Myelodysplastic syndrome

Myelodysplastic syndrome
The Armed Forces Institute of Pathology (AFIP) · Public domain · source
Name	Myelodysplastic syndrome
Synonyms	MDS
Field	Hematology, Oncology

Myelodysplastic syndrome is a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and increased risk of progression to acute myeloid leukemia. It primarily affects older adults and is managed by hematologists using supportive care, disease-modifying agents, and allogeneic hematopoietic stem cell transplantation. Research into molecular genetics, chromosomal abnormalities, and patient-centered outcomes has shaped modern approaches to diagnosis and therapy.

Signs and symptoms

Patients typically present with symptoms related to anemia, thrombocytopenia, and neutropenia, such as fatigue, pallor, easy bruising, and recurrent infections. Clinical manifestations often overlap with conditions seen by specialists at Mayo Clinic, Johns Hopkins Hospital, Dana–Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Cleveland Clinic, prompting consultation with hematologists and oncologists. Physical findings may include pallor, petechiae, splenomegaly, or signs that trigger referral to centers like Massachusetts General Hospital, Mount Sinai Hospital (Manhattan), Guy's Hospital, Karolinska University Hospital, and Royal Marsden Hospital. Symptom burden drives quality-of-life assessments used in comparative effectiveness studies conducted by agencies such as the National Institutes of Health, Food and Drug Administration, and European Medicines Agency.

Causes and pathophysiology

Etiology involves acquired somatic mutations in hematopoietic stem cells, chromosomal abnormalities such as deletions of 5q and monosomy 7, and exposure-related risks including prior cytotoxic chemotherapy and radiotherapy used at institutions like Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center. Molecular drivers include mutations in genes frequently studied in labs at Cold Spring Harbor Laboratory, Broad Institute, and Wellcome Sanger Institute, including alterations in spliceosome components, epigenetic regulators, and signaling pathways. Pathophysiology features ineffective erythropoiesis and dysplasia in erythroid, myeloid, and megakaryocytic lineages, with clonal evolution described in seminal meetings such as the American Society of Hematology annual meeting and guidelines from the European Hematology Association. Environmental and occupational exposures investigated by agencies like the World Health Organization and Centers for Disease Control and Prevention have been implicated in some cases.

Diagnosis

Diagnosis relies on complete blood counts, peripheral blood smear review, bone marrow aspiration and biopsy, cytogenetic analysis, and molecular testing performed at reference laboratories including Quest Diagnostics, Laboratory Corporation of America, and academic centers like Stanford Health Care. Flow cytometry and fluorescence in situ hybridization are used alongside next-generation sequencing panels developed at the Broad Institute and commercial vendors to identify prognostic mutations. Diagnostic criteria and reporting follow standards promulgated by organizations such as the World Health Organization and the International Consensus Classification and are incorporated into practice at hospitals like Hospital of the University of Pennsylvania and Royal Free Hospital. Differential diagnosis includes aplastic anemia and vitamin deficiency states evaluated in clinics like Cleveland Clinic and Karolinska University Hospital.

Classification and subtypes

Classification schemes have evolved from French–American–British criteria to World Health Organization categories and the International Consensus Classification, with subtypes defined by blast percentage, cytogenetics, and lineage dysplasia. Entities such as MDS with isolated del(5q), MDS with excess blasts, and MDS with ring sideroblasts are distinguished in hematology textbooks used at Oxford University Press, Elsevier, and Springer Nature and in consensus reports from the American Society of Hematology and European LeukemiaNet. Subtype assignment guides therapeutic decisions at treatment centers like MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and Mayo Clinic.

Treatment and management

Management strategies range from supportive care—red blood cell transfusions, platelet transfusions, and growth factors—to disease-modifying agents such as hypomethylating agents, lenalidomide for 5q-deleted cases, and targeted therapies emerging from trials led by cooperative groups like the Cancer and Leukemia Group B and EORTC. Allogeneic hematopoietic stem cell transplantation remains the only curative option and is performed at transplant centers including Fred Hutchinson Cancer Center, Dana–Farber/Brigham and Women’s Cancer Center, and Hôpital Saint-Louis. Treatment decisions incorporate risk stratification tools such as the Revised International Prognostic Scoring System used by clinicians at Johns Hopkins Hospital, Mayo Clinic, and international guideline panels at the National Comprehensive Cancer Network. Supportive care frameworks draw on transfusion protocols from blood services like the American Red Cross and infection prophylaxis practices informed by the Infectious Diseases Society of America.

Prognosis and epidemiology

Prognosis varies by age, cytogenetics, blast percentage, and molecular features; survival ranges from months to many years with current therapies studied in registries maintained by entities like the Surveillance, Epidemiology, and End Results Program, European Haematology Association Registry, and institutional cohorts at Mayo Clinic and Memorial Sloan Kettering Cancer Center. Incidence increases with age and is influenced by prior chemotherapy exposures and occupational factors examined by the National Institute for Occupational Safety and Health. Clinical outcomes and health economics are subjects of research at organizations such as the National Cancer Institute and Institute for Health Metrics and Evaluation.