1/10 Myeloproliferative Disorders - David Flashcards

1
Q

chronic myeloproliferative disorders

A
  • chronic myelogenous leukemia (BCR/Abl positive)
  • chronic neutrophilic leukemia
  • chronic eosinophilic leukemia
  • polycythemia vera
  • chronic idiopathic myelofibrosis
  • essential thrombocythemia
  • chronic myeloproliferative disease, unclassifiable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

chronic myelogenous leukemia (CML)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

phases of CML

A
  1. 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
  1. blast phase (blast crisis)
  • 20% or more blasts
  • extramedullary blast prolif
  • large foci or clusters of blasts on bm biopsy
  1. chronic phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

CML: genetic abnormality

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

CML drug

resistance

new drugs

A

imatinib

bcr-abl tyrosine kinase inhibitor: blocks ATP binding pocket

“Gleevec”

more recently, T315I mutation → nilotinib, dasatinib, bosutinib, ponatinib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

essential thrombocytosis

how to differentiate between clonal thrombocytosis and secondary/reactive thrombocytosis

mangement recommendation

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

polycythemia rubra vera

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

dysregulated JAK signaling

pathways

A

JAK2 mutation common in:

  • PV 65-97%
  • ET 32-57
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

myelofibrosis

myeloid metaplasia

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

systemic mastocytosis

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

myelodysplastic syndrome

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

hypomethylating agents

A

mech: reverse silencing of tumor suppressor genes induced by cytosine methylation
ex. 5-azacytidine, decitabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly