Please enable JavaScript.
Coggle requires JavaScript to display documents.
Myeloproliferative Disorders and Myelodysplasia - Coggle Diagram
Myeloproliferative Disorders and Myelodysplasia
Myeloproliferative Disorders
Polycythemia Rubra Vera
Proliferation of erythroid, myeloid, and megakaryocytic elements within bone marrow
Absolute increase in red cell mass and usually leukocytosis, thrombocytosis, and splenomegaly
Diagnostic Criteria
3 Major or Major #1 and #2 with Minor
Major Criteria
Hb >165 (men) or Hb >160 (women)
Bone marrow with hypercellularity for age
Presence of JAK2 or JAK2 exon 12 mutation
Minor Criteria
Low Serum erythropoietin level
Symptoms
80% Symptomatic
50% c/o headache, pruritus, weakness
30% dyspnea, dizziness, visual changes, weight loss, epigastric pain, painful paresthesias of hands and feet
Clinical Signs
Splenomegaly (50-80%)
Facial plethora (<70%)
Hypertension (<50%)
Hepatomegaly (<50%)
Gout
Cutaneous ulcers
Digital Infarction
Complications
Thrombosis
Bleeding
Occasionally -> AML
Treatment
Phlebotomy
ASA
Myelosuppressive agents like hydroxyurea
Classifications
Primary
Polycythemia vera
Pure erythrocytosis-familial, sporadic
Secondary
Physiologically Appropriate - Decreased tissue oxygenation (High altitude, chronic lung disease, cardiac right sided shunt, carboxyhemoglobinemia)
Physiologically inappropriate - Normal tissue oxygenation (tumors producing erythropoietin, renal, exogenous androgens, exogenous EPO injections)
Relative polycythemia
Essential thrombocytosis
Elevated platelet count in absence of other disease
Problem with clotting or bleeding
Diagnostic criteria
Sustained Platelets >450x10^9/L
Characteristic bone marrow features
Clonal market (JAK2, CALR, MPL)
Exclude other diseases
Peripheral Blood
Bone Marrow
Treatment
Hydroxyurea
Platelet pheresis
Aspirin
Myelofibrosis
Bone Marrow Collagen Fibrosis
Splenomegaly
Peripheral Smear
Tear Drops
Bone Marrow
Dry Taps
Treatment
Supportive care - Red Cell Transfusion
Hydroxyurea to shrink the spleen
Steroids, androgens, epo - improve anemia
Oral JAK-2 inhibitor
Splenectomy
Allogenic Stem cell transplant
Chronic Myeloid Leukemia
Description
CML Cells contian Philadelphia chromosome abnormality (t(9;22))
BCR-ABL-positive
Clinical Features
White Cell Count between 50 and 500 x 10^9/L
Symptoms of hypermetabolism (fever, weight loss, sweats, fatigue, gout)
Massive Splenomegaly
Hypercellular bone marrow
Untreated can progress to terminal acute leukemia
Bone marrow transplant is only known cure
Oral tyrosine kinase inhibitor therapies allow for normal lifespan
CBC
High WBC Count
Low Hemoglobin
High Platelets
Peripheral Blood Smear
Diagnosis
Suspect based on high WBC count
Look for Ph chromosome
Do PCR on blood for BCR/ABL Transcript
Treatment
Gleevec: Tyrosine Kinase Inhibitor
Inhibits activity of ABL tyrosine kinase
Effect agent in Chronic phase CML
Taken orally daily for rest of life
Results in disappearance of Ph chromosome
Mechanism of Action
2nd Generation and 3rd Generation tyrosine Kinase
(Dasatinib, Nilotinib, Bosutinib, Ponatinib)
Bone Marrow Transplant rarely required for CML
Disorders characterized by abnormal proliferation (increased number of normal effective hematopoietic cells)
JAK2V617F Mutation in MPDs
Present in all 3 phenotypically related conditions
Somatic mutation in hematopoetic progenitors
Can Activate JAK-STAT signaling when co-expressed with the erythropoietin receptor
Myelodysplastic Disorders
Disorders that share basic features (marrow dysplasia + Cytopenias)
Pathogenesis
Inflammation
Genetic Instability
Epigenetic Changes
Niche Disruption
Clinical Features
Bone Marrow Failure in Elderly
Complications of any or all cytopenias: Anemia, infection, bleeding
Morphologic Characteristics
Anisocytosis and Macrocytosis
Pseudo-Pelger-Huet Cells
Oval macrocytes, aniso/poikilocytosis, giant platelets
Peripheral blasts
Macrocytic Anemia
Pseudo Pelger-Huet Cell
Chromosomal Abnormalities
Cytogenic abnormalities very common
Most common are chromosomal deletions (5-, 5q-, 7q-, 7-, 20q-, Y-, trisomy 8)
Diagnostic Criteria
Cytopenias
Evidence of Clonality
Exclude other causes of cytopenia
Prognosis
Depends on:
Age
Number of Cytopenias
Percentage blasts
Cytogenic abnormalities
Treatment
Low/Int-1 Risk Disease
Directed to specific symptoms
Symptomatic Anemia
Hgb <100, requiring transfusion
Erythropoitin stimulating agents
Symptomatic neutropneia
ANC <1.0
Ulcers or Recurrent/Severe/Opportunistic Infections
G-CSF (growth Factor)
Symptomatic Thrombocytopenia
Bleeding
Tranexamic acid and/or platelet transfusion
Int-2/High Risk Disease
Supportive Transfusion/Tranexamic Acid/Antibiotics
Hypmethylating agents
Conventional Chemotherapy
Allogenic Stem Cell Transplant
