Myelodysplastic syndromes

Disease Description (Causes and Symptoms)

Myelodysplastic syndromes (MDS) are a group of disorders in which genetic and molecular abnormalities in the bone marrow (hematopoietic tissue) impair the differentiation and maturation of hematopoietic stem cells, resulting in reduced numbers and morphological abnormalities (dysplasia) in one or more cell lines (red blood cells, white blood cells, and platelets) in the peripheral blood.
Key pathophysiological features: gene mutations in bone marrow cells (e.g., SF3B1, TET2, ASXL1, TP53), chromosomal abnormalities, and ineffective hematopoiesis in the bone marrow → reduced peripheral blood cell counts and accumulation of excess blasts (abnormal precursor cells) in the bone marrow. Some patients progress over time to acute myeloid leukemia (AML, bone marrow blasts ≥20%) (estimated at approximately 10–40%).
Common symptoms: fatigue, malaise, and shortness of breath (anemia); frequent infections and fever (neutropenia or impaired neutrophil function); easy bruising or bleeding (thrombocytopenia); sometimes discovered incidentally through blood tests without symptoms. Age-related onset (mainly ages 50–90, with a male predominance). Secondary MDS may develop after previous chemotherapy or radiation therapy.

Treatment

The goals of treatment are symptom management (reducing anemia, infections, and bleeding), suppressing disease progression, and, when possible, achieving a cure (allogeneic hematopoietic stem cell transplantation). Treatment is individualized according to the patient's age, comorbidities, and risk level (IPSS/IPSS-R, bone marrow blast percentage, and chromosomal/molecular abnormalities).

• Conservative and supportive care

  • Red blood cell and platelet transfusions (as needed); management of transfusion dependence (monitoring for iron overload and considering iron chelation therapy [e.g., deferasirox])
  • Prompt antibiotic treatment for infections; use of G-CSF for severe neutropenia (depending on the situation)
  • Bleeding management: transfusions, local hemostasis, and, when necessary, consideration of antifibrinolytic agents (e.g., tranexamic acid)
  • Vaccination (inactivated vaccines are recommended; avoid live vaccines when immunocompromised)

• Lower-risk group (focused on symptom relief)

  • Erythropoiesis-stimulating agents (ESAs: epoetin, darbepoetin) — effective in some patients with anemia who meet specific criteria
  • Immunosuppressive therapy (antithymocyte globulin + cyclosporine) — effective in some younger patients and in certain phenotypes
  • Lenalidomide — high response rates in patients with del(5q) abnormalities
  • Luspatercept — used for anemia in lower-risk MDS with ring sideroblasts (including serum iron)

• Higher-risk group (for disease suppression and prolongation of survival)

  • Hypomethylating agents: azacitidine, decitabine — prolong survival and delay progression to AML
  • Targeted therapy: inhibitors for specific mutations (e.g., IDH1/2), when applicable
  • Clinical trials are recommended (there are many new drugs and combination therapies)

• Definitive treatment (with curative intent)

  • Allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) — the only potentially curative treatment, depending on age, comorbidities, and donor availability

• Other considerations

  • Treatment decisions should take into account the IPSS-R (revised risk score), molecular genetic testing, the patient's quality of life, and treatment goals
  • Regular blood tests, bone marrow examinations, monitoring for iron overload, and management of complications

Checklist Before an Outpatient Visit (Including Preparation Items and Example Questions)

Preparation items (bringing these can make the consultation more efficient)

• Recent complete blood count (CBC) results and previous test values (if possible, organized by date)
• Bone marrow examination (bone marrow biopsy) reports, and cytogenetic and molecular genetic test reports
• List of medications currently being taken (including prescriptions, OTC medications, and supplements) and allergy history
• Records of previous transfusions, infections, and hospitalizations; history of previous chemotherapy or radiation therapy
• Symptom records (the timing, frequency, and severity of fatigue, bleeding, fever, shortness of breath, etc.)
• Information about lifestyle habits (smoking, alcohol use, occupational exposures, etc.)

Examples of questions to briefly write down for the consultation (to provide to the medical team)

• The meaning of recent CBC values and the reasons for changes
• The goal of the currently proposed treatment options (symptom relief vs. prolonged survival vs. cure)

General Examples of Questions to Ask the Doctor

• How was the risk level (IPSS-R) of this disease assessed, and what is my prognosis?
• What are the recommended treatment options and the expected benefits and side effects of each?
• What are the indications for bone marrow transplantation (allogeneic hematopoietic stem cell transplantation), and is it appropriate for me? What are the expected complications and mortality rate?
• I need transfusions frequently; how should iron overload be managed? Do I need iron chelation therapy?
• What precautions should I take in daily life to reduce the risk of infection and bleeding?

Examples of Disease-Specific Questions

• What are my chromosomal abnormalities (e.g., del(5q), copy-number abnormalities, etc.) or molecular mutations (SF3B1, TP53, etc.)? How might these affect treatment selection (e.g., lenalidomide or targeted therapy) or prognosis?
• My anemia and thrombocytopenia are currently severe. What first-line treatment (ESA, hypomethylating agent, transplantation, etc.) is appropriate for me? Can treatment reduce my transfusion dependence?

Additional Information

• If symptoms worsen (severe bleeding, high fever or signs of shock, sudden severe shortness of breath, etc.), immediate evaluation in an emergency department is necessary.
• Treatment selection is determined by considering the individual's risk level, goals (maintaining quality of life vs. attempting a cure through intensive treatment), age, and comorbidities as a whole. Participating in a clinical trial may be a good way to access new treatments.