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Flashcards in Myelodysplasia and MPNs Deck (42)
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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


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


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


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


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


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


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


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)


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


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


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


What is the median survival rate of RAEB-2?

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


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)


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


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


What is the median survival rate of RAEB-1?

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


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


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


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


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


What three different, more specific terms can subdivide dyshematapoiesis?

• Dyserythropoiesis
• Dysgranulopoiesis
• Dysmegakaryopoiesis


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)


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


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


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)


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%)


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.


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

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


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


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