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Flashcards in Myelodysplasia and MPNs Deck (42)
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1

What's up with RC-UD?

• Refractory Cytopenia with unilineage Dysplasia (RC-UD)
• Cell type that is dyplastic takes the further subdivision
○ Refractory anemia, refractory neutropenia
• Good prognosis (survival rate 5 years from ddx), reglardless of affected lineage

2

What are the 4 main types of MPN that the WHO classifies?

• CML = chronic myelogenous leukemia
• PV = prolycythemia vera
• PMF = primary meylofibrosis
• ET = essential thrombocythemia

3

What are the three common themes for all MPN's?

• MPN - myeloproliferative neoplasm
• Quantitative increase in one or more blood cell types, usually with a corresponding hypercellular marrow
• MPNs often present with splenomegaly or hepatomegaly
• MPNs usually have an insidious onset, often incidentally noticed. Without treatment though there are bad outcomes
• MPNs are usually associated with abnormalities of genes
○ Run the range of big to small (translocations to point mutations)
○ Problems with genes encoding RTKs (receptor tyrosine kinases

4

What are the two general clinical scenarios of MDS?

• Primary/idopathic
○ Older people (mean of ddx is 70 yrs. Old)
○ Age-appropriate cancer
• Secondary/therapy-related (think acquired)
○ Some time of radiation can transform marrow cells
○ The end result is t-AML

5

In what poplulation would you be more suspicious of MPN formation?

• Elderly people (50s - 70s)
• It does happen in children in young adults but much more rare

6

What does MDS stand for and what does that mean?

• MDS = myelodysplastic syndrome (MDS)
• Group of clonal hematopoietic stem cell disorders that have some things in common
○ Ineffective hematopoiesis
○ Increased risk of transformation to actue myeloid leukemia
• There is pancytpenia because of replacement of marrow cells and ineffective production of myeloid cells

7

What is the difference between MDS and MPN?

• MDS is myelodysplastic syndrome, which is a group of conditions all centered on the fact that the bone marrow is failing to make certain blood cell lineages
• MPNs could cause MDS…as MPN is myeloproliferative neoplasms…and the crowding out of the bone marrow by a neoplasm could result in MDS symptoms

8

When do you clinically suspect the diagnosis of MDS?

• When an older patient has 2 or more lines of cytopenia
○ You start wondering if there is a crowding out of those precursor cells in the bone marrow
• One PERSISTENT cytopenia. (not so much anemia, but thrombocytopenia or neutropenia)

9

What are the different chances of transformation to AML in the high grade MDS cases?

• RAEB - 1 = 25% of patients transform to AML
• RAEB-2 = 33% of patients transform to AML

10

How can you confirm your clinical suspicions and diagnose MDS?

• Look at the marrow and see if you can find at least 10% of the cells in one or more lineages with dysplastic changes
○ Term = dyshematapoiesis

11

What does the term dyshematapoiesis mean?

• Look at the marrow and see if you can find at least 10% of the cells in one or more lineages with dysplastic changes

12

What is the median survival rate of RAEB-2?

• RAEB-2 = refractory anemia with excess blasts - 2
• 9 months

13

What are the other, non-neoplastic causes of MDS like situations you should rule out before ddx of MDS by way of neoplasm?

• Drug use (chemotherapy)
• Nutrient deficiency (B12, folic acid, etc.)
• Viral infection
• Toxin exposure (heavy metals like arsenic)

14

What does Low Grade MDS refer to?

• Definition = less than 5% of marrow is Myeloblasts and less than 2% of peripheral blood cells are myeloblasts

15

What does High Grade MDS refer to?

• Definition = more than 5% of bone marrow is myeloblasts and more than 2% of peripheral cells are myeloblasts

16

What is the median survival rate of RAEB-1?

• RAEB-1 = refractory anemia with excess blasts - 1
• 16 months

17

What are the three main types of low Grade MDS?

• Refractory Cytopenia with unilineage Dysplasia (RC-UD)
• Refractory Cytopenia with Multilineage Dysplasia (RC-MD)
• MDS with isolated deletion 5q

18

What are the two different types of High Grade MDS?

• MDS = Myelodysplatic syndrome
• RAEB-1 = refractory anemia with excess blasts - 1
• RAEB-2 = refractory anemia with excess blasts - 2

19

What is special about MDS with isolated deletion at 5q?

• Often associated with:
• Anemia
• increased platelets
• marrow showing distinctive megakaryocytes with small, round, non-lobated nuclei

20

What's up with RC-MD?

• Refractory Cytopenia with Multilineage Dysplasia (RC-MD)
• Defined by low grade MDS with evidence of dysplasia in 2 or more lineages
• Worse prognosis than RC-UD, median survival of 2.5 years
• 10% rate of AML at 2 years

21

What three different, more specific terms can subdivide dyshematapoiesis?

• Dyserythropoiesis
• Dysgranulopoiesis
• Dysmegakaryopoiesis

22

CML is defined by the presence of what cytogenetic finding?

• Translocation, t(9;22)(q34;q11.2) - derivative chromosome is called philedelphia chromosome
• BCR-ABL1 gene fusion
• Constitutive activation of several growth pathways (cross-talk)

23

What drug was the second generation of Gleevac?

• Dasatinib is the second generation BCR-ABL1 inhibitor
• PTKI, designed to hit the major sub-clonal population that is Gleevac resistant

24

One of the main types of MPN by WHO classification is CML. What does that stand for and what is the definition of CML?

• CML = chronic myelogenous leukemia
• Clonal hematapoietic stem cell disorder, associated with the presence of BCR-ABL1 gene fusion t(9;22)
• Prominently manifests as a prominent neutrophilic leukocytosis

25

What are the GENERAL clinical findings of CML?

• Initial signs and symptoms may include fatigue, weight loss, night sweats (B symptoms), splenomegaly, anemia
• Significant minority are asymptomatic and ddx comes from incidental findings on a CBC drawn for a different reason
○ Shows marked leukocytosis (neutrophils)

26

What was the main breakthrough drug for CML treatment and what does it do?

• Gleevac = imatinib
• Inhibits protein tyrosine kinase
• Specifically inhibits the BCR-ABL1 fusion protein
• Cytogenic response rates in 70-90%, good 5 year survival (80%)

27

What are the general epidemiological basics of CML?

• Incidence is 1-2 cases per 100k persons per year (not overly common)
• Typical age of ddx is 40-50 yrs.
The natural course of CML is broken up into two phases.

28

What are the advanced techniques used to confirm the CML diagnosis?

• You need to see the BCR-ABL1 fusion protein
○ Karyotyping (conventional cytogenetics)
○ FISH
○ RT-PCR of fustion protein transcript
• Can get these things from peripheral blood sample

29

What are those phases called?

• CML = chronic myelogenous leukemia
• Chronic phase (often asymptomatic)
○ Would find pretty marked neutrophilia
○ Overall WBC of 12k to 1 million cells (like…a ton)
• Blast phase
○ Think of this as transformation to acute leukemia
○ 20% or more blasts in the marrow or blood

30

What does PV stand for and what is it primarily characterized by?

• Polycythemia vera = PV
• Increase in RBC mass (erythrocytosis), usually accompanied by increased neutrophils and platelets
• Almost invariably contains JAK2 gene mutation (signaling protein).
• Dx is contingent on JAK2 mutation presence