biology ◽  
Median Survival ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Npm1 Mutation ◽  
Demethylating Agent ◽  
Molecular Abnormalities

Abstract Introduction AML is a heterogeneous group of neoplasm according to leukemogenic mechanisms and has variable response to treatment. In addition to age and WBC count at diagnosis, cytogenetic and molecular abnormalities are key factors to assess prognosis. In this work, we evaluated the number of adult AML cases diagnosed between 2009 and 2012 in the French Nord Pas de Calais and Picardie regions (North of France). The aim of the study was the collection of epidemiology data, treatments proposed and their results in real life. Matérials and Methods The Nord Pas de Calais and Picardie observatory contains data of all adult patients (>18 years) with AML (>20% marrow blasts) diagnosed in the oncology and/or hematology departments of the following participating Hospitals: Amiens (A), Arras (Ar), Boulogne (B), Dunkerque (D), Lens (L), Lille (CHRU et CH St Vincent (Vi)), Roubaix (R) et Valenciennes (V), whose overall catchment population is close to 6 million inhabitants , allowing a population based registry. A disadvantage of registry data is that investigators cannot control data collection and quality. In our observatory, data were obtained from the declaration of all the participants centralized with a web access reporting data base. The declaration of patients in the database was made both by clinicians, cytogeneticists and molecular biologists. The following data were entered:, disease course, WBC counts, bone marrow blast %, cytogenetics, immunophenotype, molecular biology, treatment received, outcome. To optimize data quality, each kind of data was entered respectively by clinicians, cytogeneticists and molecular biologists. Data were cross validated and the follow up data were updated every years during follow-up of the patients. Data was collected as of October 2013 Results Between January 2009 and December 2012, 899 patients were enrolled in the observatory, respectively 185 (A), 33 (Ar), 43 (B), 66 (D), 85 (L), 197 (CHRU), 57 (Vi), 98 (R) and 135 (V). Median age was 67 years (range 17 to 97), 54% of patients were older than 65 years, M/F was 1.12 (425 female (47%) et 474 male (53%)). Cytogenetic studies were performed in 87% of the patients, immunophenotype in 57%, molecular biology screening for FLT3 and NPM1 mutation in 61%. Intent of treatment was conventional chemotherapy (CTi) 50%, demethylating agent (DMT) 18% and best supportive care (BSC) 32% + Low dose cytarabine (LDAC). The overall median survival was 269 days (624d < 65 y and 115d for > 65 y) (fig1). 15% of the patients (132pts) were included in a clinical trial (90 % <65 y and 10% >65 y). Median overall survival of the patients included in a clinical trial and aged <65y was 1121d vs 563d for patients not included in a clinical trial and aged <65y (p:ns). Of the 482 patients aged >65 y, MRC cytogenetic classification was unfavourable (139 pts; 29%), intermediate (209 pts; 43%), favourable (18 pts; 4%) and not done 116 pts (24%). Overall, in pts aged > 65, treatment was CTI 93 pts (19%), DMT 130 pts (27%), BSC 210 pts (44%), LDAC) 38 pts (8%), others 11 pts (2%). Among pts with unfavourable karyotype treatment was: Cti (14%), DMT (45%), LDAC (2%), BSC (38%) and others (1%). overall median survival in this unfavourable group was 222d with DMT vs 104d with LDAC vs 227d with CTI. In intermediate cytogenetics cases, treatment was Cti (24%), DMT (19%), LDAC (14%), BSC (42%) and other (1%), and median OS was 270d with DMT vs 189d with ARAC-LD vs 378d with Cti. Demethylating agent treatment results were different between MRC groups. In the intermediate MRC group of pts >65y, OS was better with CTI vs DMT (p:0.03), whereas in the unfavorable pts group aged >65y/o, DMT treatment seemed to be as effective than Cti (fig 2 and 3). Conclusion This registry study gives a real life idea of the therapeutic intent in AML patients, stressing in particular the small proportion of patients who can be included in clinical trials due to comorbidity and also the small number of available clinical trials in elderly patients, due to the current lack of promising drug apart from IC (among pts>65y/o only 13 pts have been included). Our observatory shows that in pts >65 y/o the intent of treatment should take account MRC classification, CTI being more effective that DMT or LDAC only in intermediate cases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment Burden in Patients with Multiple Myeloma According to Comorbidity

