Heme/lymph - Dr. Jones - Myeloprolif & Related Disorders

Front 1

leukocytosis

Back 1

inc in # of blood leukocytes --> common rxn to inflamm. states

could indicate neoplastic growths

Front 2

factors influencing leukocyte count

Back 2

- rate of release from storage

- proportion adherent to BV walls

- rate of extravasation

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causes of leukocytosis (cells lines as well)

Back 3

*basophilia - myeloprolif ds; rare

*lymphocytosis - viral

monocytosis - chronic infxn

neutrophils - pyogenic bacT infxn

eosinophilia: allergic/parasitic

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ex of leukocytosis

Back 4

- flooding peripheral blood by neoplastic WBCs (leukemia)

- acute viral infxn

- leukemoid reaction

Front 5

neutropenia

Back 5

red in # of granulocytes (<15,000/uL); vulnerable to bacT, viral & fungal infxn

Front 6

neutropenia:
pathogenesis

Back 6

1. red. or ineffective prod of neutrophils (dec prod)

2. acc. removal of neutrophils (inc excretion)

Front 7

ex of dec. prod (neutropenia)

Back 7

- suppression of myeloid stem cells

- suppression of committed granylocytic precursors (drug exposure)

- ds state due to ineffective granulopoiesis

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ex of inc excretion (neutropenia)

Back 8

- immune mediated injury to neutrophils

- splenic sequestration

- inc peripheral use

Front 9

BM changes w/ neutropenia:

1. dec production

2. inc excretion

Back 9

1. hypOcellular BM

2. hypERcellular BM

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myeloid neoplasms

Back 10

neoplasm that arises from progenitor cells that nLly give rise to terminal differentiated cells of myeloid seris

Front 11

AMLs

Back 11

immature progenitor cells accumulate in BM

Front 12

myelodysplastic syndromes

Back 12

a/w ineffective hematopoiesis & resultant peripheral blood cytopenias

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chronic myeloproliferative disorders

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inc prod of >=1 terminally differentiated myeloid elements leading to elevated peripheral blood counts

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both __ & __ can often transform into ____ myelogenous leukemias

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myelodysplastic syndromes
chronic myeloproliferative disoders
acute

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CML transformation into ____ can occur

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acute lymphoblastic leukemia/lymphoma

Front 16

AMLs affect primarily what age group?

b/w what ages?

Back 16

adults

b/w ages of 15-39 yoa

Front 17

accumulation of proliferating neoplastic myeloid precursor cells in marrow causes what?

Back 17

suppression of remaining nL hematopoietic progenitor cells

Front 18

AML: classification

# of categories?
subgroups?

Back 18

8 --> M0-M7

M0-3: degree of maturation
M4-7: lineage of leukemic blasts

Front 19

AML: classification

2 important ones? chromosomal loc?

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M2 - maturation t(8;21)

M3 - hypergranular, DIC, t(15,17); see HIGH # of BASOPHILS leading to thrombotic/bleeding crises

Front 20

AML: dx

based on?

often confused w/?

morphological giveaway

Back 20

1. >20% of myeloid blasts in marrow

2. ALL

3. Auer rods

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What are Auer rods?

Back 21

abnL azurophilic granules (M2,3) found in myeloblasts NOT in monoblasts (peroxidase -)

Front 22

AML: clinical characteristics

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1. similar to ALL
2. symp similar to anemia, neutropenia and thrymbocytopenia: fatigue, fever & spont. mucosal & cutaneous bleeding
3. bleeding due to thrombocytopenia
4. lympadenopathy/splenomeg
5. infiltration of skin gingiva
6. nests of hematopoietic areas

Front 23

AML: prognosis

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1. 60% get complete remission w/ chemo
2. 15-30% remian free from ds for 5 yrs
3. t(8;21) or inv(16) -> good prognosis

Front 24

AML: prognosis

when in the prognosis poor?

