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Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

ABSTRACT: BACKGROUND:Erythropoiesis-stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower "standard doses" (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking. METHODS:A cohort of 104 MDS patients treated with HD was retrospectively compared to 208 patients treated with SD in a propensity score-matched analysis to evaluate hematological improvement-erythroid (HI-E) rate induced by the different doses of rhEPO. The impact of rhEPO doses on survival and progression to leukemia was also investigated. RESULTS:Overall HI-E rate was 52.6%. No difference was observed between different rhEPO doses (P = .28) in matched cohorts; in a subgroup analysis, transfusion-dependent patients and patients with higher IPSS-R score obtained a higher HI-E rate with HD, although without significant impact on overall survival (OS). Achievement of HI-E resulted in superior OS. At univariate analysis, a higher HI-E rate was observed in transfusion-independent patients (P < .001), with a lower IPSS-R score (P < .001) and lower serum EPO levels (P = .027). Multivariate analysis confirmed that rhEPO doses were not significantly related to HI-E (P = .26). There was no significant difference in OS or progression to leukemia in patients treated with HD vs SD. CONCLUSION:SD are substantially equally effective to HD to improve anemia and influencing survival in MDS patients stratified according to similar propensity to be exposed to rhEPO treatment.

SUBMITTER: Balleari E

PROVIDER: S-EPMC6912022 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

Balleari Enrico E Filiberti Rosa Angela RA Salvetti Chiara C Allione Bernardino B Angelucci Emanuele E Bruzzone Marco M Calzamiglia Tullio T Cavaliere Marina M Cavalleri Maurizio M Cilloni Daniela D Clavio Marino M Crisà Elena E Da Col Anna A Danise Paolo P Pilo Federica F Ferrero Dario D Finelli Carlo C Gioia Daniela D Lemoli Roberto Massimo RM Masiera Elisa E Messa Emanuela E Miglino Maurizio M Musto Pellegrino P Natalie Oliva Esther E Poloni Antonella A Salvi Flavia F Sanna Alessandro A Scudeletti Marco M Tassara Rodolfo R Santini Valeria V

Cancer medicine 20191027 18

<h4>Background</h4>Erythropoiesis-stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower "standard doses" (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking.<h4>Methods</h4>A cohort of 104 MDS patients treated with HD w ...[more]

PMID: 31657156

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Project description:Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Patients could be red blood cell transfusion-dependent or not and were given epoetin zeta 40 000 IU/week. Serum erythropoietin level, iron parameters, hepcidin, flow cytometry Ogata and RED scores, and growth-differentiation factor-15 levels were determined at baseline, and molecular analysis by next-generation sequencing was also conducted. Erythroid response (defined according to the International Working Group 2006 criteria) was assessed at week 12. Seventy patients, with a median age of 78 years, were included in the study. There were 22 patients with refractory cytopenia with multilineage dysplasia, 19 with refractory cytopenia with unilineage dysplasia, 14 with refractory anemia with ring sideroblasts, four with refractory anemia with excess blasts-1, six with chronic myelomonocytic leukemia, two with del5q-and three with unclassifiable myelodysplastic syndrome. According to the revised International Prognostic Scoring System, 13 had very low risk, 47 had low risk, nine intermediate risk and one had high-risk disease. Twenty patients were transfusion dependent. Forty-eight percent had an erythroid response and the median duration of the response was 26 months. At baseline, non-responders had significantly higher RED scores and lower hepcidin:ferritin ratios. In multivariate analysis, only a RED score >4 (P=0.05) and a hepcidin:ferritin ratio <9 (P=0.02) were statistically significantly associated with worse erythroid response. The median response duration was shorter in patients with growth-differentiation factor-15 >2000 pg/mL and a hepcidin:ferritin ratio <9 (P=0.0008 and P=0.01, respectively). In multivariate analysis, both variables were associated with shorter response duration. Erythroid response to epoetin zeta was similar to that obtained with other erythropoiesis-stimulating agents and was correlated with higher baseline hepcidin:ferritin ratio and lower RED score. ClinicalTrials.gov registration: NCT 03598582.

Project description:Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid-related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating tumor necrosis factor-? and interleukin-1? production. The role of myelodysplastic syndrome-related inflammatory proteins in endogenous erythropoietin regulation and response to erythroid-stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro erythropoietin elaboration. Serum samples collected from 311 patients with myelodysplastic syndrome were investigated (125 prior to treatment with erythroid-stimulating agents and 186 prior to lenalidomide therapy). Serum concentrations of S100A9, S100A8, tumor necrosis factor-?, interleukin-1? and erythropoietin were analyzed by enzyme-linked immunosorbent assay. Using erythropoietin-producing HepG2 cells, we show that S100A9, tumor necrosis factor-? and interleukin-1? suppress transcription and cellular elaboration of erythropoietin. Pre-incubation with lenalidomide significantly diminished suppression of erythropoietin production by S100A9 or tumor necrosis factor-?. Moreover, in peripheral blood mononuclear cells from patients with myelodysplastic syndromes, lenalidomide significantly reduced steady-state S100A9 generation (P=0.01) and lipopolysaccharide-induced tumor necrosis factor-? elaboration (P=0.002). Enzyme-linked immunosorbent assays of serum from 316 patients with non-del(5q) myelodysplastic syndromes demonstrated a significant inverse correlation between tumor necrosis factor-? and erythropoietin concentrations (P=0.006), and between S100A9 and erythropoietin (P=0.01). Moreover, baseline serum tumor necrosis factor-? concentration was significantly higher in responders to erythroid-stimulating agents (P=0.03), whereas lenalidomide responders had significantly lower tumor necrosis factor-? and higher S100A9 serum concentrations (P=0.03). These findings suggest that S100A9 and its nuclear factor-?B transcriptional target, tumor necrosis factor-?, directly suppress erythropoietin elaboration in myelodysplastic syndromes. These cytokines may serve as rational biomarkers of response to lenalidomide and erythroid-stimulating agent treatments. Therapeutic strategies that either neutralize or suppress S100A9 may improve erythropoiesis in patients with myelodysplastic syndromes.

Project description:ObjectivesThe aim of this study is to compare the postoperative complications, perioperative course, and survival among patients from the multicentric Spanish Video-assisted Thoracic Surgery Group database who received video-assisted thoracic surgery lobectomy or video-assisted thoracic surgery anatomic segmentectomy.MethodsFrom December 2016 to March 2018, a total of 2250 patients were collected from 33 centers. Overall analysis (video-assisted thoracic surgery lobectomy = 2070; video-assisted thoracic surgery anatomic segmentectomy = 180) and propensity score-matched adjusted analysis (video-assisted thoracic surgery lobectomy = 97; video-assisted thoracic surgery anatomic segmentectomy = 97) were performed to compare postoperative results. Kaplan-Meier and competing risks method were used to compare survival.ResultsIn the overall analysis, video-assisted thoracic surgery anatomic segmentectomy showed a lower incidence of respiratory complications (relative risk, 0.56; confidence interval, 0.37-0.83; P = .002), lower postoperative prolonged air leak (relative risk, 0.42; 95% confidence interval, 0.23-0.78; P = .003), and shorter median postoperative stay (4.8 vs 6.2 days; P = .004) than video-assisted thoracic surgery lobectomy. After propensity score-matched analysis, prolonged air leak remained significantly lower in video-assisted thoracic surgery anatomic segmentectomy (relative risk, 0.33; 95% confidence interval, 0.12-0.89; P = .02). Kaplan-Meier and competing risk curves showed no differences during the 3-year follow-up (median follow-up in months: 24.4; interquartile range, 20.8-28.3) in terms of overall survival (hazard ratio, 0.73; 95% confidence interval, 0.45-1.7; P = .2), tumor progression-related mortality (subdistribution hazard ratio, 0.41; 95% confidence interval, 0.11-1.57; P = .2), and disease-free survival (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.35-1.51; P = .4) between groups.ConclusionsVideo-assisted thoracic surgery segmentectomy showed results similar to lobectomy in terms of postoperative outcomes and midterm survival. In addition, a lower incidence of prolonged air leak was found in patients who underwent video-assisted thoracic surgery anatomic segmentectomy.

Project description:BackgroundMaternal and newborn mortality rates in Ethiopia are among the highest in sub-Saharan Africa. The majority of deaths take place during childbirth or within the following 48 h. Therefore, ensuring facility deliveries with emergency obstetric and newborn care services available and immediate postnatal follow-up are key strategies to increase survival. In early 2014, the Family Conversation was implemented in 115 rural districts in Ethiopia, covering about 17 million people. It aimed to reduce maternal and newborn mortality by promoting institutional delivery, early postnatal care and immediate newborn care practices. More than 6000 Health Extension Workers were trained to initiate home-based Family Conversations with pregnant women and key household decision-makers. These conversations included discussions on birth preparedness, postpartum and newborn care needs to engage key household stakeholders in supporting women during their pregnancy, labor and postpartum periods. This paper examines the effects of the Family Conversation strategy on maternal and neonatal care practices.MethodsWe used cross-sectional data from a representative sample of 4684 women with children aged 0-11 months from 115 districts collected between December 2014 and January 2015. We compared intrapartum and newborn care practices related to the most recent childbirth, between those who reported having participated in a Family Conversation during pregnancy, and those who had not. Propensity score matched analysis was used to estimate average treatment effects of the Family Conversation strategy on intrapartum and newborn care practices, including institutional delivery, early postnatal and immediate breastfeeding.ResultsAbout 17% of the respondents reported having had a Family Conversation during their last pregnancy. Average treatment effects of 7, 12, 9 and 16 percentage-points respectively were found for institutional deliveries, early postnatal care, clean cord care and thermal care of the newborn (p?<?0.05).ConclusionWe found evidence that Family Conversation, and specifically the involvement of household members who were major decision-makers, was associated with better intrapartum and newborn care practices. This study adds to the evidence base that involving husbands and mothers-in-law, as well as pregnant women, in behavior change communication interventions could be critical for improving maternal and newborn care and therewith lowering mortality rates.

Dataset Information

Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

Publications

Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

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