MYELODYSPLASTIC SYNDROMES
Babak Tamizi Far MD.Assistant professor of internal medicineAl-zahra university hospital,Isfahan university of medical sciences
Key FeaturesESSENTIALS OF DIAGNOSIS
• Cytopenias with hypercellular bonemarrow
• Morphologic abnormalities in two ormore hematopoietic cell lines
• Cytopenias with hypercellular bonemarrow
• Morphologic abnormalities in two ormore hematopoietic cell lines
Causes
– Idiopathic (most common)– May be seen after cytotoxic chemotherapy
• May evolve into acute myeloid leukemia(AML); had been termed "preleukemia" inthe past
– Idiopathic (most common)– May be seen after cytotoxic chemotherapy
• May evolve into acute myeloid leukemia(AML); had been termed "preleukemia" inthe past
Myelodysplasia encompasses severalheterogeneous syndromes
– Refractory anemia (with or without ringedsideroblasts): no excess bone marrowblasts
– Refractory anemia with excess blasts(RAEB): 5–19% blasts
– Chronic myelomonocytic leukemia (CMML):a proliferative syndrome, includingperipheral blood monocytosis > 1000/mcL
– Refractory anemia (with or without ringedsideroblasts): no excess bone marrowblasts
– Refractory anemia with excess blasts(RAEB): 5–19% blasts
– Chronic myelomonocytic leukemia (CMML):a proliferative syndrome, includingperipheral blood monocytosis > 1000/mcL
GENERAL CONSIDERATIONS
• Group of acquired clonal disorders ofthe hematopoietic stem cell,characterized by cytopenias, usuallyhypercellular marrow, and morphologicand cytogenetic abnormalities
• No specific chromosomal abnormality isseen, but abnormalities inchromosomes 5 and 7 are common
• Group of acquired clonal disorders ofthe hematopoietic stem cell,characterized by cytopenias, usuallyhypercellular marrow, and morphologicand cytogenetic abnormalities
• No specific chromosomal abnormality isseen, but abnormalities inchromosomes 5 and 7 are common
DEMOGRAPHICS
• Occurs most often in patientsaged > 60
Clinical FindingsSYMPTOMS AND SIGNS
• Asymptomatic, with incidentally foundcytopenias
• Fatigue, infection, or bleeding is related to bonemarrow failure
• Wasting, fever, weight loss• Splenomegaly• Pallor• Bleeding• Signs of infection
• Asymptomatic, with incidentally foundcytopenias
• Fatigue, infection, or bleeding is related to bonemarrow failure
• Wasting, fever, weight loss• Splenomegaly• Pallor• Bleeding• Signs of infection
DIFFERENTIAL DIAGNOSIS
• AML ( 20% blasts)• Aplastic anemia• Anemic of chronic disease• Vitamin B12 or folate deficiency
• AML ( 20% blasts)• Aplastic anemia• Anemic of chronic disease• Vitamin B12 or folate deficiency
DiagnosisLABORATORY TESTS
• Anemia may be marked• Mean cell volume is normal or increased• Peripheral blood smear may show macro-ovalocytes• White blood cell count usually normal or reduced;
neutropenia is common• Neutrophils may exhibit morphologic abnormalities,
including deficient numbers of granules, or bilobed nucleus(Pelger-Huet anomaly)
• Myeloid series may be left shifted with small numbers ofpromyelocytes or blasts
• Platelet count is normal or reduced; hypogranular plateletsmay be present
• Anemia may be marked• Mean cell volume is normal or increased• Peripheral blood smear may show macro-ovalocytes• White blood cell count usually normal or reduced;
neutropenia is common• Neutrophils may exhibit morphologic abnormalities,
including deficient numbers of granules, or bilobed nucleus(Pelger-Huet anomaly)
• Myeloid series may be left shifted with small numbers ofpromyelocytes or blasts
• Platelet count is normal or reduced; hypogranular plateletsmay be present
IMAGING STUDIES
• Radiographic findings are variable– Stage I: hilar adenopathy alone– Stage II: hilar adenopathy with parenchymal
involvement– Stage III: parenchymal involvement alone
• Parenchymal involvement usuallymanifests as diffuse reticular infiltrates,but focal infiltrates, acinar shadows,nodules, and rare cavitation are seen
• Pleural effusion occurs in < 10% ofpatients
• Radiographic findings are variable– Stage I: hilar adenopathy alone– Stage II: hilar adenopathy with parenchymal
involvement– Stage III: parenchymal involvement alone
• Parenchymal involvement usuallymanifests as diffuse reticular infiltrates,but focal infiltrates, acinar shadows,nodules, and rare cavitation are seen
• Pleural effusion occurs in < 10% ofpatients
DIAGNOSTIC PROCEDURES
• ECG may show conduction disturbancesand dysrhythmias
• Biopsy demonstrating noncaseatinggranulomas is required for diagnosis
• Easily accessible biopsy sites includelymph nodes, skin lesions, and salivaryglands
• ECG may show conduction disturbancesand dysrhythmias
• Biopsy demonstrating noncaseatinggranulomas is required for diagnosis
• Easily accessible biopsy sites includelymph nodes, skin lesions, and salivaryglands
DIAGNOSTIC PROCEDURES
• Bone marrow aspirate and biopsy arecharacteristically hypercellular, but it maybe hypocellular
• Signs of abnormal erythropoiesis include– Megaloblastic features– Nuclear budding– Multinucleated erythroid precursors
• Bone marrow aspirate and biopsy arecharacteristically hypercellular, but it maybe hypocellular
