4 BL MDS & Myeloproliferative Neoplasms Flashcards Preview

TT DD ex 3 and BL ex 2 > 4 BL MDS & Myeloproliferative Neoplasms > Flashcards

Flashcards in 4 BL MDS & Myeloproliferative Neoplasms Deck (41):
1

2 main features that characterize myelodysplastic syndrome (MDS)

1. ineffective hematopoiesis:
2. increased risk of transformation to AML

2

Ineffective hematopoiesis in MDS

○ The clone (hematopoietic stem cells) is not able to make normal functioning blood cells.

○ Cells often die before leaving the marrow, and usually look abnormal (dysplastic)

3

MDS increased risk of transformation to acute leukemia

hematopoietic stem cell clone slowly acquires enough abnormalities → outright AML

4

2 clinical scenarios of MDS

1. Primary (idiopathic) MDS
2. Secondary / therapy-related (t-MDS)

5

Primary (idiopathic) MDS
- Type of onset?
- Age group:
- Median age of dx:
- Incidence:

○ Insidious onset
○ Usually people >50
○ Median age of dx:70
○ Incidence: 3-5 cases/100,000 persons per year

6

Secondary / therapy-related (t-MDS)
- Type of onset?
- types of therapy leading to MDS

- 2-8 years latency

- use of alkylating agent
- use of topo II
- Exposure of active marrow to ionizing radiation

7

List 3 different types of tests that could be performed to make a diagnosis of MDS.

1) Morphologic evidence of dysplasia in marrow

2) Increased myeloblasts, but less than 20% of blood and marrow cells

3) Presence of a clonal cytogenetic abnormality

8

Morphologic evidence of dysplasia in marrow for MDS

Dyshematopoiesis: > 10% of cell are dysplastic
- Dyserythropoiesis
- Dysgranulopoiesis
- Dysmegakaryopoiesis

9

Dyserythropoiesis

RBC precursors with:
- nuclear budding
- irregularly-shaped nuclei
- lack of coordination between nuclear and cytoplasmic maturation
-increased ring sideroblasts

10

Dysgranulopoiesis

- Nuclear hypolobation of mature neutrophils (<3)
- Neutrophils with bilobed nuclei (pseudo-Pelger-Huet cells)
- Cytoplasmic hypogranularity of neutrophils

11

Dysmegakaryopoiesis

- Megakaryocytes with hypolobated or non-lobated nuclei,
- hyperchromatic nuclei,
- small megakaryocytes

12

4 possible causes of secondary myelodysplasia that might mimic MDS.

1. Certain drugs, including many chemotherapeutic drugs
- use of alkylating agent
- use of topo II
- ionizing radiation

2. Vitamin deficiency (B12, folate, ect)

3. Viral infection

4. Toxin exposure (heavy metals such as arsenic)

13

LOW GRADE MDS:

- Myeloblasts are not increased in frequency (<5%) of marrow

- Refractory Cytopenia with Unilineage Dysplasia (RCUD): good prognosis

- Refractory Cytopenia with Multilineage Dysplasia (RCMD): worse prognosis

14

HIGH GRADE MDS

- Myeloblasts are increased in frequency, (less than 20%)

- Refractory Anemia with Excess Blasts-1 (RAEB-1) : dismal prognosis

- Refractory Anemia with Excess Blasts-2 (RAEB-2): VERY dismal prognosis

15

MDS vs. MPNs:
- source of disease

MDS: marrow is REPLACED by a malignant clone, derived from a transformed stem cell or progenitor cell

MPS: Clonal hematopoietic NEOPLASM arising from a transformed hematopoietic stem cell

16

MDS vs. MPNs:
- onset

Both insidious

17

MDS vs. MPNs:
- hematopoiesis effectiveness

MDS: ineffective
- marrow replaced by malignant clone

MPNs: effective
- marrow fibrosis

18

MDS vs. MPNs:
- ability to develop into acute leukemia

both

19

MDS vs. MPNs:
- age group

MDS:
- usually >50
- median age of dx: 70

MPNs:
- middle-aged to early adults
- rare in children

20

2 reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs

1. spleen sequestering RBCs because they make too many

2. Extramedullary hematopoeisis, causes liver and spleen to enlarge

21

3 possible negative end points for MPNs.

• Without treatment, get:
○ Marrow fibrosis
○ Bone marrow failure
○ Transformation to acute leukemia (less common for MPN than MDS)

22

4 MPNs

1. Chronic Myelogenous Leukemia (CML)
2. Polycythemia Vera (PV)
3. Primary Myelofibrosis (PMF)
4. Essential Thrombocythemia (ET)

23

Chronic Myelogenous Leukemia (CML)
- What is it?
- blood cell count?

