Myelodysplastic Syndromes (MDS)

BASICS

Heterogeneous clonal stem cell disorders with dysplastic marrow cells and peripheral blood cytopenias (anemia, thrombocytopenia, neutropenia)
Dysplasia = abnormal marrow cell development/differentiation
MDS shares features with AML but has <20% blasts (MDS is premalignant, risk for AML transformation)

Mutations in hematopoietic stem cells, leading to clonal expansion, cytopenias, marrow replacement
80% idiopathic
Environmental: benzenes, chemo/radiation (iatrogenic MDS, up to 10 yrs later)
Classifications: WHO, ICC (cytogenetics, dysplasia, blasts)
Genetics:
>90% cytogenetic anomalies (translocations, aneuploidy)
5q deletion: most common; isolated 5q has better prognosis, chemo-related has worse
Other: -7, +8, -Y

Age >60
Tobacco, benzene, pesticides, petroleum
Prior chemo/radiation
Inherited syndromes (Fanconi, Shwachman-Diamond, severe congenital neutropenia, familial platelet disorder)
Autoimmune (vasculitis, CTD, inflammatory arthritis)
ESRD on dialysis

Symptoms depend on cytopenias: fatigue (most common, often disproportionate), recurrent infections, bleeding, weight loss, exertional dyspnea
Fevers, night sweats, weight loss uncommon
Assess for toxin exposure

CBC + smear, flow cytometry, chemistry, HIV/hep panels, EPO, B12/folate
Bone marrow biopsy: blast % (<20% MDS, ≥20% AML), karyotyping, FISH, mutation studies
Cytogenetics: 30–80% have clonal abnormalities; remainder have microdeletions or point mutations

Macrocytic anemia, basophilic stippling, hyposegmented neutrophils (pseudo Pelger-Huet), thrombocytopenia
Low retic index (hypoproliferative marrow)

Treatment depends on cytopenias, classification, risk, comorbidities, patient preference
IPSS-M/IPSS-R: for risk/prognosis
Lower-risk MDS: symptom-based
Asymptomatic: monitor only
Symptomatic: treat anemia (Hb<10), thrombocytopenia (plt<20k or <50k with bleeding), neutropenia (ANC<500 or <1000 + infections)

Anemia:
Blood transfusion
Erythropoiesis-stimulating agents (ESA): 30–60% response, for Hb<10 and EPO<500 (SE: HTN, thrombosis)
Monitor for iron overload (chronic transfusion)
Lenalidomide: for isolated 5q, decreases transfusion need
Luspatercept: for 2+ PRBC/8wks in low/intermediate risk
Thrombocytopenia/neutropenia:
TPO receptor agonists (romiplostim, eltrombopag, close monitor for leukemic transformation)
G-CSF/antibiotics for neutropenia
Low-intensity chemotherapy:
Hypomethylating agents (HMA): azacitidine, decitabine (if unresponsive to supportive therapy)
High-intensity chemotherapy + SCT:
Allogenic SCT is only curative, reserved for high-risk and fit patients