• Signs of abnormal erythropoiesis include– Megaloblastic features– Nuclear budding– Multinucleated erythroid precursors
DIAGNOSTIC PROCEDURES
• Prussian blue stain may demonstrateringed sideroblasts
• Myeloid series is often left shifted withvariable increases in blasts
• Deficient or abnormal myeloid granulesmay be seen
• A characteristic abnormality is dwarfmegakaryocytes with unilobed nucleus
• Cytogenetics may be abnormal
• Prussian blue stain may demonstrateringed sideroblasts
• Myeloid series is often left shifted withvariable increases in blasts
• Deficient or abnormal myeloid granulesmay be seen
• A characteristic abnormality is dwarfmegakaryocytes with unilobed nucleus
• Cytogenetics may be abnormal
TreatmentMEDICATIONS
• Erythropoietin, 30,000 unitssubcutaneously weekly, reduces redblood cell transfusion requirement in20%
• The combination of high-doseerythropoietin and myeloid growthfactors produces higher response rate,but the cost is very high
• Erythropoietin, 30,000 unitssubcutaneously weekly, reduces redblood cell transfusion requirement in20%
• The combination of high-doseerythropoietin and myeloid growthfactors produces higher response rate,but the cost is very high
MEDICATIONSOral deferasirox (20 mg/kg/d)
• Used as iron chelation therapy• Prevents serious iron overload in
patients who depend on red blood celltransfusion and who do not haveimmediately life-threatening disease
• Used as iron chelation therapy• Prevents serious iron overload in
patients who depend on red blood celltransfusion and who do not haveimmediately life-threatening disease
Lenalidomide– Recommended initial dose is 10 mg orally
daily– Approved for treatment of transfusion-
dependent anemia due to myelodysplasia– Effective in patients with the 5q-cytogenetic
abnormality– Most common side effects are neutropenia
and thrombocytopenia, but venousthrombosis is also seen and warrants aspirinprophylaxis
– Cost is extremely high, and it is not effectiveeither for cell lines other than red blood cellsor for patients with increased blasts
– Recommended initial dose is 10 mg orallydaily
– Approved for treatment of transfusion-dependent anemia due to myelodysplasia
– Effective in patients with the 5q-cytogeneticabnormality
– Most common side effects are neutropeniaand thrombocytopenia, but venousthrombosis is also seen and warrants aspirinprophylaxis
– Cost is extremely high, and it is not effectiveeither for cell lines other than red blood cellsor for patients with increased blasts
MEDICATIONS
• Patients affected primarily with severeneutropenia may benefit from the use ofmyeloid growth factors such as G-CSF
• Azacitidine improves both symptoms andblood counts and prolongs survival and timeto conversion to acute leukemia
• Decitabine can produce similar responses
• Patients affected primarily with severeneutropenia may benefit from the use ofmyeloid growth factors such as G-CSF
• Azacitidine improves both symptoms andblood counts and prolongs survival and timeto conversion to acute leukemia
• Decitabine can produce similar responses
THERAPEUTIC PROCEDURES
• Red blood cell transfusions areindicated for severe anemia
• Allogeneic stem cell transplantation– Only curative therapy for myelodysplasia– Role is limited by advanced age of many
patients and indolent course of disease
• Red blood cell transfusions areindicated for severe anemia
• Allogeneic stem cell transplantation– Only curative therapy for myelodysplasia– Role is limited by advanced age of many
patients and indolent course of disease
OutcomeCOMPLICATIONS
• Infection and bleeding
PROGNOSIS
• Myelodysplasia is ultimately fatal, mostcommonly because of infections or bleeding
• Risk of transformation to AML depends on thepercentage of blasts in bone marrow
• Patients with refractory anemia without excessblasts may survive many years, with low risk ofleukemia (< 10%)
• Patients with excess blasts or CMML have shortsurvivals (usually < 2 years) and higher (20–50%) risk of developing acute leukemia
• Myelodysplasia is ultimately fatal, mostcommonly because of infections or bleeding
• Risk of transformation to AML depends on thepercentage of blasts in bone marrow
• Patients with refractory anemia without excessblasts may survive many years, with low risk ofleukemia (< 10%)
• Patients with excess blasts or CMML have shortsurvivals (usually < 2 years) and higher (20–50%) risk of developing acute leukemia
PROGNOSIS
• Deletions of chromosomes 5 and 7associated with poor prognosis
• Cure rates of allogeneic transplantationare 30–60%, depending on risk statusof disease
• Deletions of chromosomes 5 and 7associated with poor prognosis
• Cure rates of allogeneic transplantationare 30–60%, depending on risk statusof disease
• WHEN TO REFER– All patients should be referred to a
hematologist
• WHEN TO ADMIT– Hospitalization is needed only for specific
complications, such as severe infection
• WHEN TO REFER– All patients should be referred to a
hematologist
• WHEN TO ADMIT– Hospitalization is needed only for specific
complications, such as severe infection