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4775-4775
Author(s):  
Ernesto Pérez Persona ◽  
Ariane Unamunzaga Cilaurren ◽  
Ana Vega Gonzalez de Viñaspre ◽  
Itziar Oiartzabal Ormategui ◽  
Ana Santamaría Lopez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Progression Free Survival ◽  
P Value ◽  
Treatment Burden ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Time To Death

Abstract Introduction: Over the last few years, novel agents-based combinations have been incorporated into the treatment of MM patients, particularly in relapse setting. However, these novel combinations have been evaluated in clinical trials and patients included represent a selected population. Patients in real life are usually older with comorbidities and disabilities and not allowed to be included in the trials, so, in real setting, is expected worse outcomes and shorter survival. The information about treatment burden in real life is scarce. The aim of our study was to analyze the outcome of MM patients in the real life outside clinical trials, in terms of treatment lines in a single institution setting, and to analyze the influence of comorbidities on the treatment burden. Material and methods: Medical records of MM patients treated at Txagorritxu hospital (Spain) between 2009 and January 2017 were retrospectively evaluated with the aim of mapping the course of patients as well as to investigate the factors that influence treatment-decisions at different stages of the disease. Results: 176 patients with MM were diagnosed from jan-2009 to jan-2017. Baseline patient's characteristics are presented in Table 1. The median age at diagnosis was 71 years (range 33.2-93), main of the patients where non-transplant eligible newly diagnosed MM (NTENDMM): 114 (65%). With a median follow-up of 25 months, 90.6% of newly diagnosed MM patients transplant-eligible (TENDMM) remain alive versus 65% NTENDMM patients (p value: 0.000)(figure 1). Overall, patients received a median of 2 lines of treatment, it should be noted that 86% of patients had received 3 or less lines of treatment and only 14% of the patients could receive more than 3 lines of therapy. To better evaluate treatment burden, we focused on deceased patients. At the time of analysis, 19% of TENDMM (12 patients) and 51.4% of in NTENDMM (57 patients) has died with a median time to death of 29.6 months and 18 months to death, respectively. Median lines of therapy for death patients TENDMM was 3.5 (range 1-8), with a 75 percentile of 5 lines of therapy, by contrast, death NTENDMM patients received a median of 2 lines of therapy (range: 1-6), with an 80 percentile of 3 lines of therapy (figure 2). In order to evaluate the influence of comorbidities in treatment burden for NTENDMM patients, CIRS score was estimated retrospectively. Median CIRS score was 5.5 (1-19). CIRS scale did not predict progression free survival (PFS) among the different groups: CIRS <4: 23.4 months; CIRS4-8: 25.1 months and CIRS> 8: 30.6 months (p: 0.819), however, interestingly CIRS scale predicted overall survival (OS): CIRS <4: 48 moths; CIRS4-8: 50.8 months and CIRS> 8: 12.3 months, (p: 0.012) (figure 2). Analyzing treatment burden for each CIRS score group 63% of patients with CIRS> 8 received only one line of treatment before death, compared to 39.5% and 37.5% of patients with CIRS4-8 and CIRS <4, respectively. Conclusion: Although the impressive progress in the management of relapse/refractory MM patients in recent years, half of the patients, particularly those not suitable to received an autologous transplant, will be able to received only 2 lines of treatment before dying. In fact, an adequate comorbidity assessment could select patients that will only need only one line of treatment. To the best of our known, this is the first study that correlate treatment burden according to comorbidities at diagnostic. This study could guide strategies adapted according to the comorbidity of the patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals SO093LONGITUDINAL DATA ON TREATMENT DURATION AND COMPLIANCE FROM AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS WITH TOLVAPTAN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xiaolei Zhou ◽  
Diana Garbinsky ◽  
John Ouyang ◽  
Eric Davenport ◽  
Indra Agarwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Treatment Duration ◽  
Treatment Time ◽  
Treatment Compliance ◽  
Kidney Volume ◽  
Total Kidney Volume ◽  
Treatment Gaps ◽  
Clinical Trial Program

