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.

scholarly journals Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 15 ◽  
pp. 175346662110280
Author(s):  
Roberto Ariel Abeldaño Zuñiga ◽  
Ruth Ana María González-Villoria ◽  
María Vanesa Elizondo ◽  
Anel Yaneli Nicolás Osorio ◽  
David Gómez Martínez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Clinical Improvement ◽  
Data Extraction ◽  
Meta Analysis ◽  
Clinical Effectiveness ◽  
Risk Of Bias ◽  
Hospitalized Patients ◽  
Low Risk ◽  
Controlled Clinical Trials

Aims: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. Methods: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. Results: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. Conclusion: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed. The reviews of this paper are available via the supplemental material section.

Trends in randomized controlled trials in ENT: a 30-year review

1997 ◽  
Vol 111 (7) ◽  
pp. 611-613 ◽  
Author(s):  
K. W. Ah-See ◽  
N. C. Molony ◽  
A. G. D. Maran
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Randomized Controlled Trials ◽  
Gold Standard ◽  
Controlled Trials ◽  
Evidence Based ◽  
Controlled Clinical Trials ◽  
Medline Search ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled

AbstractThere is a growth in the demand for clinical practice to be evidence based. Recent years have seen a rise in the number of randomized controlled clinical trials (RCTS). Such trials while acknowledged as the gold standard for evidence can be difficult to perform in surgical specialities. We have recently identified a low proportion of RCTS in the otolaryngology literature. Our aim was to identify any trend in the number of published RCTS within the ENT literature over a 30-year period and to identify which areas of our speciality lend themselves to this form of study design. A Medline search of 10 prominent journals published between 1966 and 1995 was performed. Two hundred and ninety-six RCTS were identified. Only five were published before 1980. Two hundred (71 per cent) of RCTS were in the areas of otology and rhinology. An encouraging trend is seen in RCTS within ENT literature.

Controlled Clinical Trials and Real-Life Experience with Pulmonary Rehabilitation

2017 ◽  
Vol 196 (6) ◽  
pp. 796-797
Author(s):  
Gayathri Sathiyamoorthy ◽  
Christopher Lau ◽  
Scott Marlow ◽  
Umur Hatipoğlu
Keyword(s):  
Clinical Trials ◽  
Pulmonary Rehabilitation ◽  
Life Experience ◽  
Real Life ◽  
Controlled Clinical Trials

Determination of the Percentage of CML Patients that Achieve Continuous Complete Molecular Response Under Treatment with TKIs and Are Eligible for Participation in a TKI Discontinuation Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4446-4446
Author(s):  
George Georgiou ◽  
Maria Roumelioti ◽  
Maria Dimou ◽  
Danai Palaiologou ◽  
Angeliki Stefanou ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Internal Control ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Tki Discontinuation ◽  
Complete Molecular Response

Abstract Abstract 4446 First-line therapy for Chronic Myeloid Leukemia (CML) is based on the tyrosine kinase inhibitor Imatinib, according to the published recommendations of the European Leukemia Net (Baccarani et al, JCO, 2009). CML patients that achieve the goals of treatment, remain under imatinib therapy for life, according to the ELN recommendations. Many CML patients treated for 5–10 years with imatinib ask about the possibility of stopping or reducing their treatment and poor imatinib adherence is observed in this group of CML patients. In the clinical trial STIM (STop IMatinib), Mahon FX et al., Lancet 2010,), 41% of 100 selected CML patients treated with imatinib that had achieved “complete molecular response” (CMR) for >2 years remained in CMR one year after discontinuation of Imatinib treatment. In patients with molecular relapse, re-introduction of imatinib resulted in molecular responses or CMR. This study demonstrated that a subpopulation of CML patients in CMR may discontinue safely imatinib. However the percentage of CML patients achieving CMR/ continuous CMR differs in published clinical trials and the definition of CMR is different between CML groups, since no standarization is currently available. Moreover, the actual percentage of CML patients that achieve CMR under TKI treatment in the every day clinical practice, outside of clinical trials (were several exlusion criteria exist), is not well defined. In the European trial Stop Kinase Inhibitors (EURO-SKI), it is planned to discontinue TKIs from CML patients that have received TKIs > 3 years and have CMR (according to EUTOS guidelines) for a minimum of 1 year. The aim of this study was to identify the percentage of CML patients treated with TKIs in the every day clinical practice, that meet the proposed EURO-SKI criteria.CMR was determined using the current definitions of EUTOS for CML for the determination of CMR: CMR4 (or molecular response MR4), when in a RQ-PCR, BCR-ABL1 transcripts are undetectable and the number of copies of the control abl gene are >10,000 and CMR 4,5 (or MR 4,5) when the number of the abl copies are > 32,000. In our Center, we monitor BCR-ABL1 levels in 510 CML patients treated with TKIs in 42 medical centers in Greece. Median age at diagnosis of CML is 58 years, 50.5% are females and median follow-up time 3.5 years. RQ-PCR is performed with the FusionQuant®Kit BCR-ABL (IPSOGEN,) where ABL1 is used as the internal control gene. Results: at the time of analysis 52 out of 510 CML patients (10.2%) were found to have CMR in at least 3 consecutive RQ-PCR assays during a period of at least 12 months and had received TKI therapy for at least 3 years; 41 out these 52 CML patients were in MR4 and 11 were in MR4.5. Conclusions: In an unselected population of CML patients, treated in routine clinical practice, 52 out of 510 (10.2%) achieved continuous CMR according to EUTOS guidelines and can be eligible to participate in TKI discontinuation studies. Disclosures: No relevant conflicts of interest to declare.

Real-Life Efficacy Of Azacitidine In Myelodysplastic Syndromes According To IPSS Cytogenetic Profile

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5229-5229
Author(s):  
Massimo Breccia ◽  
Maria Teresa Voso ◽  
Luca Maurillo ◽  
Pasquale Niscola ◽  
Luana Fianchi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Acute Leukemia ◽  
Stable Disease ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Risk Of Death ◽  
Cytogenetic Profile ◽  
Good Risk

Abstract In the AZA001 trial, azacitidine prolonged OS in all cytogenetic IPSS risk subgroups and in particular reduced 67% risk of death for all patients with -7/del(7q). Aim of our study was to assess azacitidine efficacy according to cytogenetic risk at baseline in a large group of intermediate/high-risk MDS patients treated outside clinical trials. One hundred and sixty-six patients represented the whole cohort of patients with primary or secondary MDS (CMML were excluded) diagnosed and treated with azacitidine in 6 different hematologic units. Patients were recruited consecutively, without any criteria of exclusion. All patients received azacitidine with a schedule of 5+2+2 or of 7 consecutive days every 28 days until progression or unacceptable toxicity. Clinical parameters (age, sex, WHO classification, IPSS) and baseline cytogenetic evaluation were retrospectively collected. Of 166 patients recruited, 103 were males and 63 females; median age was 69.5 years (range 49-89). A median of 8 cycles was performed (range 1-60). According to IPSS stratification there were 29 patients with intermediate-1 risk, 118 patients with intermediate-2 and 15 high–risk (7 patients not determined). According to WHO classification, 37 patients were diagnosed as having RAEB-1, 101 patients as RAEB-2, 28 patients as RCMD. According to IPSS cytogenetic risk stratification, 88 patients were in the good risk, 22 patients were in intermediate risk and 39 in the poor risk. The most frequent cytogenetic aberration, apart from normal karyotype, was -7 or del(7q). According to cytogenetic stratification, after a median of 4 cycles for the first evaluation, we revealed the following responses according to IWG criteria: of 88 patients classified as good risk, 68 were evaluable and overall 30% achieved a complete (CR), partial remission (PR) or hematological improvement (HI), 59% maintained a stable disease, 4% progressed to acute leukemia and 7% failed to achieve any response. Of 22 patients classified as intermediate cytogenetic risk, 19 patients were evaluable after 4 cycles: overall, 52.6% achieved a CR/PR and 42% maintained a stable disease, none experienced a progression and 5% failed to achieve any response. Of 39 patients stratified as high cytogenetic risk, 30 were evaluable: 36.6% achieved a CR/PR/HI, 36% maintained a stable disease, 20% progressed to acute leukemia and 7% failed to achieve any response. Our results, based on a retrospective evaluation in a large series of patients treated outside clinical trials, shown that azacitidine was clinically effective independently from cytogenetic profile, as proved in the AZA001 trial. Disclosures: No relevant conflicts of interest to declare.

Sustained Erythroid Response Associated With Red Cell Transfusion and Progressive Growth Factor Independence Is Feasible With Adjuvant Sertraline In Low-Risk Myelodysplastic Syndrome (LR-MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5235-5235
Author(s):  
Rui Li ◽  
Matthew Zheng ◽  
Sarvari Venkata Yellapragada ◽  
Ruben Hernandez Perez ◽  
Martha Mims ◽  
...  
Keyword(s):  
Growth Factor ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Conflicts Of Interest ◽  
Treatment Algorithm ◽  
Low Risk ◽  
Refractory Anemia ◽  
Cytokine Signaling ◽  
Absolute Increase ◽  
Erythroid Response ◽  
Tnf Α

