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Myelodysplastic syndrome
Myelodysplastic syndrome (MDS) is a heterogeneous group of hematologic neoplasms defined as a clonal disorder of hematopoietic stem cells leading to dysplasia and ineffective hematopoiesis in the bone marrow
Prevalence
5-13 / 100,000
Age of Onset
ICD-10
D46.9
Inheritance
Myelodysplastic Syndrome (MDS) is primarily considered an acquired disorder and is not typically inherited through genetic transmission from parents to their children. However, there can be genetic factors that contribute to the development of MDS.
5 Facts you should know
FACT
A heterogeneous group of closely related clonal hematopoietic disorders commonly found in the aging population.
FACT
Signs and symptoms may include dizziness, fatigue, weakness, shortness of breath, bruising and bleeding, frequent infections, and headaches.
FACT
Patients with MDS may present with clinical manifestations of anemia, thrombocytopenia, and/or neutropenia.
FACT
Risk factors include previous chemotherapy or radiation therapy, exposure to tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead.
FACT
The typical age of onset is 70 years.
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Common signs & symptoms
Cytopenias:
MDS frequently presents with cytopenias, including anemia, thrombocytopenia, and neutropenia. Fatigue, pallor, and increased infection susceptibility are common due to reduced blood cell counts.
Macrocytic Anemia:
Macrocytic anemia, often refractory to iron treatment, is a hallmark of MDS. Reticulocytopenia might accompany this presentation.
Dysplastic Changes:
Dysplastic features in blood cell morphology, such as abnormal nuclear shapes and nuclear-cytoplasmic dyssynchrony, are observed in peripheral blood and bone marrow smears.
Bleeding Tendencies:
Thrombocytopenia and platelet dysfunction contribute to easy bruising, petechiae, and mucosal bleeding.
Risk of Leukemic Transformation:
MDS carries an inherent risk of progression to AML. Monitoring for increasing blasts in bone marrow and peripheral blood is crucial.
Symptoms of Aplastic Anemia:
MDS may mimic aplastic anemia, featuring severe pancytopenia and hypocellularity in the bone marrow.
Recognition of signs and symptoms indicative of Myelodysplastic Syndrome (MDS) is crucial for early diagnosis and appropriate patient care. Clinicians should be attentive to cytopenias, macrocytic anemia, dysplastic changes, bleeding tendencies, and the potential for leukemic transformation.
References:
Germing, U., et al. (2013). Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood, 122(17), 2943-2964.
Cazzola, M., & Malcovati, L. (2021). Myelodysplastic syndromes—coping with ineffective hematopoiesis. New England Journal of Medicine, 384(6), 542-554.
Bennett, J. M., et al. (2018). Diagnosis and management of myelodysplastic syndromes in adults: recommendations from the International Myelodysplastic Syndrome Working Group.
Leukemia, 32(10), 1718-1741.
Current treatments
Management of MDS requires a tailored approach based on disease risk, patient characteristics, and treatment goals. This summary outlines key treatment strategies for MDS, providing physicians with a comprehensive overview of available interventions.
Supportive Care:
- Blood Transfusions: Red blood cell and platelet transfusions help manage anemia and thrombocytopenia, respectively.
- Growth Factors: Erythropoiesis-stimulating agents (ESAs) and granulocyte colony-stimulating factors (G-CSFs) may be used to stimulate blood cell production.
- Infection Prevention: Prophylactic antibiotics and antifungal agents help reduce infection risk, especially in neutropenic patients.
Hypomethylating Agents:
Azacitidine and decitabine are DNA methyltransferase inhibitors that can induce hematologic improvement and delay progression to AML in higher-risk MDS.
Lenalidomide:
An immunomodulatory agent with activity in certain MDS subtypes, particularly with isolated del(5q) cytogenetic abnormality.
Immunosuppressive Therapy:
Antithymocyte globulin (ATG) with or without cyclosporine may benefit a subset of MDS patients with hypocellular bone marrow or autoimmune features.
Chemotherapy and Hematopoietic Stem Cell Transplantation (HSCT):
- Intensive chemotherapy followed by allogeneic HSCT is considered for fit patients with higher-risk MDS and an available donor.
- Conventional chemotherapy may be used in specific cases, but it's generally less preferred due to associated toxicities.
Supportive Measures:
- Erythropoiesis-stimulating agents (ESAs) and iron chelation therapy aid in managing anemia and iron overload, respectively.