Abstract Background and Aims : Observation of impactful clinical outcomes in a clinical trial setting for ADPKD is challenging due to the life-long progressive nature of ADPKD and longer-term associated outcomes of interest in this population (e.g., renal function decline, cardiovascular events, and mortality). Since 2004, the tolvaptan (TOL) clinical trial program enrolled subjects in multiple clinical studies with the opportunity to enroll in subsequent clinical trials for treatment and outcomes evaluation. Method : Data from 6 ADPKD studies (protocols 156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271) were pooled and evaluated over time for overall treatment duration, treatment time, and treatment gaps. Treatment duration for the individual clinical trials ranged from 1 week to up to 3 years. Results : Overall, 1,437 subjects received TOL in these ADPKD clinical trials. For these subjects, the mean overall treatment duration was 4.1 years (3.8 years on treatment) with a maximum of 9.7 years (9.0 years on treatment). In this cohort, 513 subjects (35.7%) received TOL treatment for more than 5 years. Mean treatment compliance was 94.1%. Overall, 723 subjects (50.3%) received TOL treatment in ≥2 trials, with a median treatment gap duration between trials of 0.1 years (maximum, 5.6 years). At least 7 years of follow-up data are available for estimated glomerular filtration rate in 241 subjects (mean at baseline, 78.6 mL/min/1.73m2) and for total kidney volume in 130 subjects (mean at baseline, 1,816.9 mL). Conclusion : This analysis provides longitudinal follow-up over an extended timeframe in a large number of subjects treated with TOL, with the greatest number of subjects being enrolled in clinical trials enriched for rapidly progressing ADPKD. Treatment compliance over years was reasonably good despite treatment gaps.

Dedicated clinical trial tissue tracking database to improve turn-around time at high-volume center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1543-1543
Author(s):  
Peter Blankenship ◽  
David DeLaRosa ◽  
Marc Burris ◽  
Steven Cusson ◽  
Kayla Hendricks ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tissue Sample ◽  
High Volume ◽  
Trial Participation ◽  
Fresh Tissue ◽  
Oncology Clinical Trials ◽  
The Status ◽  
Unique Source

1543 Background: Tissue requirements in oncology clinical trials are increasingly complex due to prescreening protocols for patient selection and serial biopsies to understand molecular-level treatment effects. Novel solutions for tissue processing are necessary for timely tissue procurement. Based on these needs, we developed a Tissue Tracker (TT), a comprehensive database for study-related tissue tasks at our high-volume clinical trial center. Methods: In this Microsoft Access database, patients are assigned an ID within the TT that is associated with their name, medical record number, and study that follows their request to external users: pathology departments, clinical trial coordinators and data team members. To complete tasks in the TT, relevant information is required to update the status. Due to the high number of archival tissue requests from unique pathology labs, the TT has a “Follow-Up Dashboard” that organizes information needed to conduct follow-up on all archival samples with the status “Requested”. This results in an autogenerated email and pdf report sent to necessary teams. The TT also includes a kit inventory system and a real-time read only version formatted for interdepartmental communication, metric reporting, and other data-driven efforts. The primary outcome in this study was to evaluate our average turnaround time (ATAT: average time from request to shipment) for archival and fresh tissue samples before and after TT development. Results: Before implementing the TT, between March 2016 and March 2018, we processed 2676 archival requests from 235 unique source labs resulting in 2040 shipments with an ATAT of 19.29 days. We also processed 1099 fresh biopsies resulting in 944 shipments with an ATAT of 7.72 days. After TT implementation, between April 2018 and April 2020, we processed 2664 archival requests from 204 unique source labs resulting in 2506 shipments (+28.0%) with an ATAT of 14.78 days (-23.4%). During that same period, we processed 1795 fresh biopsies (+63.3%) resulting in 2006 shipments (+112.5%) with an ATAT of 6.85 days (-11.3%). Conclusions: Oncology clinical trials continue to evolve toward more extensive tissue requirements for prescreening and scientific exploration of on-treatment molecular profiling. Timely results are required to optimize patient trial participation. During the intervention period, our tissue sample volume and shipments increased, but the development and implementation of an automated tracking system allowed improvement in ATAT of both archival and fresh tissue. This automation not only improves end-user expectations and experiences for patients and trial sponsors but this allows our team to adapt to the increasing interest in tissue exploration.

