scholarly journals Erythropoiesis Stimulating Agents (ESAS) in Supportive Care of Low-Risk Myelodysplastic Syndromes: Recamds Registry FINAL Results

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5038-5038
Author(s):  
Claudio Cerchione ◽  
Fiorella Alfinito ◽  
Orsola Vitagliano ◽  
Ilaria Soriente ◽  
Paolo Danise ◽  
...  
Keyword(s):  
Standard Dose ◽  
Low Risk ◽  
Continuous Treatment ◽  
Erythropoiesis Stimulating Agents ◽  
Frontline Treatment ◽  
Progression Of Disease ◽  
Hb Concentration ◽  
Mean Time ◽  
Erythropoietic Response ◽  
Stimulation Of

Abstract Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. 183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118). ORR was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic. These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses. Figure 1 Figure 1. Disclosures Martinelli: Roche: Consultancy; Stemline Therapeutics: Consultancy; Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau.

EFFECTS OF INCREASING DOSES OF PYROGLUTAMYL-HISTIDYL-PROLINE AMIDE ON SERUM THYROTROPHIN LEVELS IN NORMAL SUBJECTS

1972 ◽  
Vol 70 (1) ◽  
pp. 196-208 ◽  
Author(s):  
Bengt Karlberg ◽  
Sven Almqvist
Keyword(s):  
Normal Saline ◽  
Standard Dose ◽  
Normal Subjects ◽  
Response Curves ◽  
Clinical Observations ◽  
Trh Stimulation ◽  
Stimulation Tests ◽  
Serial Measurements ◽  
Serum Tsh ◽  
Stimulation Of

ABSTRACT The effects of the administration of normal saline in four normal subjects and the single iv injections of synthetic pyroglutamyl-histidyl-proline amide (TRH) in doses of 6.25, 12.5, 25, 50, 100, 200 and 400 μg in 12 healthy subjects were evaluated by clinical observations and serial measurements from −10 to + 360 minutes of serum TSH, PBI, STH, cholesterol, glucose and insulin. Normal saline and TRH 6.25 μg iv did not change the serum TSH level. The minimum iv dose of TRH increasing serum TSH within 10 minutes was 12.5 μg. Nine of 12 subjects gave maximal increases of serum TSH after TRH 100 μg and all after 200 and 400 μg. The time for the peak response varied with the dose from 15 to 60 minutes. The dose-response curves, average and individual, were complex and not linear. This was interpreted as a varying degree of stimulation of both pituitary synthesis and release of TSH by TRH. PBI changes were measured at 2 h and 6 h. Minimum dose for a significant increase of PBI was 12.5 μg and 6.25 μg of TRH for the respective times. No change in basal STH-levels occurred in 53 of 65 TRH-stimulation tests. Nine of the 12 changes in serum STH occurred in four subjects with varying basal STH-levels. No changes were found in serum cholesterol, glucose or insulin. Our results show that 50 μg of TRH can be used as a standard dose for the single iv stimulation of pituitary release of TSH. TRH stimulated both TSH and STH release in 18% of our tests.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

Điều trị tăng liều Imatinib trên bệnh nhân u mô đệm đường tiêu hoá giai đoạn muộn tiến triển sau điều trị bước 1 liều chuẩn

2020 ◽  
Author(s):  
Kien Do Hung
Keyword(s):  
Primary Tumor ◽  
Standard Dose ◽  
Performance Status ◽  
Gastric Tumor ◽  
High Dose ◽  
Time To Failure ◽  
Gastrointestinal Stromal Tumours ◽  
Mean Time To Failure ◽  
The Mean ◽  
Mean Time

Objective: Evaluating the result of high-dose imatinib for metastatic gastrointestinal stromal tumours after failure standard-dose first line. Patients and method: Restrospective analysis of 46 patients with metastatic gastrointestinal stromal tumours after failure standard-dose imatinib treated with high-dose imatinib at K hospital from 1/2015 đến 10/2019. Results: Median age was 54.6±9.5, male was 58.7%. The common primary tumor was gastric tumor. The mean time to failure of imatinib standard-dose 400mg/day was 38.2±5.3 months. Liver lesions were the most common lesions progressed after imatinib standard-dose failure (71.7%), primary tumor progressed was 39.1%. There was no patient who had complete response with treatment, the proportion of partial response accounted for 21.7% and stable disease was 45.7%. The clinical benefit rate was 67.4%. The sex-female, primary gastric tumor, good ECOG performance status, neutrophils, hemoglobine and albumin before treatment were the significant prognostic factors affecting the treatment response, p <0.05. The mean time to failure was 22.5 ± 3.4 (months), (min: 2.0; max: 58.0), median was 11.0 months. Conclusion: Treatment of high-dose imatinib after failure standard-dose 400mg/day showed the efficacy and good tolerance in metastatic GISTs.

