3.26 NIELL Myeloproliferative Diseases Flashcards
Myeloid Neoplasms Def and Types
Def: arise from hematopoietic progenitors and typically give rise to clonal proliferations that replace BM
AML: Blast accumulation >20-30% in BM and Replace Normal Elements
Myeloid Proliferative disorders: see terminal diff. but exhibits increase or dysregulated growth.
-Usually see increase in formed elements in peripheral blood
Chronic Myelogenous Leukemia
- Usually Presents 45-55 age
- 9:22 Philadelphia Chromo: present in 100% of RBC, WBC, Monocytes and platelets
- -See cont activation of Tyrosine Kinase
- PB: WBC precursors present
- Basophilia is common
- Elevated Uric Acid: Excess purine breakdonw
- Increased B12 b/c increased Transcobalamine 1
Phases of CML
Chronic Phase (5-6yrs)
Accelerated Phase (6-9 months)
-Anemia, thrombocytopenia and increased blast cells
Blast Crisis (3-6 months)
-20% or more blasts in the marrow (decreased diff)
Older Treatments for CML
Busulfan
Hydroxyurea: maintains WBC in chronic phase but does not decrease % of BCR-ABL cells
Interferon: Replaced by Imatinib
BM transplant (not available with all pts)
Targeted Therapies
Imatinib: takes up ATP binding site
-!st line therapy (1st gen) May see Neutropenia and Thrombocytopenia
-Good response in Chronic Phase, some response in blast phase
Dasatinib and Nilotinib (2nd Gen)
-Both faster remission than Imatinib (less info known)
-higher affinity for BCR-ABL, Kinase and can be useful in imatinab resistance
JAK-2 Mutations
-MPD-associated mutation in JAK-2
V617F-JAK2 is a common mutation seen
-PV, ET and MF
Idiopathic Myelofibrosis (PMF) -Causes
Occurs around 65
Causes:
-Myeloproliferation with granulocytic hyperplasia and megakaryocytosis
-Marrow fibrosis with increased collagen Type I, III, IV, and V in marrow (mostly III)
-Fibrosis closely coorelates with increased dysmorphic megakaryocytes in the marrow
-Fibrosis is the result of release of cytokines from the abnormal megakaryocytes
Clinical and Physical findings of PMF
Fatigue, weakness, shortness of breath, bone pain
Physical Findings:
-Hepatomegally (75%) Splenomegally (100%)
-Muscle wasting, pheripheral edema, purpura, bone tenderness
PMF labs
-Early: Thrombocytosis
-Bizarre changes in megs (peripheral and BM)
-Aniso and poikliocytosis
-TEAR DROPS
–Happen anytime there is a problem with BM architecture
-Nucleated RBCs and WBCs
BASOPHILIA
Marrow: increased fibrosis and abnormal megs
Other Important Symptoms of PMF
Portal Hypertension: resulting in ascites, esophageal and gastric varices
Osteosclerosis: prox femur & humerus pelvis, vertebral bodies, ribs and skull
Treatment of PMF
- Not very good at treating, give transfusions
- Lenalidamide may achieve remission
- Radiation used to manage symptoms
- BM transplant is curative but most pts are too old (high mortality rate)
- Roxolitinib: Jak2 inhibitor, some results but not great
Causes of Secondary Thrombocytosis
- Acute and transient: trauma, Major surgery and acute bleeding
- More sustained thrombocytosis: inro def, chronic infection, chronic inflamm disease, neoplasia
- Lifelong thrombocytosis: splenectomy or asplenic pts
Characteristics of Secondary Thrombocytosis
- Generally, no splenomegally
- no extreme plt elevations
- morphology and func is normal
- Thrombosis and bleeding is rare
- Usually see elevated levels of thrombopoetin that coorelates with the plt count
Essential Thrombocytosis
Least common of MPDs
Diagnosed age 50-60
ET Clinical Features
Splenomegally in 40% of pts
- Aortic and mitral valvular leaflet thickening or vegetations
- Leukemic transformation is less than othe other MPDs
- Serum Thrombopoetin levels are normal or elevated and does not coorelate with the platelet count**
Risks of ET
-Some pts with only bleeding or thrombosis
–risk for thrombosis: previous, older age and ass CV risk factors (smoking)
Bleeding is >1,500,000 plts, b/c plts are not func normally
-Arterial Thrombosis is more common than venous
Treatment of ET
Hydroxyurea: brings down plt #
-Anagrelide: interferes with terminal differentiation of megas and also decreases # of ptls
Polycythemia
Increase in total # of RBC or decrease in plasma volume making the blood more viscous
-Appropriate if in response to Hypoxia, inappropriate if not hypoxic
Secondary Polycythemia
- Can be due to increase in alititude, is a response to hypoxic state
- Increase in Epo leading to increased synthesis of RBC
- Can also be caused by localized hypoxia of the kidney
Polycythemia Rubra Vera (PRV)
Myeloproliferative disease involving stem cells that are neoplastic w/ loss of all control of proliferation, nothing will inhibit
Common in 50-60yr olds
-Pruritus (itching) is a major symptom
-Thrombosis is a major concern, usually put on low dose aspirin to try and help
4H’s of PRV (Goljan)
-Hyperviscosity: increase in peripheral resistance b/c of increase viscosity leads to sluggish circulation
–main cause of thrombosis (biggest problem)
–Why phlebotomies are done
-Hypervolemia: increase in plasma volume that matches increase in RBC syn
-Histonemia: All cells are increased (RBCs, WBC, Plts, Mast and basophils)
–Itching***:cause by increase in mast cells
-Hyperuriacemia: b/c hematopoietic cells are increased and when they die purine is breakdown and uric acid is increased
RBC mass: up, plasma volume: up, Oxygen saturation is Normal, Epo: low
Spent Phase of PRV
Eventually may develop:
- Anemia, Leucocyosis, marrow fibrosis, enlarging spleen
- Mimics Myeloidfibrosis at this stage