MO368THE INCIDENCE AND RISK FACTORS FOR ACUTE KIDNEY INJURY IN PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A REAL-LIFE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Deniz Can Güven ◽  
Deniz Aral Ozbek ◽  
Taha Koray Sahin ◽  
Melek Seren Aksun ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Kidney Disease ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Real Life ◽  
Kidney Injury

Abstract Background and Aims The immune checkpoint inhibitors (ICIs) became a vital part of cancer treatment. The ICIs seem to be safer than chemotherapy for kidneys in clinical trials. However, recent observational studies from high-resource settings pointed out the possible underreporting of renal adverse events like acute kidney injury (AKI) in the clinical trials due to focusing only to the renal immune-related adverse events. Additionally, clinical trials generally enroll a fitter population with lesser comorbidities and include mostly treatment-naive patients making studies in real-life cohorts imperative for evaluating the AKI rates during ICI treatment. From these points, we aimed to evaluate the AKI rates and predisposing factors in ICI-treated patients. Method This retrospective study has evaluated the data of adult metastatic cancer patients treated with ICIs in Hacettepe University Cancer Center from 01.2014 to 12.2019. All patients other than the ones treated within the context of clinical trials or followed in other institutions after the first dose of ICIs were included. Baseline demographics, cancer types, patient weight and heights, ICI type and the number of cycles, serum creatinine and the estimated GFR values under treatment, regular medications, and comorbidities were recorded. AKI was defined by Kidney Disease Improving Global Outcomes criteria. The predisposing factors to AKI development were evaluated with the univariate and multivariate analyses. Results A total of 147 patients were included in the analyses. Median age was 61 [interquartile range (IQR) 51-67], and 69.4% of the patients were male. Patients were given a median of 8 (IQR 5-17) ICI cycles. Patients with melanoma (24.5%), non-small cell lung cancer (15%), and renal cell carcinoma (25.9%) comprised almost 2/3 of the cohort and 72.8% of the patients were treated with nivolumab. Hypertension was the most common comorbidity (38.1%), followed by chronic kidney disease (21.2%) and type 2 diabetes (19.7%). Median Charlson Comorbidity Index (CCI) was 8 (7-9). Median follow-up was 10.3 (IQR 6.3-19.4) months, and patients had median 9 (IQR 5-18) serum creatinine measurements. During the follow-up, 28 patients (19%) had at least one AKI episode with multiple AKI episodes in 3 patients (10.7%). The median time to AKI development was 2.53 (IQR 1.39-6.19) months. Almost all AKI events were mild (grade 1 or 2 in 27/28) and reversible (25/28). In univariate analyses, coronary artery disease (CAD) (p=&lt;0.001), chronic kidney disease (CKD) (p=0.002), previous nephrectomy (p=0.015), iodinated contrast exposure in the week before immunotherapy (p=0.035), the use of renin-angiotensin-aldosterone system inhibitors (p=0.046) or proton pump inhibitors (PPI) (p=0.041) was associated with an increased AKI risk. The association between diabetes (p=0.067), higher CCI (9 vs. ≥9, p=0.107), baseline lactate dehydrogenase levels (p=0.177), and performance status (ECOG 0 vs. ≥1, p=0.235) and AKI risk did not reach statistical significance. In multivariate analyses, patients with CKD (OR: 3.719, 95% CI: 1.375- 10.057, p=0.010) or CAD (OR: 4.774, 95% CI: 1.803- 12.641, p=0.002) had increased AKI risk. Additionally, regular PPI use (OR: 2.734, 95% CI: .991- 7.542, p=0.052) had borderline statistical significance for AKI development. The development of AKI was not associated with decreased survival (HR: 0.726, 95% CI: 0.409-1.291, p=0.276). Conclusion In this study, we observed AKI development under ICIs in almost one in five cancer patients. The increased AKI rates in patients with CAD, CKD, or regular PPI use pointed out the need for better onco-nephrology collaboration in all ICI-treated patients, with a particular emphasis in these high-risk patients.

