Erythroid response (ER) rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa (EPO): A meta-analysis using the International Working Group criteria (IWGc) for MDS response

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6572-6572
Author(s):  
V. Moyo ◽  
P. Lefebvre ◽  
M. S. Duh ◽  
A. Bourezak ◽  
B. Yektashenas ◽  
...  
Keyword(s):  
Data Extraction ◽  
Meta Analysis ◽  
Refractory Anemia ◽  
Regression Analyses ◽  
Epoetin Alfa ◽  
Erythroid Response ◽  
Serum Erythropoietin Level ◽  
Study Characteristics ◽  
Serum Erythropoietin ◽  
Erythropoietin Level

6572 Background: Refractory anemia is a clinical hallmark of MDS. The most consistently used therapy for this anemia is EPO. Prior to the introduction of IWGc in 1997, ER rates varied substantially between studies. The present meta-analysis was undertaken to compare ER rates in studies of EPO-treated patients in MDS when defined by either IWGc or non-IWGc. Methods: A systematic review and data extraction of studies published from 1990–2005 in MDS patients treated with EPO was performed and yielded 21 studies evaluating a total of 895 patients. Pooled estimates of ER rates, stratified by IWGc, were calculated using random-effects meta-analysis methods, which incorporated both between- and within-study variations. Univariate meta-regression analyses were conducted to identify study characteristics that were significant determinants of ER rate. Results: Ten studies (604 patients) used the IWGc to define ER (overall, major, minor), while 11 studies (291 patients) used other definitions. Mean age for all patients was 70.6 years; 45% women. Mean baseline (BL) serum erythropoietin level and proportion of patients with refractory anemia or refractory anemia with ringed sideroblasts were comparable between studies; however, the proportion of transfusion-dependent patients at BL was lower in the IWG studies vs the non-IWG studies (36% vs. 84%, respectively, p<.001). The pooled estimate of ER rate was significantly higher for the IWG studies compared to the non-IWG studies (50.5%, 95% CI: 38.6%-62.3% vs. 27.8%, 95% CI: 22.7%-32.8% respectively, p=.002). Among patients in the IWG studies who achieved an ER, 62% (188/305) achieved a major ER. Studies reporting mean BL serum erythropoietin level <400mU/mL, <65% of patients transfusion-dependent at BL and use of subcutaneous EPO were found to be associated with higher ER rates. Conclusions: This meta-analysis of MDS patients treated with EPO demonstrates significantly higher ER rates in studies utilizing IWGc. These findings may be due to more refined definitions of ER and MDS diagnostic criteria as well as improvement in the management of anemia. [Table: see text]

Higher Erythroid Response Rates with Epoetin Alfa Versus Other Agents in Treatment-Naïve Low/Int-1 Myelodysplastic Syndrome Patients: A Comparative Meta-Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5074-5074
Author(s):  
Suneel Mundle ◽  
Patrick Lefebvre ◽  
Francis Vekeman ◽  
Mei Sheng Duh ◽  
François Laliberté ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Random Effect ◽  
Single Agent ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Risk Category ◽  
Epoetin Alfa ◽  
Agent Based ◽  
Demethylating Agent ◽  
Erythroid Response

