Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Blood and Lymph Unit III > Myelodysplastic Syndrome and Myeloproliferative Neoplasms > Flashcards

Myelodysplastic Syndrome and Myeloproliferative Neoplasms Flashcards

1
Q

Myelodysplastic syndrome (MDS) refers to a group of clonal hematopoietic stem cell disorders characterized by: (2)

A

Ineffective hematopoiesis

Increased risk of transformation to acute myeloid leukemia (AML)

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

What do clones in MDS do?

A

replace the marrow to a varying extent, and result in ineffective production of blood cells in one or more of the myeloid lineages (granulocytic, erythroid, and/or platelet)

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

Two clinical scenarios of MDS:

A

Primary/idiopathic

Secondary/Therapy-related (t-MDS)

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

Primary / idiopathic MDS

A

Usually in person over 50 years old with insidious onset. Median age of dx is 70. Incidence is 3-5/100,000

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

Secondary / Therapy related MDS

A

Occurs as part of a spectrum of t-AML… usually occurs 2-8 years after use of alkylating agents or exposure to fields of active marrow to IR… usually contains whole or partial deletions of chromosome 5/7

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

At what age does primary / idiopathic MDS usually present?

incidence?

A

> 50
median 70

3-5/100,000

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

Secondary / therapy related MDS
occurs how many years post therapy?
usually deletions in which 2 chromosomes?

A

2-8 years post use of alkylating agents

chromosomes 5and/or7

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

When is the diagnosis of MDS usually considered?

A

when there has been at lease one persistent (several months) peripheral cytopenia…

if there is only one cytopenia, it is usually anemia, but rarely persistent isolated neutropenia or persistent isolated thrombocytopenia can be due to MDS.

Persistent cytopenias of two or more lineages in an elderly person is suspicious for MDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

The diagnosis of MDS can be made by evaluating the marrow. Evaluation of the marrow should show (2)

A

morphologic evidence of dysplastic changes in at least 10% of the cells in one or more lineages

clonal cytogenetic findings typical of MDS.

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

Morphologic evidence of dysplastic changes in at least 10% of the cells in one or more lineages (dyshematopoiesis) … These findings can be as follows (3Ds)

A
  1. Dyserythropoeisis
  2. Dysgranulopoiesis
  3. Dysmegakaryopoiesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is it called when you see RBC precursors with nuclear budding, irregularly shaped nuclei, lack of coordination between nuclear and cytoplasmic maturation, and INCREASED RING SIDEROBLASTS?

A

Dyserythropoiesis

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

Dyserythropoesis most characteristic feature?

A

Nuclear irregularities
Prominent ring sideroblasts
Megalablastoid chromatin patterns in RBC precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is it called when you see nuclear hypolobation of mature neutrophils, including neutrophils with bilobed nuclei - called pseudo-Pelger-Huet cells, also cytoplasmic hypogranularity of neutrophils?

A

Dysgranulopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Dysgranulopoiesis most characteristic finding?

A

pseudo Pelger Huet cells (dysplastic neutrophils with two nuclear lobes)
poor cytoplasmic granulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is it called when you see megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryoctyes often of small size?

A

dysmegakaryopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Dyserythropoeisis
Dysgranulopoiesis
Dysmegakaryopoiesis

These are all examples of _____________ which aids in the diagnosis of MDS

A

dyshematopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What clonal cytogenetic findings are typical of MDS (3)

A
  • complex karyotypes with whole or partial deletion of chromosome 5 and or 7
  • note deletion 5q is an isolated cytogenetic finding; seen with a specific type of MDS
  • Trisomy 8; many others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

In the absence of clonal cytogenetic evidence of MDS, care should be taked in establishing a diagnosis of MDS. Potential non-neoplastic causes of secondary myelodysplasia should be excluded first. These include (4)

A
  • Certain drugs (many chemotherapeutic)
  • Deficiencies in B12, folic acid, essential elements
  • Viral infection
  • Toxin exposure, especially heavy metals such as arsenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

MDS can be either low or high grade
What characterizes low grade
What characterizes high grade?

A

LOW: Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral

HIGH: Myeloblasts account for 5%-19% of marrow cells, and/or 2%-19% or more of peripheral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Low grade MDS with dysplasia in only one lineage
Mostly cases of refractory anemia, rarely may be refractory neutropenia or refractory thrombocytopenia
Relatively good prognosis
- >5years
- only 2% to AML by 5 years

A

Refractory Cytopenia with Unilineage Dysplasia (RCUD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Low grade MDS with dysplasia in 2 or more lineages
Worse prognosis than RCUD
- Median survival 2.5 years
- 10 percent of cases transform to AML by 2 years

A

Refractory Cytopenia with multilineage dysplasia (RCMD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q 
High grade MDS
5-9% blasts in marrow, and/or 2-4% blasts in blood
Relatively dismal prognosis 
- median survival of 16 months
- 25% will transform to AML
A

