T6 - MYELODYSPLASTIC SYNDROMES (MDS)

Summary
Myelodysplastic syndromes (MDS) are a group of hematological cancers in which
malfunctioning pluripotent stem cells lead to hypercellularity and dysplasia of the bone marrow.
This, in turn, leads to cytopenia of one or more cell lines (thrombocytopenia, erythrocytopenia,
leukocytopenia). Most cases of MDS have a primary, idiopathic etiology, while a minority of
cases are secondary to an underlying cause. MDS usually affects elderly patients and has a
slowly progressive course. Clinical features vary depending on the type of MDS and the affected
cell lines, and may include signs of anemia (e.g., fatigue, weakness, pallor), recurrent infections,
and/or petechial bleeding. Diagnosis of MDS requires blood tests, bone marrow biopsy, and
possibly genetic analysis. While mild cases may be closely monitored, severe disease typically
requires blood transfusions supplemented with erythropoietin, vitamins, and, in some cases,
granulocyte colony-stimulating factor. Medical therapy (e.g., chemotherapy or
immunosuppressants) may also help to manage the disease, but allogenous stem cell
transplantation is the only curative treatment. In 30% of cases, the disease progresses to acute
myeloid leukemia.
→ ver vídeo Osmosis

Etiology (ver vídeos Amboss)

● Primary MDS (90% of cases)
○ Tends to occur in elderly patients
○ Unknown etiology: likely due to spontaneous mutations
● Secondary MDS (10% of cases): caused by exogenous bone marrow damage
○ Treatment-related MDS: following cytostatic therapy (alkylating agents,
topoisomerase II inhibitors, azathioprine, etc.)
○ Benzene and other organic solvents
○ Radiation damage: therapeutic radiation, radioiodine therapy, ionizing
radiation
○ Paroxysmal nocturnal hemoglobinuria
Clinical features
● Asymptomatic in 20% of cases
● Depending on the affected cell line:
○ Erythrocytopenia (70% of cases) → symptoms of anemia
○ Leukocytopenia with increased susceptibility to bacterial infections, especially
of the skin
○ Thrombocytopenia with impaired primary hemostasis → petechial bleeding
● Hepatosplenomegaly (uncommon)

Complications
● Depending on the chromosomal aberrations detected in pluripotent stem cells, up to
30% of MDS cases may progress to acute myelogenous leukemia. The diagnostic criterion
for AML is ≥ 20% blast cells in the bone marrow.

Diagnosis
● CBC with peripheral smear
○ Normocytic or macrocytic anemia (rarely microcytic) of refractory type
(refractory anemia) - Anemia is often the first sign of illness and does not respond to the usual
therapy (folic acid, vitamin B12, iron), hence it is called refractory anemia.

○ Other possible findings

■ Leukocytopenia and/or thrombocytopenia
■ Nucleated RBCs, Howell-Jolly bodies, basophilic stippling
■ Pseudo-Pelger-Huet anomaly
■ Neutrophils with hyposegmented nuclei (usually bilobed)
■ Seen in peripheral blood smears of patients undergoing
chemotherapy
■ Large, agranular platelets, and megakaryocytes (in MDS with
myelofibrosis)
● Bone marrow biopsy: hypercellular, dysplastic bone marrow with numerous cells of all
three cell lines with blasts, megakaryocytes, etc.
○ The amount of dysplastic cells depends on the type (see “Classification”
above).
○ Ringed sideroblasts
● Chromosome analysis: In > 50% of patients, chromosomal aberrations (primarily located on
chromosomes 5, 7, and 8) can be detected at the time of diagnosis.
Classification
● The WHO classification distinguishes between six types of myelodysplastic
syndromes, based on the number of dysplastic cell lines and the percentage of blasts
in the bone marrow, among other criteria:
○ MDS with multilineage dysplasia (MDS-MLD; most common)
○ MDS with single lineage dysplasia (MDS-SLD)
○ MDS with ring sideroblasts (MDS-RS), with two subtypes:
■ MDS-RS with single lineage dysplasia (MDS-RS-SLD)
■ MDS-RS with multilineage dysplasia (MDS-RS-MLD)
○ MDS with excess blasts (MDS-EB), with two subtypes:
■ MDS-EB1
■ MDS-EB2
○ MDS with isolated del(5q) (rare)
○ MDS, unclassifiable (MDS-U; very rare)
● WHO also has a clinical classification
○ Primary MDS: no identifiable cause
○ Secondary MDS: cause is known

Treatment
The therapeutic approach depends on a patient's presentation, age, and comorbidities. More
aggressive therapy (e.g., chemotherapy, stem cell transplantation) is generally reserved for
younger, healthier patients.

● Mild cytopenia: "watch and wait"

● Severe cytopenia
○ Supportive treatment
■ Mainstay of treatment: RBC and platelet transfusions depending on
cell counts
■ To compensate for the high cell turnover: vitamin supplementation
(vitamin B6, B12, folate)
■ In cases of symptomatic anemia and low erythropoietin (EPO) levels:
synthetic EPO
■ In cases of neutropenia: granulocyte colony-stimulating factor
■ If infection occurs: antibiotics
○ Medical therapy
■ Chemotherapy: if myeloblasts are elevated and since the disease
may progress to acute myeloid leukemia (AML) However, the treatment is
not curative, since its effect on slowly dividing dysplastic cells is limited.

■ Immunosuppressive agents
■ Lenalidomide: the drug of choice for patients with 5q deletion
○ Allogenous stem cell transplant is the only curative option: indicated for
patients < 55 years of age with late-stage MDS