THROMBOLYSIS BY TISSUE-PLASMNOCEN ACTIVATOR AND A FIBRIN (OCEN) -DEGRADATION PRODUCT, PEPTIDE 6A, IN A CANINE MDDEL OF ELECTRICALLY-INDUCED CORONARY THROMBOSIS

1987 ◽  
Author(s):  
T Saldeen ◽  
J Mehta ◽  
W Nichols ◽  
D Lew
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Thrombosis ◽  
Canine Model ◽  
Peak Effect ◽  
Endothelial Surface ◽  
Tissue Plasminogen ◽  
Flow Restoration ◽  
Mean Time ◽  
Stimulation Of

Intracoronary thrombus resulting in acute myocardial ischemia can be lysed by thrombolytic agents, such as, streptokinase or t-PA. We examined the potential of a recombitant tissue-plasminogen activator (rt-PA)and a fibrin (ogen)-degradation productpentapeptide 6A, Ala-Arg-Pro-Ala-Lys, corresponding to aminoacids 43-47 in the BB-chain of fibrinogen, which causes marked increase in coronary blood flow and stimulates prostacyclin release, in restoring coronary blood flow in dqgs with experimentally-induced thrombus. An occlusive thrombus was created in the circumflex (Cx) coronary artery in 8 dcgs by electricalstimulation of the endothelial surface. The electrically-induced Cx thrombus consisted primarily of platelets and fibrin. After the occlusive thrcmbus was stable without electrical currant, rt-PA (10ug/kg/minute for 30 minutes intravenously)or peptide 6A (5 unoles/minute for 20 minutes intracorcnary) were randomly administered. Infusion of t-PA restored coronar blood flow (peak 22 ±12 ml/minute, mean ±SD) in five of seven animlas. The time to flow restoration was 12.3 ± 9.1 minutes and the reflow persistedfor20.0 ± 10.9 minutes. Peptide 6A administration also restored coronary blood flow (peak 20 ± 4 ml/ minute) in seven of eight animals with occlusive coronary thrombus. Mean time to blood flow restoration (4.3 ±2.9 minutes) wasshorter(P>0.05) than with rt-PA, but thereflow persisted only for the duration of tine infusion (16.3 ± 10.2 minutes).Peptide 6A adninistration was associatedwith a significant (P±0.05) increase in plasma 6-keto-PGF1α indicating stimulation of prostacyclin release. In addition, plasma t-PA concentrations also increased (F>0.01) at the peak effect of peptide 6A indicating releaseof endogenous t-PA as another potentialmechanism of the thrombolytic effects of peptide 6A. This study demonstrates that peptide 6A exerts coronary thrombolytic effectsccmpa rable to those of t-PA in a canine model of coronary thrombosis.

High-Dose of Epoietin Alfa in Patients with Low-Risk Myelodysplastic Syndromes (MDS): A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4703-4703 ◽  
Author(s):  
Giuseppe Mele ◽  
Clelia Musto ◽  
Rosella Matera ◽  
Maria Luigia Vigliotti ◽  
Alfredo Tartarone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Maintenance Treatment ◽  
Response Rate ◽  
Standard Dose ◽  
Initial Response ◽  
Mean Value ◽  
Low Risk ◽  
High Dose ◽  
Erythroid Hyperplasia ◽  
Significant Difference

Abstract Several studies showed that the response rate to standard dose of recombinant Human Erythropoietin (rHuEPO) in MDS patients is generally low, with only few cases presenting a significant increase of haemoglobin (Hb) levels. So, currently, the interest has focused on the use of high dose rHuEPO. The rationale for using high dose rHuEPO was elucidated: residual normal stem cells and/or abnormal clone of MDS stem cells, unresponsive to low levels of endogenous EPO, might respond to high doses of rHuEPO. The aim of this study was to assess the efficacy and safety of high dose rHuEPO treatment. EPO alfa 40.000 IU was given subcutaneously twice weekly for 4 weeks. Twenty-five patients with low-risk MDS (17 RA and 8 RARS) and Hb levels ≤ 10 g/dL were included in this study; sixteen patients were female and 9 male; mean age of enrolled patients was 74 years (range 66 – 85). Twenty-two of 25 patients completed the scheduled treatment and were evaluated for response. At 4 weeks eighteen of 22 patients (81%) showed a Hb mayor response (Hb increase ≥ 2 g/dL); Hb mean value at baseline was 8,15 g/dL (range 7 – 10), at 4 weeks was 13,15 g/dL (range 10 – 14,6). In 4 of 22 patients (19%) the high dose rHuEPO did not induce an increase of Hb levels after 4 weeks of treatment; in addition, these patients needed of RBC transfusions to maintain Hb levels ≥ 8 g/dL. The failure of treatment with rHuEPO occurred in patients with diagnosis of RARS. In our study there were no statistically significant differences between the group of patients with erythroid hyperplasia and the group of patients with normal percent of bone marrow erythroid cells (P = 0,4); no significant difference was noted in response rates between patients with RBC pre-treatment transfusion need and those with stable anaemia without prior transfusion (P = 0,09). In our study, Hb mayor response occurred also in one patient with marked marrow fibrosis. In this study all patients presented defective endogenous EPO production related to their degree of anaemia, with serum EPO levels ≤ 100 mU/ml (mean value 43,5; range 6 – 98). The responder patients need continuous maintenance treatment to maintain their response; EPO alfa 40.000 IU was given subcutaneously once a week; at 12 weeks overall response rate was 77%: 13/18 patients maintained their mayor response, 4/18 patients showed decreased Hb levels in comparison to initial response (Hb decrease > 1 < 2 g/dL), 1 patient progressed on RAEB. Hb mean value at 12 weeks was 11,8 g/dL (range 9,2 – 13,5). The median duration of maintenance of the erythroid response was 7,5 months (range 2 – 24 months). Treatment with high dose of rHuEPO is well tolerated; only one adverse event of arterial hypertension of moderate severity was reported as possible episode related to treatment. In conclusion, our study shows that, in low-risk MDS patients with defective endogenous EPO production, EPO alfa 40.000 IU, given subcutaneous twice weekly for 4 weeks, induces rapid, significant and persistent increase of Hb, without important adverse events; continuous maintenance treatment with 40.000 IU/w is necessary for the majority of the responding patients to maintain their response.