scholarly journals Results availability and timeliness of registered COVID-19 clinical trials: interim cross-sectional results from the DIRECCT study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e053096
Author(s):  
Maia Salholz-Hillel ◽  
Peter Grabitz ◽  
Molly Pugh-Jones ◽  
Daniel Strech ◽  
Nicholas J DeVito
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Journal Article ◽  
Cross Sectional Study ◽  
Sensitivity Analyses ◽  
Cross Sectional ◽  
Registration Data ◽  
Clinical Trial Registries ◽  
Treatment And Prevention

ObjectiveTo examine how and when the results of COVID-19 clinical trials are disseminated.DesignCross-sectional study.SettingThe COVID-19 clinical trial landscape.Participants285 registered interventional clinical trials for the treatment and prevention of COVID-19 completed by 30 June 2020.Main outcome measuresOverall reporting and reporting by dissemination route (ie, by journal article, preprint or results on a registry); time to reporting by dissemination route.ResultsFollowing automated and manual searches of the COVID-19 literature, we located 41 trials (14%) with results spread across 47 individual results publications published by 15 August 2020. The most common dissemination route was preprints (n=25) followed by journal articles (n=18), and results on a registry (n=2). Of these, four trials were available as both a preprint and journal publication. The cumulative incidence of any reporting surpassed 20% at 119 days from completion. Sensitivity analyses using alternate dates and definitions of results did not appreciably change the reporting percentage. Expanding minimum follow-up time to 3 months increased the overall reporting percentage to 19%.ConclusionCOVID-19 trials completed during the first 6 months of the pandemic did not consistently yield rapid results in the literature or on clinical trial registries. Our findings suggest that the COVID-19 response may be seeing quicker results disclosure compared with non-emergency conditions. Issues with the reliability and timeliness of trial registration data may impact our estimates. Ensuring registry data are accurate should be a priority for the research community during a pandemic. Data collection is underway for the next phase of the DIssemination of REgistered COVID-19 Clinical Trials study expanding both our trial population and follow-up time.

scholarly journals Patients with cancer in the COVID-19 era: the clinical trial issue

2020 ◽  
Vol 106 (4) ◽  
pp. 271-272 ◽  
Author(s):  
Marcello Scarcia ◽  
Giuseppe Mario Ludovico ◽  
Angela Fortunato ◽  
Alba Fiorentino
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Physical Examination ◽  
Regulatory Agencies ◽  
Study Medication ◽  
Therapeutic Modalities ◽  
Patients With Cancer ◽  
Safety Guidelines ◽  
Trial Discontinuation

Coronavirus disease 2019 (COVID-19) hospital reorganization may result in reduced ability for the hospital to fully use its armamentarium for battling cancer. Thus different therapeutic modalities have been recommended. During the pandemic, despite regulatory agencies’ recommendations, several considerations and doubts remain for oncologic clinical trials. Considering patients who had been enrolled before the pandemic, and who plan to take the study medication, the situation becomes complicated. These patients should undergo monitoring visits, blood sampling, questionnaire, physical examination, and drug and radiation administration. To avoid deviations from the protocol and trial discontinuation, follow-up should be performed regularly, in concordance with safety guidelines. Here we report several considerations.

