Myeloid Disorders I

Front 1

Myeloproliferative neoplasms

Back 1

share a common stem cell derived clonal heritage

phenotypic expression depends on which genes have been affected and has led to reclass

Front 2

How are MPN similar

Back 2

may have similar clinical presentations; splenomegaly, increased risk of thrombosis, consitutional symptoms, slow progression

may have similar peripheral blood findings, anemia with variable red cell changes, leukocytosis with immune cells, eosinophils or basophils, platelet abrnomalities

panmyelosis, some fibrosis

Front 3

How do MPN differ

Back 3

predominant cell that is abrnomal

prognosis

cytogenetic findings

treatment

Front 4

Erythrocytosis

Back 4

not all patients with increased red cell number have a malignancy

relative erythrocytosis; normal red cell mass but decreased plasma volume

true erthyrocytosis = increased in red cell mass

primary polycythemia vera and clonal disorder

secondary elevater erythropoetin

Front 5

JAK2

Back 5

mutation in the regulatory domain results in increased JAK2 kinase activity, cytokine independenet growth of cel lines anc cultured bone marrow cells

GAIN of function mutation

present in 95% of patients with polycythemia vera

Front 6

Polycythemia vera

Back 6

increased red cell mass caused by clonal proliferation of erythroid stem cell line

dx; persistantly elevated hemoglobin, presence of JAK2 mutation in 95% of pts, low erythropoetin levels

Front 7

How do p. vera patients present

Back 7

symptoms of hyperviscosity, headaches, blurred vision thrombembolic disease

symptoms of hypermetabolism; gout night sweats pruritus after a hot shower

ofter are asymp

Front 8

Rx for p. vera

Back 8

want to maintain normal hematocrit and platelet count

reason to lower the hemoglobin is to reduce the risk of stroke and other TED

phlebotomy toss out blood

cytotoxic therapy

Front 9

Prognosis for p. verA

Back 9

median survival 15-20 years

thrombosis and hemorrhage major clinical problems

30% develop myelofibrosis - progressive fibrosis in the bone marrow which results in lower hemoglobin and lower platelets reffered to as burnt out p.vera

5% will develop AML

Front 10

Essential thrombocythemia diagnostic criteria

Back 10

sustained platelet increase over 450.000

bone marrow showinf increased nuymber of large mature megakaryocytes but no granulo or erythropoesis

demonstation of Jak2 or MPL515 mutation and if absent NO ecidence for iron deficiency or cause for reactive thrombocytosis

Front 11

What are causes of elevated platelets other than ET

Back 11

any other MPD MDS

reactive cause

familial syndromes

Front 12

ET clinical findings

Back 12

many patients are asymptomatic

splenomegaly 50%

may present with thrombosis or hemorrhage

erythomelagia

rx course; often stable for 10-20 yrs may develop secondary myelofibrosis leukemic transformation 5%

Front 13

ET lab findings

Back 13

platelet count often greater then 1 mil

abnormal large platelets can be seen in the blood film

excess megakaryoctes in the bone marrow

platelet function tests are abnormal especially aggregation abrnomalities

Front 14

Treatment of ET

Back 14

need to risk stratify according to age >60, platelet count and previous thombosis or hemorrhage

modify modifiable risk factors such as smoking, hypertension

aspirin can reduce events

high risk get hydoxyurea with aspirin, OR anegrelide which inhbits megakaryocyte fomrait0on

Front 15

Primary myelofibrosis

Back 15

progressive, generalized fibrosis of bone marrow

fibrosis is caused by hyperplasia of abnormal megas and platelet derived growth factor stimulating the fibroblasts

extramedullary hematopoesis

prognosis is much worse then PV, ET and CML

Jak2 is positive in 50%

Front 16

PMF WHO class

Back 16

presence of mega proliferation and atypia accompanied by collagen or reticulin fibrosis

demonstates Jak 2 postive or MPL515 or in absnesce has no secondary fibrosis

must have 3 major and 2 of 4 minor criteria

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Thrombophilia

Back 17

microcirculatory disturbances

Front 18

PMF clincial features

Back 18

insidious onset

often massive splenomegaly

hepatomegaly

secondary portal hypertension because of splenomegaly

progressive cytopenias

can die of bleeding thrombosis

Front 19

PMF lab features

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leukoerythroblastic blood smear; tear drops nucleated red cells immature WBCs

dry tap bone marrow

Front 20

PMF treatment

Back 20

ruloxitinib

jak 2 inhibitor, it decreases spleen size which often imporves the anemia and thrombocytopenia

decreases cytokine release and the patients have less in the way of systemic symptoms

Front 21

CML

Back 21

first human malignancy in which a non random recurring cytogenetic abrnomaliity identifited

BCR ABL treat with imatinib Gleevac

Front 22

CML findings

Back 22

often slightlt anemic at Dx, gradual rise in WBV with entire spectrum present

marrow is hypercellular, increase M:E ration increased megas some fibrosis

Front 23

Accelerated phase CML

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worsening malaise, fatigue and weight loss

bone pain

blood counts more diffiuclte to control and progressive anemia and thrombocytopenia

progressive splenomegaly

adenopathy

increase in promyelocytes

Front 24

CML treatment

Back 24

bone marrow transplant

TKIs

Imatinib, gleevac targets the specific tyrosine kinase that is overexpressed in the oncogene, can lead to resistance, oral and well tolerated

Front 25

second gen TKIs

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dasatinib = most potent of the TKis

nilotinib 20-30x more ptoent then gleevac bid dosing and multiple drug interactions with both induction and inhibition of cyt p450

Front 26

Cytochrome p450 ind/inh

Back 26

can result in unwanted effects