Refractory anemia with excess blasts-1 (RAEB-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q 
High grade MDS
10-19% blasts in marrow, and/or 5-19% blasts in blood 
Very dismal prognosis 
- median survival of 9 months
- 33% will transform to AML
A

Refractory anemia with excess blasts-2 (RAEB-2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

In the setting of a persistent cytopenia, the diagnosis of MDS can be established using one or more modalities (3)

A
  1. morphological evidence
  2. increased myeloblasts but less than 20%
  3. clonal cytogenetic abnormality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When more than 10& of the cells in one lineage appear dysplastic, that qualifies as…

A

dyshematopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

dyshematopoiesis can be subclassified as (3)

A

dyserythropoiesis
dysgranulopoiesis
dysmegakaryopoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Myeloproliferative neoplasms
what are they?
how are they distinct from MDS?

A

Clonal hematopoietic neoplasms arising from a transformed hematopoietic stem cell

The neoplastic clone usually partially or entirely replace the normal marrow cells in multiple lineages

The neoplastic clone usually give rise to increased numbers of normal (NOT DYSPLASTIC) blood cells in one or more lineages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

MPNs -
demographics
incidence

A

usually occur in middle-aged to elderly (Rare in children)

Incidence 6-10/100,000/yr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What characterizes early MPN?

A

Increase in one or more blood cell types with corresponding increase in marrow cellularity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

clinical sign associated with MPN?

A

Splenomegaly and/or hepatomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

MPN onset?

A

usually insidious

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

MPN without treatment progress to?

A

usually

  • excessive marrow fibrosis with resultant bone marrow failure
  • transformation to acute leukemia (much less common for MPNs than for MDS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

MPNs covered in class (4)

A 
Chronic myelogenous leukemia (CML)
Polycythemia Vera (PV)
Primary myelofibrosis (PMF)
Essential Thrombocythemia (ET)
34
Q

Chronic myelogenous leukemia

what is it?

A

CML is an MPN that manifests primarily as a persistent neutrophilic luekocytosis, and is associated with presence of a BCR-ABL1 gene fusion

35
Q

CML

clinical findings?

A

majority of patients present with non-specific signs/symptoms, possible including night sweats, weight loss, splenomegaly, and anemia

significant minority of patients are asymptomatic at diagnosis (often incidental diagnosis due to abnormal CBC)

36
Q

CML
incidence
age?

A

1-2cases/100,000/yr

age 40-60 rare in children / ya

37
Q

CML chronic phase

when are most CMLs diagnosed?

A

The large majority of CML cases are diganosed in the initial phase of the disease, chronic phase

38
Q

Chronic phase CML characterized by?

A

prominent leukocytosis due to a prominent neutrophilia (WBC range 12,000-1,000,000; average 100,000)

Increased basophils

Increased platelets

Markedly hypercellular bone marrow with prominent granlocytic hyperplasia

39
Q

What is the upper limit of normal WBC?

A

11,000

40
Q

If left untreated, CML often progresses to?

A

a blast phase

41
Q

What defines a blast phase progression in CML?

A

20% or more blasts in the marrow or blood (essentially, CML-blast phase is CML that has transformed to acute leukemia)

42
Q

Blast cell type in CML blast phase?

A

In 70% of cases of CML-blast phase, the blasts are myeloblasts
In 30% of cases, the blasts are lymphoblasts

43
Q

CML genetics…
product
process

A

CML is defined by the presence of a BCR-ABL1 gene fusion resulting in a BCR-ABL fusion tyrosine kinase protein

This gene fusion is usually attained through a translocation t(9;22) with the derivative chromosome 22 containing the BCR-ABL fusion gene; this der(22)t(9;22) is called the Philidelphia chromosome

The translocation usually involves a breakpoint in the major breakpoint cluster region of BCR (M-BCR) giving rise to a 210kd fusion protein (p210)

44
Q

difference between Philidelphia chromosome in ALL and CML?

A

In Ph+ALL, the BCR breakpoint is usually in the minor breakpoint cluster region (m-BCR) giving rise to a 190kd fusion protein (p190) -and associated with poor prognosis

45
Q

2 steps to dianose CML?

A

Document the typical blood / marrow findings

Document BCR-ABL1

46
Q

How to find BCR-ABL1? (3 ways)

A

cytogenetics (karyotype)
FISH (fusion probes)
RT-PCR (BCR-ABL mRNA transcripts)

47
Q

CML treatment/prognosis
Untreated median survival?
Former non-targeted survival extension
New PTKI survival?

A

untreated CML survival 2-3yr

former non-targeted extended by a few years

use of small molecular inhibitors, specifically PTKIs has dramatically improved prognosis for CML

  • complete response rate up to 90%
  • 5 year 80-85%
48
Q

Why do we use 2nd and 3rd generation PTKIs for CML?

