Myelodysplastic Syndromes Flashcards
what are myelodysplatic syndromes
A GROUP OF CLONAL HEMATOPOIETIC STEM CELL DISEASES CHARACTERIZED BY ONE OR MORE PERIPHERAL BLOOD CYTOPENIA(S), WITH DYSPLASIA IN ONE OR MORE MYELOID LINES.
THERE IS AN INCREASED, BUT NOT INEVITABLE, RISK FOR DEVELOPING ACUTE LEUKEMIA.
OLDER ADULTS, MEDIAN AGE 70; MALE PREDOMINANCE
involves cytopenia, cellular bone marrow, and variable maturation
What is classification of MDS based on
Cytopenia(s)
Degree of dysplasia in peripheral blood and bone marrow.
Blast count
what are the IPSS thresholds for cytopenias
Hemoglobin <100x109/L
what are 4 types of MDS
Refractory Anemia (RA)
Refractory Anemia with Ringed Sideroblasts (RARS)
Refractory Anemia with Excess Blasts (RAEB-1)
Refractory Anemia with Excess Blasts (RAEB-2)
what is the main pathophysiology of MDS
abnormal cell clone proliferates
3 heritable conditions associated with increased risk for MDS
Fanconi’s anemia
Schwachman-Diamond syndrome
Diamond-Blackfan syndrome
Clinical findings with MDS
Fatigue and weakness Palor Ecchymoses Hemorrhage Infection
MDS lab finding in erythrocytes
Anemia (Hgb 110 fL) Oval macrocytes Dimorphic anemia in RARS Reticulocytopenia Anisocytosis, poikilocytosis
Basophilic stippling
Howell-Jolly bodies
Nucleated RBC
Membrane abnormalities
MDS lab findings in granulocytes
Leukopenia Neutropenia Left-shift sometimes present Agranular/Hypogranular neutrophils Abnormal granules
Pseudo-Pelgeroid nuclei
Hypersegmentation
Ring nuclei
MDS lab findings in platelets
Thrombocytopenia Thrombocytosis Giant platelets Hypogranular platelets Abnormal granulation Megakaryoblasts
MDS findings in bone marrow
Hypercellular Normocellular Hypocellular <20% myeloblasts Dysplastic features in all cell lines common
Abnormal localization of immature precursors (ALIP)
Ringed sideroblasts
Bone marrow: DYSERYTHROPOIESIS
Megaloblastoid erythropoiesis Giant erythroid precursors Multinucleation Nuclear fragmentation Abnormal nuclear shape Nuclear budding
Karyorrhexis Irregular nuclear or cytoplasmic staining Vacuolization Basophilic stippling Ringed sideroblasts
Bone marrow: DYSGRANULOPOIESIS
Abnormal granulation Hypogranularity Agranularity Abnormal size granules Absent secondary granules
Hyposegmentation
Hypersegmentation
Bone Marrow: DYSMEGAKARYOPOIESIS
Increased megakaryocytes Normal megakaryocytes Decreased megakaryocytes Micromegakaryocytes Hyperchromatic nuclear staining
Nuclear hyposegmentation
Decreased granularity
Giant platelets
Refractory Anemia
PERIPHERAL BLOOD
Anemia
Macrocytosis (MCV <5% of cellularity
Refractory Anemia with Ringed Sideroblasts
PERIPHERAL BLOOD
Anemia
Macrocytosis (MCV 15% (RA has < 15%)
Blasts <5% of cellularity
RAEB-1 (Refractory Anemia with Excessive Blasts-1)
PERIPHERAL BLOOD Cytopenia in two cell lines Normo- or macrocytic anemia Oval macrocytes Reticulocytopenia Dysgranulopoiesis Monocytes 5%)
BONE MARROW
Hypercellular
Dyserythropoiesis
Dysgranulopoiesis
Dysmegakaryopoiesis
Ringed sideroblasts present (auer rods in RAEB-2)
Blasts 5-9% of cellularity (RAEB-2 10-19%)
Prognosis correlates with blast percentage
RAEB-2 (Refractory Anemia with Excessive Blasts-2)
PERIPHERAL BLOOD Cytopenia in two cell lines Normo- or macrocytic anemia Oval macrocytes Reticulocytopenia Dysgranulopoiesis Monocytes 5% of nucleated cells (RAEB-1 <5%)
BONE MARROW Hypercellular Dyserythropoiesis Dysgranulopoiesis Dysmegakaryopoiesis Auer rods may be present (diff than RAEB-1) Blasts 10-19% of cellularity (RAEB-1 blasts 5-9%) Higher risk of leukemia
MDS variants - unclassifiable
Not all cases fit into a subtype (up to 10%)
Trilineage dysplasia with less than 5% blasts in marrow
Survival is poor with worsening dysplasia
Hierarchical approach to classification: AML RAEB - 2 RAEB - 1 RA
MDS variants- therapy related MDS
Occurs following chemotherapy or radiation therapy for another disease.
Related to duration, amount, and courses of therapy.
Often difficult to classify as a specific MDS
Unfavorable prognosis with high risk of leukemia
MDS cytogenetics
Frequently involve chromosomes 5 and 7
Isolated 5q- syndrome is a specific Dx a/w good prognosis
Complex karyotypes (>3 abnormalities) are a/w worse prognosis
MDS prognosis
Median survival worsens with increasing blast percentage and trilineage dysplasia
Median survival (all types) is < 2 years
Leukemic transformation 10-40%
Scoring systems aid in prognosis
MDS therapy
Supportive care RBC transfusion for anemia Platelets for bleeding prophylaxis Antibiotics for infections, neutropenia Growth factors (GM-CSF, EPO) Chemotherapy for poorer prognosis Bone marrow transplantation
Chemotherapy with the hypomethylating agents 5-azacytidine and decitabine has been shown to decrease blood transfusion requirements and to retard the progression of MDS to AML.
Proof of Principle of Tumor Suppressor genes
