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Management of patients with lower-risk myelodysplastic syndromes.

ABSTRACT: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis with abnormal blood cell development (dysplasia) leading to cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Patients with MDS can generally be classified as lower- (LR-MDS) or higher-risk (HR-MDS). As treatment goals for patients with LR-MDS and those with HR-MDS differ significantly, appropriate diagnosis, classification, and follow-up are critical for correct disease management. In this review, we focus on the diagnosis, prognosis, and treatment options, as well as the prediction of the disease course and monitoring of treatment response in patients with LR-MDS. We discuss how next-generation sequencing, increasing knowledge on mechanisms of MDS pathogenesis, and novel therapies may change the current treatment landscape in LR-MDS and why structured assessments of responses, toxicities, and patient-reported outcomes should be incorporated into routine clinical practice.

SUBMITTER: Brunner AM

PROVIDER: S-EPMC9751093 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Management of patients with lower-risk myelodysplastic syndromes.

Brunner Andrew M AM Leitch Heather A HA van de Loosdrecht Arjan A AA Bonadies Nicolas N

Blood cancer journal 20221214 12

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis with abnormal blood cell development (dysplasia) leading to cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Patients with MDS can generally be classified as lower- (LR-MDS) or higher-risk (HR-MDS). As treatment goals for patients with LR-MDS and those with HR-MDS differ significantly, appropriate diagnosis, classification, and ...[more]

PMID: 36517487

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Project description:Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.

Dataset Information

Management of patients with lower-risk myelodysplastic syndromes.

Publications

Management of patients with lower-risk myelodysplastic syndromes.

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