scholarly journals Parental perspectives long term after neonatal clinical trial participation: a survey

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Thomas Salaets ◽  
Emilie Lavrysen ◽  
Anne Smits ◽  
Sophie Vanhaesebrouck ◽  
Maissa Rayyan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Trial Participation ◽  
Drug Trials ◽  
Clinical Trial Participation ◽  
Parental Perspectives ◽  
Positive Experiences ◽  
Almost All

Abstract Background Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial. Methods Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3–13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales. Results Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware). Conclusions Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.

Monitoring of Minimal Residual Disease in NPM1 Mutated Acute Myeloid Leukemia (AML) – a Single Center Experience in 27 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4672-4672
Author(s):  
Dana Dvorakova ◽  
Zdenek Racil ◽  
Ivo Palasek ◽  
Marketa Protivankova ◽  
Ivana Jeziskova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Npm1 Mutation ◽  
Mgb Probe ◽  
Minimal Residual

Abstract Abstract 4672 Background Mutations within NPM1 gene occurs in about 60% of adult cytogenetic normal AML (CN-AML) and represent the single most frequent molecular aberration in this subgroups of patients. These mutations usually occur at exon 12 and induce most frequently a net insertion of four base pairs. Aims To examine the applicability and sensitivity of DNA-based real-time quantitative polymerase chain reaction (RQ-PCR) with mutation-specific reverse primers and common minor groove binding (MGB) probe and to evaluate whether minimal residual disease levels are of prognostic relevance in CN-AML patients with NPM1 mutations. Methods Patients were treated within different AML trials and follow-up samples of peripheral blood or bone marrow were referred to perform an RQ-PCR. Samples were analysed at diagnosis, during, and after therapy. The NPM1 mutations were A (17 pts), B (1 pt), D (2 pts) and 7 patients with individual rare types. For all cases, levels of minimal residual disease were determined by DNA-based RQ-PCR with mutation-specific reverse primer, one common forward primer and one common MGB probe. The NPM1 mutation value was normalized on the number of albumin gene copies and expressed as the number of NPM1 mutations every 106 genomic equivalents. This assay is highly specific as no wildtype NPM1 could be detected. Maximal reproducible sensitivity was 10 plasmide molecules per reaction. Results A total of 950 samples of bone marrow and/or peripheral blood from 27 patients have been analyzed. Twenty of 27 patients (74%) achieved molecular remission (MR), twenty-six of 27 patients (96%) achieved hematological remission (HR). 6 of 27 (22%) patients achieved HR without MR and one patient failed therapy. 8 of 20 patients (40%) with MR after treatment relapsed at molecular level and except one in all these patients hematological relaps occured (one patient is still in HR with bone marrow blast present, but < 5%). Considering relapsed patients, time from molecular to hematological relapse was 1 to 5 months (median: 3 months). Considering all 14 patients with HR without MR (6 pts) or with molecular relapse (8 pts), in 11 of them hematological relaps occured (79%) and molecular positivity anticipating hematological relaps with median of 3,5 month (1-7 months). 3 of these 14 patients are still in HR. Conclusions Mutations within NPM1 gene are a sensitive marker for monitoring minimal residual disease in CN-AML patients. RQ-PCR using a MGB probe is an efficient approach to long-term follow-up of residual leukemia cells and frequent quantitative monitoring is useful for reliably predicting hematological relapse. Achievement of negativity appears to predict favorable clinical outcome. This work was partially supported by research grant No. MSM0021622430 Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Clinical and Tumor Associated Variables in a Population-Based Cohort of Mantle Cell Lymphomas in the Stockholm Region Between 1998–2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1592-1592 ◽  
Author(s):  
Stefanie Baumgartner Wennerholm ◽  
Monika Klimkowska ◽  
Lina Nygren ◽  
Eva Kimby ◽  
Birgitta Sander
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Median Survival ◽  
Biological Markers ◽  
Population Based ◽  
Prognostic Impact ◽  
Female Ratio ◽  
Significant Difference ◽  
Mantle Cell