Impact of dose-escalated radiation on overall survival in men with nonmetastatic prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 28-28
Author(s):  
Anusha Kalbasi ◽  
Jiaqi Li ◽  
Abigail T. Berman ◽  
Samuel Swisher-McClure ◽  
Marc C. Smaldone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Standard Dose ◽  
Low Risk ◽  
External Beam Radiation ◽  
Risk Category ◽  
Beam Radiation ◽  
Treatment Groups

28 Background: Infive publishedRCTs, dose-escalated external beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, the question of whether dose escalation improves overall survival (OS) remains unanswered. We examined OS among men with non-metastatic prostate cancer undergoing EBRT in the modern era. Methods: Using the National Cancer Database (NCDB), we conducted non-randomized comparative effectiveness studies of dose-escalated versus standard-dose EBRT in men diagnosed from 2004-2006 in three analytic cohorts defined by NCCN risk category: low- (N=12,848), intermediate- (N=14,966) or high-risk (N=14,587) prostate cancer. We categorized patients in each risk cohort into 2 treatment groups: standard-dose (68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT. The primary outcome was time to death from any cause, measured from diagnosis to NCDB date of death or end of follow-up (December 31, 2011). We compared OS between treatment groups in the three analytic cohorts using Cox proportional hazard models. Inverse probability weighted propensity score methods were used to balance differences between treatment groups in age, race, year of diagnosis, AJCC T- and N-stage, PSA, Gleason score, androgen deprivation therapy, IMRT use, comorbid disease, income, insurance, urban/rural location, facility type and facility volume. In secondary analyses, we evaluated dose response for survival by categorizing dose in approximately 2 Gy increments. Results: Median follow up for survivors was between 73 and 74 months in all three risk cohorts. Dose-escalated EBRT was associated with improved survival in the intermediate-risk (adjusted HR 0.81, 95% CI 0.77 and 0.85, p<0.0001) and high-risk groups (aHR 0.85, 95% CI 0.81 and 0.89, p<0.0001), but not the low-risk group (aHR 0.99, 95% CI 0.92-1.06, p=0.803). For every incremental ~2Gy increase in dose, there was a 9% (95% CI 6% – 11%, p<0.0001) and 7% (95% CI 3% - 10%, p=0.004) reduction in the hazard of death for intermediate- and high-risk patients, respectively. Conclusions: Dose-escalated EBRT is associated with improved survival in men with intermediate- and high-risk, but not low-risk, prostate cancer.

scholarly journals Upfront therapy: the case for continuous treatment

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 55-58
Author(s):  
Constantine S. Tam
Keyword(s):  
High Risk ◽  
Initial Therapy ◽  
Continuous Treatment ◽  
Standards Of Care ◽  
Frontline Treatment ◽  
Upfront Therapy

Abstract Both BTKi and BCL2i are regarded as standards of care for frontline treatment of CLL. In this paper, I present the arguments for favoring BTKi as initial therapy. Venetoclax-based regimens have the advantage of being fixed in duration, but patients with select high-risk features may experience inferior PFS relative to those without high-risk features.

scholarly journals Personalized Management in Low-Risk Prostate Cancer: The Role of Biomarkers

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Siebren Dijkstra ◽  
Agus Rizal A. H. Hamid ◽  
Gisèle H. J. M. Leyten ◽  
Jack A. Schalken
Keyword(s):  
Prostate Cancer ◽  
Low Risk ◽  
Main Challenge ◽  
Aggressive Cancer ◽  
Slow Progression ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer ◽  
Progression Of Disease ◽  
Patients At Risk

Current criteria to predict low-risk prostate cancer (PCa) are still subject to discussion as a substantial number of PCa patients who progress to a more aggressive disease seem to be missed, using these criteria. The main challenge in PCa diagnosis, therefore, is to distinguish patients with low-risk PCa who will show slow progression of disease from patients at risk for progression to a more aggressive cancer. The current discovered biomarkers could potentially guide in this management and improve detection, staging, and prognosis. This paper provides an overview of the current available serum-, urine-, and tissue-based biomarkers in PCa and evaluates the clinical usefulness of these biomarkers in the detection and management of low-risk PCa.

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