Abstract Background LR-MDS is a heterogeneous group of clonal marrow disorder associated with ineffective hematopoeisis and complex genomic etiology. For patients (pt) with refractory cytopenia phenotype (RC-P), transfusion and growth factor support, such as Erythropoietin Stimulating Agents (ESAs) and Granulocyte Colony Stimulating Factor (G-CSF), are treatment options. Response rates for ESA is about 30%, (and response potentiation can be achieved in about 35% of pt receiving concurrent G-CSF.However, ESA unresponsiveness is a common phenomenon and is associated with transfusion dependence, normal/high EPO levels, and  high IPSS score. Therefore, novel therapies are greatly needed. Biologically, LR-MDS is linked to deregulation of apoptosis and cytokine signaling pathways. Selective Serotonin Reuptake Inhibitors (SSRIs) can induce normalization of deranged cytokines such as IL6 and TNF-α in clinical depression. In animal model of arthritis, sertraline abrogates manifestation of autoimmune arthritis by reducing TNF α. Our group recently showed that significant improvement in overall survival (OS) can be achieved in low-risk MDS patients treated with SSRIs, such as sertraline, which is independent of concurrent MDS directed therapy. (Li, et al. ASH 2012 abstract # 3818) Here, we report a case of sequential reversal of transfusion and growth factor dependence phenotype in a pt with refractory anemia multi-lineage dysplasia LR- MDS. Methods A 72-year male with transfusion dependent refractory anemia (8 units RBC in 8 weeks) was evaluated in clinic. His bone marrow showed erythroid and megakaryocytic dysplasia consistent with RCMD by WHO 2008 classification. Cytogenetic study revealed 45;X-Y[4];46 XY[16]. R-IPSS=1.5 (Cytogenetic=0; blast [0%] =0; Hb=7g/dL=1.5; Platelets [135000] =0; ANC [1500] =0). EPO and ferritin levels were 449 IU/L and 1600 NG/ML, respectively. R-H-EPO was administered at 40000 IU subcutaneously (SQ) per week. In view of severe depression, pt initiated sertraline at 100 mg orally on day (D) 61 of treatment. Response after 12 weeks of ESA, sequential addition of G-CSF and sertraline, were assessed according to internal working group (IWG) 2006 criteria. Results After 3 months of standard weekly SQ ESA (D1-D92) (Fig.1), and given ESA refractoriness, G-CSF at 480 mcg SQ 5-times weekly was added (ESA + G-CSF schedule) (D92-D189).Transfusion independence was observed by D 161 of combined ESA+G-CSF(Fig.1). Progressive hemoglobin stabilization resulted in G-CSF dose reduction to twice a week from D189 –D 257 (Fig. 1). Sequential resolution of ESA dependence was observed from D257- D515.  Over the treatment period, the absolute increase in Hb level was 4.2 g/dL from baseline. Restoration of ESA erythroid response was observed by D93-210 after G-CSF and sertraline addition. (Table. 1) Sustained and improved Hb levels were achieved after 200 days of G-CSF discontinuation and ESA dose de-escalation while on sertraline treatment. Conclusions Reversal of transfusion dependence represents a critical step in treatment algorithm of LR-MDS pt presenting with refractory anemia. In this context, ferritin normalization has previously been recognized as independent prognostic factor for outcome in MDS. Our case suggests feasibility of restoration of ESA sensitivity with concurrent G-CSF+ sertraline, and evidence for sustained beneficial effect of sertraline while ESA de-escalation, which seems independent from G-CSF. The MDS disease modifying effect of sertraline in LR- MDS patient presenting with refractory anemia and experiencing ESA refractoriness should be evaluated in prospective trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Approaches to Assessing the Quality of Observational Studies of Clinical Practice Based on the Big Data Analysis

2021 ◽  
Vol 17 (4) ◽  
pp. 584-593
Author(s):  
S. R. Gilyarevsky
Keyword(s):  
Clinical Trials ◽  
Big Data ◽  
Clinical Practice ◽  
Observational Studies ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Hierarchy Of Evidence

The article is devoted to the discussion of the problems of assessing the quality of observational studies in real clinical practice and determining their place in the hierarchy of evidence-based information. The concept of “big data” and the acceptability of using such a term to refer to large observational studies is being discussed. Data on the limitations of administrative and claims databases when performing observational studies to assess the effects of interventions are presented. The concept of confounding factors influencing the results of observational studies is discussed. Modern approaches to reducing the severity of bias in real-life clinical practice studies are presented. The criteria for assessing the quality of observational pharmacoepidemiological studies and the fundamental differences between such studies and randomized clinical trials are presented. The results of systematic reviews of real-life clinical trials to assess the effects of direct oral anticoagulants are discussed. 

Sign in / Sign up

Export Citation Format

Share Document