268. MDS

Question 1

MDS

• definition
• pathogenesis
• epi
• RFs
• CM

Answer 1

MDS: group of clonal hematopoietic stem cell neoplasms characterized by: (1) peripheral cytopenia (ineffective bone marrow hematopoiesis), (2) morphologic DYSPLASIA (abnormal cells in myeloid lineage), (3) higher risk of transformation to AML (10-40%)

PGen: genetic changes in single stem cell disrupt maturation and confer growth advantage, as well as increased degree of apoptosis of bone marrow precursors = cytopenia, worsens over time

Epi: Older (>70) males

RF: de novo has unknown etiology (maybe ⌬ and tobacco)

• therapy related (t-MDS): due to chemo or radiation tx (WORST PROGNOSIS)
• inherited Fanconi anemia, dyskeratosis congenita
• acquired aplastic anemia

CF:
Anemia: fatigue, SoB, Chest pain, palpitations, dizziness, syncope
Neutropenia: recurrent/severe infection
Thrombocytopenia: petechiae, bruising, bleeding
Infrequent Organomegaly
SLOW ONSET AND LONG STANDING

Question 2

MDS

• Dx
• Bone Marrow
• Genes
• Classification

Answer 2

DX: Hx of sx, CBC of pancytopenia with low reticulocytes
Bone Marrow: hypercellular, erythroid hyperplasia and dysplasia (multiple nuclei/nuclear budding), dysplastic megakaryocytes (small, hypolobulated nuclei, separated nuclear lobes), dysplastic granulocytes (hyposegmented, hypogranular - Pseudo Pelger-Huet Cells)
Genes: CH Abnormalities: -7 or del(7q), del(5q), +8
Make sure to rule out non-neoplastic causes of cytopenia and dysplasia (vitamin deficiency, meds, chemo)

WHO

1. MDS with single lineage dysplasia (<5% blasts BM)
2. MDS with multilineage dysplasia (<5% blasts BM)
3. MDS with ring sideroblasts (<5% blasts BM)
4. MDS with isolated del(5q) (<5% blasts BM)
5. MDS with EXCESS BLASTS
   - MDS-ED-1 (blasts 5-9% BM or 2-4% PB)
   - MDS-ED-2 (blasts 10-19% BM or 5-19% PB)

Blasts > 20% is AML

Question 3

MDS

• Prognostic Factors
• Tx

Answer 3

VARIABLE PROGNOSIS
De novo: 9-29mo
Therapy-related MDS: 4-8mo (DISMAL)

Risk groups
Low: MDS with single lineage dysplasia or ring sideroblast
Intermediate: MDS with multilineage dysplasia or excess blasts-1 (5-9%)
High Risk: MDS-EB-2 (10-19%)

Most important prognostic factors

1. Blast Count (%)
2. Cytogenetics
   - future: gene mutations

Tx: nothing if asx

sx: supportive (transfusion, ABx)
- low intensity: immunosuppression
- high intensity: HSC tx (only cure, but most pts too old or unfit)
- del(5q) = LENALIDOMIDE