Abstract Background: The treatment of newly diagnosed low/intermediate-1 (low/int-1) myelodysplastic syndromes (MDS) varies significantly from observation only (until the patient develops transfusion dependence) to using specific agents like erythropoiesis-stimulating (ESA), demethylating, or immunomodulatory (IMiD) agents. To date no prospective comparative clinical trial has been conducted to evaluate relative efficacy of these agents. In the present literature meta-analysis, we compared the erythroid response (ER) rates achieved with epoetin alfa (EPO)-based therapy (monotherapy or in combination with other growth factors or non-ESAs) versus single agent/combination non-ESA therapies for the treatment of anemia in patients with MDS and specifically in low/int-1 risk category. Methods: Data extraction was performed on studies from PubMed and ASCO/ASH proceedings in MDS patients treated with EPO ± granulocyte-/granulocyte-macrophage colony stimulating factor (G/GM-CSF) or other non-ESAs (search cutoff date 9/30/07). To allow cross comparison, only studies using IWG or IWG-like ER criteria and treatment-naïve patients were selected. Patients were further stratified according to risk and non-ESA therapy. Pooled estimates of ER rates were calculated using random-effect (R-E) meta-analysis methods. Results: Of 790 studies identified, 37 were included in the present analysis. Among the 23 studies that included low/int-1 MDS patients, a majority of the patients in both the EPO-based (82.4%) and non-ESA (74.4%) groups had refractory anemia or refractory anemia with ringed sideroblasts, and baseline transfusion dependency rates were lower in the EPO-based (52.4%) than in the non-ESA (91.7%) groups. As shown in the Table, among all MDS patients regardless of risk category, EPO-based regimens had a higher ER rate when compared to IMiD-based therapies (p=0.0328), or demethylating agent-based therapies (p=0.1660). In the patients with low/int-1 risk disease, EPO-based therapy had a significantly better ER rate when compared to single-agent/combination non-ESA-based therapies (p=0.0015) and specifically, IMiD-based therapies (p=0.0231). The studies with demethylating agent-based therapies in the present analysis did not include low/int-1 MDS patients. Conclusions: These results suggest that, for appropriately selected treatment-naïve patients with low/int-1 MDS, among the currently available therapies, EPO-based regimens may yield a higher erythroid response than non-ESA therapies, with lenalidomide in del 5q patients being the only exception. Further prospective clinical trials are needed to determine relative clinical benefits with different agents in different MDS risk groups. Non-ESA based therapy MDS Study Group EPO-based therapy All mono + combination therapies IMiD-based therapy Demethylating agent-based therapy NA: not available No. of Studies All 19 18 9 2 Low/Int-1 Risk 14 9 4 NA Evaluable patients, n All 849 866 635 85 Low/Int-1 Risk 620 403 291 NA Overall ER, R-E% (95% CI) All 56.7 (49–65) 33.6 (23–44) 39.3 (26–53) 37.6 (12–63) Low/Int-1 Risk 53.8 (46–62) 35.1 (24–46) 42.4 (37–48) NA

Erythroid Response (ER) Rates in Myelodysplastic Syndromes (MDS) Patients Treated with Epoetin Alfa (EPO) or Darbepoetin Alfa (DARB) Using International Working Group Response Criteria (IWGc): Comparative Meta-Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2672-2672 ◽  
Author(s):  
Suneel Mundle ◽  
Patrick Lefebvre ◽  
Mei S. Duh ◽  
Ahmed Bourezak ◽  
Behin Yektashenas ◽  
...  
Keyword(s):  
Patient Selection ◽  
Data Extraction ◽  
Meta Analysis ◽  
Evaluation Methods ◽  
Refractory Anemia ◽  
Weekly Dose ◽  
Minor Response ◽  
Erythroid Response ◽  
Significant Difference ◽  
Baseline Characteristics

