Lecture 13 in hematology by Dr.Alaa Fadhil Alwan
Myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders
characterized by one or more peripheral blood cytopenias and dysplasia of at least one
lineage (classically three lineages) in the bone marrow. The approximate incidence is
two to four cases for a population of 100,000 annually.
ETIOLOGY
Etiology is poorly understood. MDS occurs infrequently before the age of 50 but its
incidence increases rapidly thereafter. Prior exposure to chemotherapeutic agents,
ionizing radiation, or benzene are risk factors .
PATHOPHYSIOLOGY
The vast majority of MDS cases are acquired. The development of MDS is due to
accumulated DNA damage in the hematopoietic stem cell. This damage may take the
form of chromosomal gains or losses, translocations, or point mutations..
CLINICAL AND LABORATORY MANIFESTATIONS
Patients commonly present with symptoms of fatigue and decreased exercise
tolerance due to anemia. Less often, patients will have bleeding, easy bruisability, or
recurrent bacterial infections as an initial complaint.
Physical examination may reveal pallor, peripheral edema, and if the anemia is
severe, evidence of heart failure. Petechiae may be present on the lower extremities or
the buccal mucosa if severe thrombocytopenia is present (i.e., the platelet count is less
than 20,000/L); ecchymoses may be observed. Splenomegaly may be present,
especially in patients with chronic myelomonocytic leukemia (CMML). Laboratory
tests may reveal an isolated decrease of one peripheral blood count or multiple
cytopenias. The anemia may be microcytic, normocytic, or macrocytic. An.
Thrombocytopenia may be present, although the platelet count may be elevated in
patients with refractory anemia (RA) and an isolated 5q- abnormality, or in some
cases of RARS. The peripheral blood smear often demonstrates cellular
morphological abnormalites. The neutrophils may be hypogranular, and the nucleus
may have a bilobed appearance (pseudo-Pelger-Huet abnormality).. Chemistry tests
typically are normal except the lactate dehydrogenase, which is elevated as a result of
increased rate of cell death in the bone marrow.
The bone marrow biopsy usually is hypercellular for the age of the patient. However,
approx 15% of patients have a hypocellular marrow (cellularity <25%). The hallmark
of MDS is the presence of tri-lineage dysplasia in the marrow. The erythroid series
usually is megaloblastic in appearance, with prominent nuclear-cytoplasmic
asynchrony. The erythroid cells may have additional abnormalities including bi-
nuclearity or nuclear budding. Ringed sideroblasts, erythroid precursors with iron-
laden mitochondria surrounding the nucleus, may be increased and they exceed 15%
of the nucleated bone marrow cells in patients with RARS. Megakaryocytes
frequently are small (micromegakaryocytes) with decreased nuclear ploidy (mono- or
binucleated). The myeloid series usually is left-shifted and increased myeloblasts are
present in more advance stages.
Classification of Myelodysplastic Syndromes:
A. FAB Classification of Myelodysplastic Syndromes
Subtype Blood myeloblasts BM myeloblasts Other features
RA <1% <5%
RA with RS <1% <5% RS > 15% BM cells
RAEB <5% 5–20%
CMML < 5% < 20% AMC > 1000/mL
B. WHO Classification of Myelodysplastic Syndromes
Myelodysplastic Syndromes
RA with or without RS Erythroid-only dysplasia (<5% blasts)
Refractory cytopenia with multi- Two or three lineage dysplasia (<5% blasts)
lineage dysplasia
RAEB-1 Blasts 5–9%
RAEB-2 Blasts 10–19%
5q- syndrome <5% blasts
Myelodysplastic syndromes, Dysplasia, not meeting above criteria
unclassifiable
Myelodysplastic/myeloproliferative syndromes
CMML
Atypical chronic myelogenous leukemia
JMML
TREATMENT
supportive care is the treatment of choice for many patients. Blood transfusions
frequently are required for symptomatic anemia and antibiotics are administered for
bacterial infections. Chronic red blood cell transfusions lead to iron overload. In
patients who will require ongoing transfusional support, iron chelation should be
considered after 20 U of packed red cells have been administered or when the serum
ferritin level exceeds 1000 ng/mL. Platelet transfusions typically are reserved for
individuals who are actively bleeding or those who have experienced life-threatening
bleeding below a certain platelet count. Hematopoietic growth factors may benefit a
minority of patients with MDS. Allogeneic stem cell transplantation (SCT) is the only
curative modality for MDS,