A

Some CML patients develop resistance to imatinib (Gleevac) through mutations altering the binding site

49
Q

Two reasons for splenomegaly/hepatomegaly in MPNs?

A

sequestration of excess blood cells

extramedullary hematopoiesis

50
Q

Polycythemia vera is an MPN chiefly characterized by?

A

increase in RBC mass (erythrocytosis)

51
Q

in addition to increased RBC mass (erythrocytosis) what else do we usually see in PV

A

Increased neutrophils and platelets in the blood, and trilineage hyperplasia in the marrow

52
Q

PV BM biopsy often shows?

A

trilineage hyperplasia and

cluster of bizarre megakaryocytes

53
Q

Essentially all cases of PV contain an activating mutation…

A

JAK2, usually a V617F point mutation

54
Q

If a patient has a persistent erythrocytosis in the absence of demonstrable JAK2 mutation, consider the possibility of a secondary (reactive) erythrocytosis … secondary erythrocytosis may be seen in? (4)

A

chronic smokers (due to carboxyhemaglobin)

chronic hypoxia

certain hemoglobin disorders

other conditions

55
Q

PV is usually diagnosed in what phase?

A

in the Polycythemia phase, with increased blood cell counts

56
Q

Over time what may PV progress to (phase)

A

spent phase (post pv-myelofibrosis) - characterized by extensive marrow fibrosis with a corresponding fall in blood cell counts

57
Q

Initial presenting symptoms of PV

A 
Headache
dizzy
plethora (dusky/red skin)
pruritis (itching)
paresthesia (pin and needle)
splenomegaly (70%) hepatomegaly (40%)
58
Q

Most serious complication of PV

A

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

59
Q

Thrombosis of the __________ vein, ________vein, or _______ vein should always raise the possiblity of PV

A

mesenteric
splenic
portal

60
Q

Most common PV related C.O.D

A

Thrombotic events

though they more often die of diseases unrelated to PV

61
Q

PV prognosis?

A

relatively good, with median 10-20 yr

62
Q

PV therapy?

A

serial phlebotomy
aspirin therapy

*if symptoms are problematic, mild chemotherapy can be used but increases risk of transformtion to acute leukemia (which is otherwise very low)

63
Q

Primary Myelofibrosis (PMF) is an MPN characterized by?

A

granulocytic and megakaryocytic hyperplasia, but no erythrocytosis

64
Q

___ mutations are present in around 50% PMF (primary meylofibrosis) cases

A

JAK2

65
Q

Primary myelofirbosis - cases lacking JAK2 mutations often have mutations of …. (2)

A

MPL or

CALR

66
Q

Primary myelofibrosis starts in a ______ stage

A

prefribrotic

67
Q

the prefibrotic stage of PMF is characterized by (4)

A
  • hypercellular marrow, with granulocytic and megakaryocytic hyperplasia
  • large, bizarre megakaryocytes in marrow
  • markedly increased platelets in blood
  • usually increased neutrophils in blood
68
Q

Primary myelofibrosis eventually progressive to a fibrotic stage, characterized by: (4)

A

significant reticulin fibrosis of marrow

leukoerythroblastosis of the blood

fall blood cell counts

enlargement of organs (liver, spleen, lymph nodes, other) due to extramedullary hematopoiesis

69
Q

leukoerythroblastosis of the blood =

A

presence of immature granulocytes and immature red cells

70
Q

Primary Myelofibrosis

survival if dx in fibrotic stage?

A

median 5 yr

71
Q

PMF most deaths due to?

A

bone marrow failure

72
Q

PMF minority may transform to?

A

AML

73
Q

Essential Thrombocythemia (ET) is a MPN characterized by?

A

persistent thrombocytosis. It lacks the marrow granulocytic hyperplasia seen in PMF, and the atypical megakaryoctyes in ET are even larger than those in PMF

74
Q

Distinguishing features of Essential thrombocytopenia from primary myelofibrosis?

A

ET lacks marrow granulocytic hyperplasia

atypical megakaryocytes in ET are larger than those in PMF

75
Q

What percent of ET cases have Jak2 mutations?

A

50%

76
Q

Cases of essential thrombocytopenia lacking Jak2 mutations often have mutations of ?

A

MPL or CALR

77
Q

Essential thrombocytopenia

presentation at dx?

A

50% of cases are asymptomatic

signs/symptoms

  • TIA
  • digital ischemia
  • arterial or venous thrombosis (less common than in PV)

Splenomegaly is NOT common

78
Q

Essential thrombocytopenia

survival time?

A

10 years

indolent disease

79
Q

Does ET transform to AML?

A

Rarely

80
Q

What might ET progress to, other than AML?

A

Myelofibrosis

81
Q

What might we see in a blood smear of a patient with leukoerythroblastosis?

A

increased immature granulocytes
immature nucleated red blood cells
increased tear drop shaped RBCs (dacrocytes)

Blood and Lymph Unit III (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions