Dataset Information

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

ABSTRACT:

Background

The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown.

Materials and methods

We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunosuppression, particularly with steroids.

Results

We found autoantibody positivity in 43% of cases and overt autoimmune diseases in 18%, including autoimmune hemolytic anemia, immune thromboctyopenia, and Evans syndrome. Steroid treatment improved cytopenia in about half of patients, with 26% achieving a complete recovery lasting for a median of 12 months. Better responses were observed in anemic patients with anti-erythrocyte autoantibodies than in those with anti-platelet autoantibodies, and the combination with recombinant erythropoietin (7/10) had a possible synergistic effect. Steroid doses were heterogeneous depending on the clinical intent (i.e., anti-inflammatory, immunosuppressive, anabolizing). Patients treated with a dose of 1 mg/kg day of prednisone for overt autoimmune cytopenia showed high rates of complete responses (60%).

Discussion

This observation suggests a trial with a short course (2-3 weeks) of standard steroid doses to ascertain efficacy and properly silence the autoimmune pathogenic mechanism. Steroid-related adverse events (16% of cases) should be monitored carefully in this elderly, frail population. In conclusion, features of autoimmunity are present in more than two-thirds of low-risk MDS patients and a trial with prednisone 0.5-1 mg/kg day for 2-3 weeks, with proper monitoring of adverse events, may be useful to improve cytopenias in selected cases.

SUBMITTER: Fattizzo B

PROVIDER: S-EPMC10497380 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

Fattizzo Bruno B Serpenti Fabio F Versino Francesco F Cassanello Giulio G Cro Lilla M LM Barbieri Marzia M Croci Giorgio A GA Revelli Nicoletta N Della Porta Matteo G MG Barcellini Wilma W

Blood transfusion = Trasfusione del sangue 20221222 5

<h4>Background</h4>The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown.<h4>Materials and methods</h4>We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunos ...[more]

PMID: 36580026

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Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. Low-risk MDS patients and age-matched controls without haematological malignancies were included in the study. Mononuclear cells were isolated from bone marrow samples of low-risk MDS patients and controls by density gradient (Ficoll). A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation and expression, while the whole series was used as a control group of expression data.

Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. Low-risk MDS patients and age-matched controls without haematological malignancies were included in the study. Mononuclear cells were isolated from bone marrow samples of low-risk MDS patients and controls by density gradient (Ficoll). A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation (using Methylated CpG Island Amplification and Microarrays, MCAM) and expression (using Affymetrix microarrays HG-U133 Plus 2), while the whole series was used as a control group of expression data.

Project description:The majority of myelodysplastic syndrome (MDS) patients belong to the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R) lower-risk categories. Their precise diagnostics and prognostic stratification is often a challenge, but may ensure the optimization of therapy. The availability of diverse treatment options has significantly improved the quality of life and survival of this group of patients. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk MDS, and may be treated successfully with erythropoietic stimulating agents, provided a careful selection is performed on the basis of IPSS-R, endogenous erythropoietin levels, and transfusion independence. Doses and duration of therapy of erythropoietic-stimulating agents (ESAs) are critical to determine efficacy. In case a patient fails ESA treatment, the available options may include lenalidomide (approved for del5q positive cases), hypomethylating agents, and a rather large number of experimental agents, whose clinical trials should be offered to a larger number of MDS patients. The choice for second-line treatment must take into account biologic, cytogenetic, and molecular-identified characteristics of individual patients, as well as frailty and comorbidities. Other cytopenias are less frequently presenting as isolated. Specific therapy for thrombocytopenia has been proposed in experimental clinical trials with thrombomimetic agents that have shown good efficacy, but raised some safety concern. Although neutropenia is targeted symptomatically with growth factor supportive care, the immunosuppressive treatments are indicated mainly for pancytopenic, hypoplastic lower-risk MDS; they are not widely used because of their toxicity, despite the fact that they may induce responses. Finally, hematopoietic stem cell transplant is the curative option also for lower-risk MDS and timing should be carefully evaluated, balancing toxicity and the possibility of survival advantage. Finally, even when considered suitable for lower-risk MDS, transplant application is limited to the rarer fit and younger MDS patient.

Dataset Information

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

Background

Materials and methods

Results

Discussion

Publications

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

Similar Datasets

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