CML is an MPN that manifests primarily as a persistent neutrophilic leukocytosis

○ Blood cell counts:
§ Often incidental diagnosis due to abnormal CBC results
§ WBC ranges from 12,000 – 1,000,000 (averages 100,000)


24

Chronic Myelogenous Leukemia (CML)
Phases

• Marrow findings:
1. Initial Chronic phase (stable)
2. Accelerated Phase (Intermediate phase -may or may be bypassed to Blast phase)
3. Blast phase

25

Chronic Myelogenous Leukemia (CML)
marrow findings


1. Initial Chronic phase (stable)
□ Prominent leukocytosis due to a prominent neutrophilia
□ Increased basophils in blood
□ Increased platelets in blood
□ Markedly hypercellular bone marrow with prominent granulocytic hyperplasia

3. Blast phase:
□ Progress to AML -> 20% or more blasts in the marrow or blood

26

Chronic Myelogenous Leukemia (CML)
- cytogenic abnormality

§ BCR-ABL1 fusion gene (must have this for diagnosis)
□ Der(22)t(9:22)→ Philadelphia chromosome

27

Polycythemia Vera (PV) :
- Blood cell counts

Lots of RBCs due to RBCs "really"

- PV usually is diagnosed in a polycythemic phase with:

□ increased blood cell counts
□ Increased neutrophils and platelets in the blood

28

polycythemic phase vs Spent phase (post PV myelofibrosis)

polycythemic phase: increased blood cell counts

Spent: Marrow fibrosis → Fall in blood cell count

29

Polycythemia Vera (PV) :
- marrow findings

1. Trilineage hyperplasia in the marrow
2. Clusters of bizarre large megakaryocytes
3. Spent phase/post-PV myelofibrosis:
□ Extensive marrow fibrosis → marrow failure

30

Polycythemia Vera (PV) :
- cytogenic abnormalities

Activating mutation of JAK2, usually a V617F point mutation.

31

Primary Myelofibrosis (PMF)
- Blood cell counts:

Prefibrotic stage:
□ ↑ Platelets in blood
□ ↑ neutrophils in blood
□ ↑ large megakaryo
(no erythrocytosis)

Progress to fibrotic stage:
□ Falling blood cell count → Leukoerythroblastosis of blood (anemia)

32

Primary Myelofibrosis (PMF)
- Marrow finding

Prefibrotic stage:
□ Granulocytic and megakaryocytic hyperplasia, but no erythrocytosis
□ Bizarre megakaryocytes in marrow

Progress to fibrotic stage:
□ Significant reticulin (collagen) fibrosis of the marrow
□ Bone marrow failure

33

Primary Myelofibrosis (PMF)
- Cytogenic abnormality

§ JAK2 mutations are present in around 50% of PMF cases

§ Cases lacking JAK2 mutations often have mutations of MPL or CALR

34

Essential Thrombocythemia (ET)
what is it? How is it different from PMF?

ET is an MPN characterized by a persistent thrombocytosis.

- Lacks the marrow granulocytic hyperplasia often seen in PMF,
- atypical megakaryocytes in ET are even larger than those in PMF

35

Essential Thrombocythemia (ET)
- blood cell count

§ Persistent thrombocytosis (↑ platelet count)

§ 50% of ET patients are diagnosed based on CBC results while asymptomatic

36

Essential Thrombocythemia (ET)
- Cytogenic abnormality

§ JAK2 mutations are present in around 50% of ET cases

§ Cases lacking JAK2 mutations often have mutations of MPL or CALR

37

most common method of death attributable to disease in polycythemia vera (PV) patients

venous or arterial thrombosis, leading to complications such as DVT, MI, and stroke

38

3 sites where thrombosis should always make one consider the possibility of PV

○ Thrombosis of:

1. mesenteric vein,
2. portal vein
3. splenic vein

should always raise the Possibility of PV.

39

most common treatment for PV.

○ Serial phlebotomy
○ Aspirin therapy (to help prevent clots)
○ If symptoms are problematic, mild chemotherapy can be used, but this increases risk of transformation to acute leukemia

40

peripheral blood smear of a patient with leukoerythroblastosis


Presence of immature granulocytes and immature (nucleated) red cells

41

Peripheral blood smear of pt w/ primary marrow fibrosis (PMF) likely shows?

Leukoerythroblastosis (anemia)