- Growth factors may be beneficial in select cases.
Top Clinical Trials
| Title | Description | Phases | Status | Interventions | More Information |
|---|---|---|---|---|---|
| Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome | This study compares the efficacy of Tamibarotene in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms. | Phase 3 | Recruiting | Drug: Tamibarotene + Azacitidine|Drug: Tamibarotene Matched Placebo + Azacitidine | https://ClinicalTrials.gov/show/NCT04797780 |
| A Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With International Prognostic Scoring System Revised (IPSS-R) Low- or Intermediate-risk Myelodysplastic Syndrome (MDS) | The purpose of this study is to evaluate the safety and efficacy of oral azacitidine in participants with low to intermediate International Prognostic Scoring System Revised (IPSS-R) myelodysplastic syndrome (MDS). | Phase 2|Phase 3 | Recruiting | Drug: Oral Azacitidine|Drug: Placebo for Oral Azacitidine | https://ClinicalTrials.gov/show/NCT05469737 |
| Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) | The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion-dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Part 1 of the study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat to placebo in transfusion-dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Part 2 of the study. | Phase 2|Phase 3 | Recruiting | Drug: Imetelstat|Drug: Placebo | https://ClinicalTrials.gov/show/NCT02598661 |
| A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML | Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B) of ASTX030. Phase 2 is a randomized open-label crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of the study is expected to be approximately 48 months. | Phase 2|Phase 3 | Recruiting | Drug: Azacitidine|Drug: ASTX030 (cedazuridine + azacitidine)|Drug: Cedazuridine | https://ClinicalTrials.gov/show/NCT04256317 |
| A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials | A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept | Phase 3 | Recruiting | Drug: Luspatercept | https://ClinicalTrials.gov/show/NCT04064060 |
| Precision-T: A Randomized Phase III Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies | This study will compare the safety and efficacy between patients receiving an engineered donor graft ("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) or standard-of-care (SOC) control in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation (MA-alloHCT) for hematologic malignancies. This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685. | Phase 3 | Recruiting | Biological: Orca-T|Biological: Standard-of-Care | https://ClinicalTrials.gov/show/NCT05316701 |
Top Treatments in Research
| Agent | Class/Mechanism of Action | Development Status | Company | Clinical Studies | More Information |
|---|---|---|---|---|---|
| Tamibarotene | An oral selective retinoic acid receptor alpha (RARα) agonist developed for genomically defined subsets of patients whose disease is characterized by the overexpression of the RARA gene. When RARα is expressed in excess of its tightly controlled natural ligand, cells in the bone marrow may not differentiate into healthy myeloid cells, which can lead to hematological malignancies. Tamibarotene binds to RARα, allowing for the restoration of gene expression and myeloid differentiation. | Phase 3 | Syros Pharmaceuticals | https://ClinicalTrials.gov/show/NCT04797780 | https://www.syros.com/programs/tamibarotene |
| Oral Azacitidine | Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside present in DNA and RNA. It induces antineoplastic activity by inhibiting DNA methyltransferase at low doses and inducing cytotoxicity by incorporating itself into RNA and DNA at high doses. | Phase 2|Phase 3 | Bristol-Myers Squibb | https://ClinicalTrials.gov/show/NCT05469737 | https://ascopost.com/news/april-2021/oral-azacitidine-in-lower-risk-myelodysplastic-syndromes/ |
| Imetelstat | Imetelstat binds to telomerase and inhibits its activity, selectively killing the malignant stem and progenitor cells in the bone marrow that are the source of disease in blood cancers, such as myelodysplastic syndromes (MDS) and myelofibrosis (MF). | Phase 2|Phase 3 | Geron Corporation | https://ClinicalTrials.gov/show/NCT02598661 | https://www.geron.com/research-and-development/imetelstat/ |
| ASTX030 (cedazuridine + azacitidine) | ASTX030 is an investigational oral formulation of azacitidine + cedazuridine designed to enhance systemic bioavailability of azacitidine delivered orally to the level achieved with parenteral administration of azacitidine alone. Cedazuridine is a cytidine deaminase inhibitor and inhibits azacitidine inactivation in the gut and liver. | Phase 2|Phase 3 | Astex Pharmaceuticals, Inc. | https://ClinicalTrials.gov/show/NCT04256317 | https://astx.com/azacitidine-and-cedazuridine-astx030-oral-dnmt-inhibitor-hematological-malignancies/ |