Abstract Background: EPO has been used in the treatment of refractory anemia in MDS patients for many years. Recently, with the identification of definitive patient selection criteria (low serum EPO [sEPO] levels and receipt of minimal transfusions) and standardization of ER rate evaluation methods using the IWGc, response to EPO therapy has been shown to be significantly enhanced in low/int-1 risk MDS patients. The present meta-analysis was conducted to compare ER rates (defined as major + minor response) of the two erythropoiesis-stimulating therapies (ESTs) currently available in the US, EPO and DARB, in MDS patients who were selected and evaluated for ER using the aforementioned uniform criteria. Methods: A systematic review and data extraction of studies from PubMed and ASCO/ASH proceedings from 1990–2006 in MDS patients treated with EPO monotherapy and from 2003–2006 in those treated with DARB monotherapy was performed. Pooled estimates of ER rates were calculated in each group using random-effects meta-analysis methods, which incorporated both between- and within-group variations. Multivariate meta-regression analysis was further conducted to control for differences in baseline characteristics between the two groups. Results: Nine EPO studies (N=619 patients, N evaluable for ER rate =589) and 8 DARB studies (N=442, N evaluable for ER rate =389) were identified. Baseline characteristics were comparable between the two groups with respect to age, gender, mean baseline hemoglobin, transfusion dependency rates, and proportion of patients with refractory anemia/refractory anemia with ringed sideroblasts. The mean baseline sEPO levels were significantly higher in the EPO group, compared to the DARB group (376: range 43–418; vs. 133: range 68–303 mU/mL, p=0.0026). The average initial weekly dose in the EPO studies was 47,851 (range: 30,000–80,000) Units, while that in the DARB studies was 176 (range: 100–315) mcg. There was no significant difference in the pooled estimate of the ER rates for either EST (57.6%: 95% CI; 45–70) for the EPO studies vs. (59.4%: 95% CI; 49–70) for the DARB studies, (p=0.8282). Further, as compared to the studies with standard doses of the two ESTs per week (EPO 30,000–40,000 Units; DARB ≤ 150 mcg), those using higher doses of EPO (60,000–80,000 Units) or DARB (>150 mcg) per week showed significantly higher ER rates (EPO- 47.8% vs. 63.3%, p<0.001; DARB −52.6% vs. 71.1%, p<0.001). Conclusions: This current meta-analysis demonstrates that, with the use of standardized patient selection and response evaluation methods, the two clinically available ESTs yield comparable ER rates in MDS patients.

scholarly journals Saphenous Vein Graft Disease Is Associated with a Low Serum Erythropoietin Level

2015 ◽  
Vol 24 (6) ◽  
pp. 544-547 ◽  
Author(s):  
Ibrahim Kocaoglu ◽  
Ugur Arslan ◽  
Yavuzer Koza ◽  
Mustafa M�cahit Balci ◽  
Gizem �elik ◽  
...  
Keyword(s):  
Saphenous Vein ◽  
Vein Graft ◽  
Saphenous Vein Graft ◽  
Vein Graft Disease ◽  
Serum Erythropoietin Level ◽  
Graft Disease ◽  
Serum Erythropoietin ◽  
Saphenous Vein Graft Disease ◽  
Erythropoietin Level ◽  
Low Serum

scholarly journals THE RELATIONSHIP OF SERUM ERYTHROPOIETIN LEVEL WITH CORONARY COLLATERAL DEVELOPMENT

2010 ◽  
Vol 55 (10) ◽  
pp. A153.E1439
Author(s):  
Asife Sahinarslan ◽  
Ridvan Yalcin ◽  
Sinan Kocaman ◽  
Salih Topal ◽  
Ugur Ercin ◽  
...  
Keyword(s):  
Collateral Development ◽  
Coronary Collateral ◽  
Serum Erythropoietin Level ◽  
Relationship Of ◽  
The Relationship ◽  
Serum Erythropoietin ◽  
Erythropoietin Level

scholarly journals The role of serum erythropoietin level andjak2v617f allele burden in the diagnosis of polycythaemia vera

2014 ◽  
Vol 167 (3) ◽  
pp. 411-417 ◽  
Author(s):  
Àgueda Ancochea ◽  
Alberto Álvarez-Larrán ◽  
Cristian Morales-Indiano ◽  
Francesc García-Pallarols ◽  
Luz Martínez-Avilés ◽  
...  
Keyword(s):  
Polycythaemia Vera ◽  
Allele Burden ◽  
Serum Erythropoietin Level ◽  
Serum Erythropoietin ◽  
Erythropoietin Level

Serum erythropoietin level in anemic cancer patients

1999 ◽  
Vol 35 ◽  
pp. S105
Author(s):  
M. Özgüroglu ◽  
G. Demir ◽  
F. Demirelli ◽  
N. Molinas-Mandel ◽  
E. Büyükünal ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Serum Erythropoietin Level ◽  
Serum Erythropoietin ◽  
Erythropoietin Level