Abstract Abstract 1592 Introduction: Mantle cell lymphoma (MCL) constitutes 3–10% of non-Hodgkin lymphomas and affects predominantly middle-aged to elderly men. The median survival is 3–5 years and seems to improve with new therapeutic regimens. The MCL International Prognostic Index (MIPI) has been proven useful for predicting survival in MCL patients included in clinical trials, but its value in unselected population based MCL cohorts is less well known. Biological markers are increasingly used for prognostication of MCL patients, especially for defining indolent cases. Material and Methods: All 186 patients diagnosed with MCL, confirmed by IHC for cyclinD1 and/or by FISH for t(11;14), between January 1998 and June 2010 in the Stockholm region, were included in a retrospective analysis. Clinical data from patient files, diagnostic biopsies and flow cytometry data were reviewed. Last follow-up was in May 2011. The prognostic value of the following variables, evaluated at the time of diagnosis, were analyzed: age, sex, Ann Arbor stage, ECOG, B-symptoms, Hb, LDH, albumin, lymphocytosis, leukocytosis, splenomegaly, nodal, extranodal and bone marrow involvement, blastoid morphology, expression of CD23, light chain, Ki 67, p53 and nuclear SOX11. Results: The median age at diagnosis was 68.8 years (range 36.2 – 89.9); 67.4 in males and 72.1 in females, respectively. The male: female ratio was 2. Thirty patients had a known malignancy of other type before the MCL diagnosis and 12 acquired a cancer later. In 13 patients the other malignancy was the cause of death. Median overall survival (OS) time was 43 months in the whole cohort and 38 months, when excluding 39 patients receiving ASCT as part of first-line therapy. No statistically significant difference in OS was seen with respect to whether the lymphoma was diagnosed before or after 2005. In the non-transplanted patients (n=149), univariate analysis showed the following clinical variables to be negatively correlated to overall survival: age >65 years, B-symptoms, splenomegaly, ECOG >2, low albumin, and high LDH. The median survival was not reached in the low risk MIPI group, and was 79 and 34 months, in the middle and high risk MIPI group, respectively. Blastoid morphology and p53 positivity (>20%), were negatively correlated to overall survival (both with p<0.0001), as was increasing tumor cell proliferation (measured as a continous variable or using the cut-offs >50%, both with with p<0.0001), but not with cut-off >30% (p=0.061), while SOX11 positivity was related to a prolonged survival (p=0.015). Multivariate analyses showed that age >65 (HR 6.1, p<0,002), ECOG >2 (HR 63, p<0.001), high LD (HR 3.7, p< 0.001), and p53 positivity (HR 5.6, p< 0.0001) remained significant. Clinically indolent MCL, defined as in retrospect not requiring treatment within two years from diagnosis, was seen in 17 patients. In two of these patients the proliferation was >30%, in one >50%, two had a p53 expression >20% and two were SOX11 negative. Therapy was never required in 9 of these initially indolent patients and only one had an autologous transplantion later in the disease course. The median OS was 72 months for the 17 indolent MCL compared with 34 months in patients requiring treatment earlier in their disease (p=0.003). The follow-up time did not differ significantly between the two groups. Conclusions: Compared to data from published clinical trials of advanced MCL, our population-based cohort of 186 cyclin D1 positive MCL patients were diagnosed at an older age, which may contribute to a shorter overall survival. Certain well-established prognostic variables seem to loose significance outside study populations. In the group of 147 non-transplanted patients multivariate analysis showed that only age, ECOG, LDH and p53 positivity were independently associated with overall survival. Leukocytosis as a variable of MIPI had no impact. Neither SOX11, CD23 or other biological markers applied at the time of diagnosis could predict for clinically indolent disease. Disclosures: No relevant conflicts of interest to declare.

