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Myelodysplastic Syndromes

Clonal hematopoietic stem cell disorders causing ineffective hematopoiesis, cytopenias, dysplasia, macrocytosis, and risk of AML transformation

Review date
reviewed 2026-05-04
Reading time
8 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Hematology & Oncologyless-commonlong-term-condition
On this page
Condition details
Hematology & Oncology
less-common
8 min read
reviewed 2026-05-04
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About This Page

This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

  • MDS presents in older adults with unexplained cytopenias, often macrocytic anemia
  • Peripheral smear may show dysplastic neutrophils, hypogranulation, pseudo-Pelger-Huet cells, or abnormal platelets
  • Bone marrow is usually hypercellular with ineffective hematopoiesis
  • MDS can transform to AML; risk depends on cytogenetics, blasts, and depth of cytopenias
  • Treatment ranges from supportive transfusions and growth factors to hypomethylating agents and allogeneic transplant

Overview

Myelodysplastic syndromes are clonal marrow disorders characterized by ineffective and dysplastic blood cell production. Despite a cellular marrow, peripheral cytopenias occur because abnormal precursors undergo apoptosis or fail to mature properly. MDS may be de novo or therapy-related after chemotherapy/radiation.

Epidemiology

MDS primarily affects older adults. Risk factors include advanced age, prior chemotherapy or radiation, benzene exposure, smoking, inherited marrow failure syndromes, and clonal hematopoiesis. Therapy-related MDS often has high-risk cytogenetics and poorer prognosis.

Clinical Features

Symptoms
Fatigue and dyspnea from anemia
Recurrent infections from neutropenia
Easy bruising, petechiae, mucosal bleeding from thrombocytopenia
Often found incidentally as macrocytic anemia
Signs
Pallor, petechiae, ecchymoses
Fever or infection signs if neutropenic
Usually no massive splenomegaly; prominent splenomegaly suggests MPN or other disorder

Investigations

First-line
CBC with differential and reticulocyte countOne or more cytopenias; macrocytosis common; retic count low
Peripheral smearDysplastic neutrophils, pseudo-Pelger-Huet cells, hypogranulation, abnormal platelets
B12, folate, iron studies, TSH, liver testsExclude reversible causes of macrocytosis and cytopenias
Second-line
Bone marrow biopsy and aspirateRequired for diagnosis; dysplasia, cellularity, blasts, ring sideroblasts
Cytogenetics/FISH/molecular testingRisk stratification and treatment selection
Erythropoietin levelHelps predict response to erythropoiesis-stimulating agents
Specialist
IPSS-R/IPSS-M risk stratificationCombines cytopenias, blasts, cytogenetics, and mutations to guide therapy

Management

NCCN Guidelines for Myelodysplastic Syndromes
1
Lower-risk disease
  • Supportive care: RBC and platelet transfusions as needed
  • Erythropoiesis-stimulating agents when symptomatic anemia and EPO level predicts response
  • Luspatercept for selected ring sideroblast/SF3B1-mutated disease
  • Iron chelation may be considered in chronically transfused selected patients
2
Higher-risk disease
  • Hypomethylating agents such as azacitidine or decitabine
  • Allogeneic stem cell transplant is the only potentially curative therapy for eligible patients
  • Clinical trial enrollment is often appropriate
3
Infection and bleeding prevention
  • Treat neutropenic fever urgently with broad-spectrum antibiotics
  • Avoid unnecessary myelosuppressive medications
  • Vaccination and supportive care tailored to immune status

Complications

  • AML transformation: Risk rises with higher blasts and adverse genetics
  • Transfusion dependence: Iron overload and alloimmunization
  • Severe infection: Neutropenia and dysfunctional neutrophils
  • Bleeding: Thrombocytopenia and platelet dysfunction
USMLE Step 2 CK Exam Tips
  • 1Older adult + macrocytic anemia + normal B12/folate = think MDS
  • 2Pseudo-Pelger-Huet cells and hypogranular neutrophils suggest dysplasia
  • 3Bone marrow biopsy is needed for diagnosis
  • 4MDS marrow is often hypercellular despite peripheral cytopenias
  • 5Therapy-related MDS after alkylating chemo or radiation has poor prognosis
  • 6MDS can transform to AML

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Verified Sources & References

NCCN Clinical Practice Guidelines in Oncology
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