1/10 Myeloproliferative Disorders - David Flashcards
chronic myeloproliferative disorders
- chronic myelogenous leukemia (BCR/Abl positive)
- chronic neutrophilic leukemia
- chronic eosinophilic leukemia
- polycythemia vera
- chronic idiopathic myelofibrosis
- essential thrombocythemia
- chronic myeloproliferative disease, unclassifiable
chronic myelogenous leukemia (CML)
clonal nyeloproliferative malignant neoplasm of pluripotent hematopoietic stem cell
- multiphase disease
- chronic phase: see all diff stages of devpt on smear
- blast phase: don’t see whole range of devpt, see mostly immature
- in both: basophils
- overproduction of granulocytic and often megakaryocytic lineage
- M=F, 50 years, usually sporatic
fatigue, malaise, weight loss, early satiety (bc spleen enlarged, compressing stomach), bleeding, chloromata
can be asymptomatic
phases of CML
- accelerated phase
- 10-19% blasts
- periph basophils at least 20%
- persistent thrombocytopenia or persisten tthrombocytosis
- enlarging spleen
- cytogenetic evidence of clonal changes
- megakaryocytic prolif in sheets/clusters
- blast phase (blast crisis)
- 20% or more blasts
- extramedullary blast prolif
- large foci or clusters of blasts on bm biopsy
- chronic phase
CML: genetic abnormality
Philadelphia chromosome: t(9;22)
- 95% of pt with CML
- BCR/Abl tyrosine kinase
leads to defects:
- reduced stem cell adhesion to marrow stroma
- failure of apoptosis
- discordant nuclear/cytoplasmic maturation
CML drug
resistance
new drugs
imatinib
bcr-abl tyrosine kinase inhibitor: blocks ATP binding pocket
“Gleevec”
more recently, T315I mutation → nilotinib, dasatinib, bosutinib, ponatinib
essential thrombocytosis
how to differentiate between clonal thrombocytosis and secondary/reactive thrombocytosis
mangement recommendation
presence of sustained platelet count over 450k/uL without any other identifiable cause
(i. e. dx of exclusion:)
* pt may be asymptomatic, may present with thrombosis, may present with bleeding diathesis if platelets dysfx
unique features of clonal vs secondary thrombocytosis
- no underlying systemic disease
- digital/cerebrovascular ischemia
- 40% splenomegaly
- giant platelets on smear
- maybe abnormal platelet fx
- incr megakaryocytes
recommendations:
- hi risk: low dose aspirin + hydroxyurea
- int/lo risk: low dose aspirin
- all pt: manage reversible CV risk factors aggressively
polycythemia rubra vera
clonal disorder: overproduction of RBCs
- maybe also granulocytes (50%), platelets (50%)
- splenomegaly (75%)
may present with dyspnea due to high whole blood viscosity, neuro impairment due to hypersicosity, thrombosis, splenomegaly
erythromelalgia (burning pain in digits)
pruritus after warm water exp
factors to consider in diagnosis:
- JAK2 mutation positive
- serum epo measurement low
management
- venesection to maintain hematocrit
- low dose aspirin
- manage reversible thrombotic risk factors aggressively
- cytoreduction if required (interferon below 40, hydroxyurea above 40)
dysregulated JAK signaling
pathways
JAK2 mutation common in:
- PV 65-97%
- ET 32-57
myelofibrosis
myeloid metaplasia
uncommon condition: marrow cavity becomes fibrosed → inhosp environment for hematopoiesis
- anemia, thrombocytopenia, sometimes leukopenia
- in response, hematopoietic progenitors leave marrow, circulate in blood, and start extramedullary hematopoiesis in LIVER and SPLEEN
- splenomegally, hepatomegaly → abd discomfort
- if splenectomy, liver failure may occur due to massive infiltration by hematopoietic cells
typical presentation: cytopenias w/ splenomegaly
classic presentation: DACROCYTE (teardrop cell)
systemic mastocytosis
multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organs
- often mutation in 816 codon of cKit
sx related to release of: histamine, leukotrienes, TNF, prostaglandins
- anaphylaxis
- skin issues
- osteoporosis/lytic lesions
- GI: diarrhea, ulcers
- hematologic: anemia, splenomegaly
tx
- trigger avoidance
- antihistamines
- antileukotrienes
- Tyr kinase inhibitors
myelodysplastic syndrome
spectrum of clonal meyloid disorders
- ineffective erythropoiesis (hypercellular marrow bc not working right)
- peripheral cytopenias
- qualitative disorders of blood cells/precursors
- variable predilection to undergo clonal evo → florid acute myeloid leukemia
assoc with chromosomal abnormalities, esp 5 and 7
assoc with prev alkylating agent tx in some patients
subtype: 5q- syndrome (loss of long arm of chr5)
hypomethylating agents
mech: reverse silencing of tumor suppressor genes induced by cytosine methylation
ex. 5-azacytidine, decitabine