Response to Erythropoietin in a Multicentric Real-Life Cohort of Myelodysplastic Patients: The Grom Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4958-4958
Author(s):  
Roberto Latagliata ◽  
Maria Antonietta Aloe Spiriti ◽  
Luca Maurillo ◽  
Carolina Nobile ◽  
Anna Lina Piccioni ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Transfusion Requirement ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Low Risk ◽  
Controlled Clinical Trials ◽  
University Hospitals ◽  
Erythroid Response ◽  
High Doses

Abstract Abstract 4958 Erythropoietin (EPO) have been widely employed in the treatment of patients with low-risk Myelodysplastic Syndromes (MDS) and anemia, with response rates ranging from 30 to 60%. These data, however, have been derived only from controlled clinical trials or unicentric single-arm studies; it is still lacking a wider survey evaluating the use of EPO in the real-life clinical practice. To address this issue, the Gruppo Romano Mielodisplasie (GROM) revised retrospectively 394 MDS patients (M/F 225/169, median age at diagnosis 73. 9 yrs, IR 67. 0 – 79. 3) treated with EPO from 1/2002 to 12/2010 by 11 Hematological Centers (5 university hospitals and 6 community-based hospitals) in the metropolitan area of Rome. According to WHO classification, there were 81 (20. 6%) patients with RA, 7 (1. 8 %) with SA, 160 (40. 7%) with RCMD, 17 (4. 3%) with RCMD-S, 75(19. 0%) with RAEB-1, 27 (6. 8%) with RAEB-2 and 27 (6. 8%) with isolated del5q. The IPSS score was calculated in the 307 patients with an available karyotype: 145 (47. 2%) patients were low-risk, 135 (44. 0%) int-1, 24 (7. 8%) int-2 and 3 (1. 0%) high-risk. Median interval from diagnosis to EPO start was 3. 7 months (IR 0. 9 – 12. 1). At EPO start, median age was 74. 5 yrs (IR 68. 3 – 79. 9) with a median haemoglobin level of 8. 9 g/dl (IR 8. 2 – 9. 6). Creatinine level was elevated in 64 (16. 2%) cases: 138 patients (35. 3%) had a previous transfusion requirement. Median serum EPO level was 50. 0 mU/L (IR 26. 2 – 110. 0). The initial doses of EPO were ≤ 40. 000 UI/week in 259 patients (65. 7%) (standard doses, α-EPO in 104 patients, β-EPO in 143 patients, darbepoietin in 12 patients) and 80000 UI/week in 135 patients (34. 3%) (high doses, α-EPO in 130 patients, β-EPO in 5 patients). An erythroid response was observed in 228 (57. 9%) patients, with Hb increase > 1. 5 g/dl in 210 patients (53. 3%) and disappearance of transfusion requirement in 18 (4. 6%): patients receiving initial high doses had a higher response rate compared to patients receiving standard doses [94/135 (69. 6%) vs 134/259 (51. 7%), p=0. 002]. Only 5 thrombotic events (1. 2%) were reported during the treatment. Predicting factors for erythroid response were no previous transfusion requirement (p<0. 001), serum EPO levels at baseline < 50 mU/l (p<0. 001), creatinine levels above the normal values (<0. 001), ferritin levels < 250 ng/ml (p=0. 009) and hemoglobin level at baseline > 8 g/dl (p=0. 017). Median overall survival from EPO start was 70. 7 months (CI 95% 52. 5 – 88. 8) in responders versus 41. 7 months (CI 95% 27, 6 – 55, 7) in resistant patients (p= 0. 018). Our real-life data from a single homogeneous geographic area outline that EPO treatment is safe and effective also in the current clinical practice, beyond controlled clinical trials. However, this latter type of studies is warranted to define the best initial dose of EPO in such patients. Disclosures: No relevant conflicts of interest to declare.

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