Back 24

Philadelphia chromosome translocation (9;22)
&
prior hx of myelodysplastic ds

**Philadelphia CreaML cheese (CML)

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MDS: general

Back 25

1. group of clonal stem cell disorders w/ ineffective hematopoiesis
--> inc risk of transformation to AML

2. BM replaced w/ abnL offspring of rpoliferating pluripotent stem cell

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MDS: development

2 types

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1. idiopathic or 1* MDS occur around 50 yoa and > insiduously

2. t-MDS - complication of previous drug or radiation therampy 2-8 yrs ltr

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MDS: morphology

Back 27

DR. M. N. Heut Pawn
1. dysplastic differentation of myeloid lineage
2. ringed sideroblasts
3. megaloblastoid maturation
4. nuclear budding abnL
5. psuedo-pelger-Huet cells
6. pawn ball megakaryocytes
7. myeloblasts <20% overall BM

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DR. M N Heut Pawn

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1. dysplastic diff myeloid lineage
2. ringed sideroblasts
3. megablastoid maturation
4. nuclear budding abnL
5. Pseudo-Pelger Heut cells
6. Pawn ball megakaryocytes

Front 29

MDS:

ringed sideroblasts

Back 29

erythroblasts w/ iron-laden mitochondria visible

Front 30

MDS:

megaloblastoid maturation

Back 30

resembling that seen in vitB12 & folate def.

Front 31

MDS:

nuclear budding abnL

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nuclei w/ misshapen, polypoid outlines

Front 32

MDS:

Pseudo-Pelger-Huet cells

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neutrophils w/ 2 nuclear lobes in marrow & peripheral blood & giant platelets

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MDS:

pawn ball megakaryocytes

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megakaryocytes w/ single nuclear lobes or multi separate nuclei

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MDS: clinical course

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1. progression to AML 10-40%
2. survival:
-> 1* MDS 9-29 mos
-> t-MDS 4-8 mos

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chronic myeloproliferative disorders (MPDs): general

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1. neoplastic cells in multipotent progenitor cell -> gives rise to mature myeloid lineages

2. MATURE CELLS!

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chronic myeloproliferative disorders (MPDs): general

4 MC

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1. CML
2. polycythemia vera
3. essential thrombocytosis
4. 1* myelofibrosis

Front 37

CML:
etiology

Back 37

1. 25-60 yoa can be effected
2. peak incidence 40s-50s

Front 38

CML: pathophys

Back 38

1. *specific translocation at Philadelphia chromosome (Philly CreaML cheese) t(9;22)
-> 9 = BCR gene
-> 22 = ABL gene
2. BCR=ABL fusion gene -> **automatic accelerated cell division (unregulated myeloprolif)

Front 39

CML: pathophys

why to maturity?

Back 39

automatic accelerated cell division - ras & tyrosine kinase activity --> cells to MATURATION

- peripheral blood leukocytosis >100,000 cells/mm3

Front 40

CML: morphology

Back 40

1. hypercellular BM
2. inc reticulin fibers
3. peripheral blood: keuko >100,000 - PMNs, metamyelocytes, myelocytes
4. splenomegaly

Front 41

CML: clinical features

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1. insidious onset w/
2. mild-mod anemia and
3. hypermetabolism from inc cell turnover
4. median survival 3 yrs

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CML: clinical features pt 2

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5. after 3 yrs -> accelerated phase
6. w/in 12 mos - accelerated phase -> acute leukemic (**BLAST CRISIS**)

Front 43

CML: clinical features

what is accelerated phase

effects on eating habits?

Back 43

increasing anemia & thrombocytopenia and peripheral blood basophilia

eat alot; bad b/c inc cell turnover

Front 44

CML: tx

Back 44

1. BM transplant
2. inhibition of BCR-ABL kinase

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polycythemia vera: general

Back 45

1. neoplastic process in multipotent myeloid stem cells
2. *** inc prod of erythroid & granulocytic cell lines

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polycythemia vera: cause

Back 46

unknown; ***progenitor cells have dec requirement for EPO

Front 47

polycythemia vera: morphology

Back 47

1. hypercellular BM: inc erythroid cells, granulocytes, platelets
2. inc marrow reticulin
3. peripheral blood smear: thrombocytosis, inc basophils and giant platelets

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polycythemia vera: labs

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1. inc HCT, inc red cell mass
2. dec serum EPO

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polycythemia vera: clinical course

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1. insidiously in late mid ages (60s)
2. symps due to inc red cell mass and HCT
3. inc risk of bleeding & thrombotic episodes
4. anbL blood flow - cyanosis, stagnation & deoxy blood
5. h/a, dizzy, pruritis

Front 50

polycythemia vera: clinical course pt 2

Back 50

6. hyperurecemia
7. peptic ulcerations

Front 51

polycythemia vera: tx

Back 51

maintain HCT @ nL levels by phlebotomies