Treatment of Anemia with Darbepoetin Alfa in Patients with Low and Intermediate-1 Risk Myelodysplastic Syndromes. Results from the ARAMYS Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3451-3451
Author(s):  
Ana Villegas ◽  
B. Arrizabalaga ◽  
C. Fernández-lago ◽  
M. Mouzo ◽  
Jr Mayans ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Myelodysplastic Syndromes ◽  
Darbepoetin Alfa ◽  
Refractory Anemia ◽  
Fixed Dose ◽  
Baseline Serum ◽  
Erythroid Response ◽  
Transfusion Requirements ◽  
Baseline Values ◽  
Serum Erythropoietin

Abstract Anemia is the main symptom in patients (pts) with myelodysplastic syndromes (MDS) which usually makes subjects with this pathology dependent on transfusions, resulting in a very limited quality of life. Darbepoetin alfa (DA) is a highly glycosylated erythropoiesis-stimulating agent (ESA) with a pharmacokinetic profile that includes a longer serum half-life and allows it to be administered less frequently than rHuEPO, thereby increasing patient convenience. This single-arm, open-label, multi-center, phase 2 study evaluated the efficacy and safety of DA in pts with low risk MDS. Eligible pts had low or intermediate-1 risk MDS [International Prognostic Scoring System (IPSS) criteria], anemia [Hemoglobin (Hb) 10 g/dL], FAB (French–American–British) classification of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) (with marrow blasts ≤ 10%), serum erythropoietin levels < 500 IU/L and transfusion requirements < 2 packed red blood cells cells/month over the preceding 2 months. Pts were evaluated for erythroid response after 8 weeks (wks) and 16 wks of treatment. Major erythroid response (MaR) was defined as an increase in Hb values ≥2 g/dl on baseline values and/or suppression of transfusion requirements. A minor erythroid response (MiR) was defined as a > 1 g/dL increase in Hb values but < 2 g/dl on baseline values or a reduction in transfusion requirements of at least 50%. DA treatment was initiated at a fixed dose of 300 mcg weekly (QW). For pts achieving a MaR at wk 8, DA could be administered at the same dose every two wks (Q2W). For pts who did not achieve a MaR by 8 weeks, filgrastim 300 mcg QW was added for an additional 8 wks. If at any time during the treatment period Hb values of > 12g/dL were obtained, DA was discontinued until Hb falls to values of < 11 g/dL. At this time, DA treatment was reintroduced with half of the previous dose (150 mcg). A number of 44 evaluable pts were included in the study. Median age 75, 8 years (range 41, 3–92, 4), 53, 5% male and 90,7% with ECOG Performance Status (0–1). FAB diagnoses were 30,2% RA, 62,8% RARS and 7% RAEB; divided into IPSS low (76,7%) and intermediate-1 (23,3%). Baseline mean (SD) Hb was 9,2 g/dL (0.8) and serum erythropoietin 122,1 IU/L (124,7).72,7% of the pts were transfusion independent. An erythroid response was achieved by 31 of 44 pts (70,5%) at wk 8 (43,2% MaR, 27,3% MiR, 29,5% no response) and by 30 of 43 pts (69,8%) at week 16 (51,2% MaR, 18,6% MiR, 30,2% no response). A total of 19 pts received filgrastim between wk 8 and 16. Erythroid response at wks 8 and 16 depending on the transfusion dependence were 68,8% (59,1% MaR and 40,9% MiR) and 71.0% (68,2% MaR and 31,8% MiR) in the transfusion independent group and 75.0% (66,7% MaR and 33,7% MiR) and 66,70% (87,5% MaR and 12,5% MiR) in the transfusion dependent group. Baseline serum erythropoietin levels were the only predictive factor of response found in the study population. DA was generally well tolerated. Three mild adverse events were considered related to DA (iron deficiency, flu syndrome and headache), one severe (iron deficiency) and one fatal (thromboembolic event). Results from this study indicate that a fixed dose of 300 mcg DA QW (+/− filgrastim) is an effective and well-tolerated treatment of anemic patients with low- and intermediate-1 risk MDS.

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