Myelodisplastic and Myeloproliferative Disease

Question 1

WhaList 2 main features that characterize myelodisplastic syndrome (MDS)

Answer 1

1. ) Ineffective hematopoesis - not able to make normal blood cells. Die before leaving bone marrow.
2. ) Increased risk of transformation to acute leukemia - often seen as precursor to AML

Question 2

What are primary and secondary MDS?

Answer 2

Primary (idiopathic) MDS - idk whats causing it. Median age of diagnosis - 70.

Secondary MDS (therapy related, t-MDS) - part of spectrum of therapy related AML. 2-8 yrs after treatment w/ alkylating agents/topoisomerase II inhibitors. Whole or patial deletions of Chr. 5 and/or 7

Question 3

What 3 tests that can be done to diagnose MDS?

Answer 3

1. ) Morphologic evidence of dysplasia (more than 10% of cells in one lineage appear dysplastic, called dyshemapoeisis.)
2. ) Increased myeloblasts, but less than 20% of blood and marrow cells
3. ) Presence of clonal cytogenetic abnormality (complex karyotype Chr. 5+/- 7, trisomy 8, isolated deletions of 5q)

Question 4

List 4 possible causes of secondary myelodisplasia that LOOKS like MDS but isnt

Answer 4

1. ) Vitamin Deficiency (B12, folate)
2. ) Toxin Exposure (heavy metals)
3. )Exposure to certain drugs
4. )Viral infections

Question 5

Compare/contrast high grade and low grade MDS

Answer 5

Low grade MDS - myeloblasts not increased above normal, 5% in marrow, >2% in blood.

Question 6

What are the three subtypes of low grade MDS?

Answer 6

Refractory cytopenia with unilineage dysplasia - relatively good prognosis. Median survival >5 yrs, rt of transformation to AML 2% over 2 yrs.

Refractory cytopenia with multilineage dysplasia- dysplasia in 2 or more lineages. Median survival 2.5 yrs, rt of transformation to AML 10% for 2 yrs

MDS w/ isolated deletion 5q - associated q/ anemia, increased platelets, marrow w/ megakaryocytes w small, round, non-lobated nuclei

Question 7

What are the two subtypes of high grade MDS?

Answer 7

Regractory Anemia with Excess Blasts-1 - 5-9% blasts in marrow, 2-4% blasts in blood. Medial survival 16 months, 25% transform to AML

Regractory Anemia with Excess Blasts-2 - 10-19% blasts in marrow, 5-19% blasts in blood. Median survival 9 months, 33% transform to AML.

Question 8

What are myeloproliferative neoplasms (MPNs?)

Answer 8

Clonal hematopoietic stem cell disorders due to proliferation of one or more myeloid lineages.

Neoplasmic clone usually partially or entirely replaces normal marrow cells.

Usually gives rise to more NORMAL cells.

Diseases of adults in their 50-70s mostly. 6-10 per 100K ppl per yr.

Question 9

List 2 reasons for frequent occurence of splenomegaly and hepatomegaly in patients with MPNs.

Answer 9

1. ) Sequestration of blood cells b/c you’re making hella
2. ) When marrow becomes fibrotic, you have extramedullary hematopoeisis, your spleen and liver try to make blood so get all big

Question 10

What are the four MPNs (that we covered?)

Answer 10

1. Chronic Myelogenous Leukemia
2. Polycythemia Vera
3. Primary Myelofibrosis
4. Essentail Thrombocythemia

Question 11

Wtf is CML?

Answer 11

Defined by presence of BCR-ABL1 gene fusion
t(9;22)(q34;q11.2)

Persistent neutrophilic leukocytosis. Increaed white counts, non-specific symptoms.

Typical age of diagnosis 40-60

Question 12

What are the two phases of CML?

Answer 12

1. ) Chronic phase - prominent leukocytosis, fairly stable disease. Avg white count = 100,000. Increased basophils, platelets, hypercellular bone marrow w/ glanulocytic hyperplasia. Megakaryocytes are small and round!!!
2. ) Blast phase - occurs if you don’t treat CML in chronic phase. 20% or more blasts (basically acute leukemia.) 70% of the time, blasts are myeloblasts, however 30% of cases transform into ALL.

CML may progress directly from chronic phase to blast phase, or go through an intermediate accelerated phase.

Question 13

How is CML treated?

Answer 13

Small molecular inhibitors for tyrosine kinase! Imatinib (Gleevac)

Question 14

What is polycythemia vera?

Answer 14

Increase in RBC mass, increased neutrophils and platelets, tri-lineage hyperplasia in the marrow.

All cases of PV have an activating mutation of JAK2 (usually V617F point mutation.)

Question 15

What are potential illnesses that may appear like PV (with excess RBC production?)

Answer 15

Called secondary erythrocytosis.

1. ) Smokers (due to carboxyhemoglobin)
2. )Chronic hypoxia (like livin’ in Colorado!)
3. ) Heme disorders

Question 16

Name some initial symptoms of PV

Answer 16

Headaches, dizziness, plethora, pruitus (itching), parasthesias (pins and needles sensations) and enlarged spleen or liver.

Question 17

What are patients with PV at an increased risk for?

Answer 17

Clotting, venous or arterial thrombosis, DVT, MI, stroke

Question 18

What are the two phases of PV?

Answer 18

1. Polycythemic phase(butt ton of cells)

2. Spent phase (marrow fibrotic, blood count falls)

Question 19

What is essential thombocythemia (ET?)

Answer 19

MPN characterized by persistent thrombocytosis. Large, atypical megakaryocytes.

JAK2 muts present in about 50% of the cases.

Question 20

What are the three most common causes of death in PV pts?

Answer 20

Thrombosis in the mesenteric vein, portail vein and splenic vein

Question 21

What is the most common treatment for PV?

Answer 21

blood letting!!!! (serial phlebotomy) Sometimes aspirin therapy. With a lot of symptoms, low grade chemo, but MAY cause increased risk of progressing to acute leukemia a

Question 22

What does the bone marrow look in individuals w/ patients with marrow fibrosis

Answer 22

Large amount of pink, cartilaginous material - normal blood cells seen within the fibrotic materials but aren’t able to get out. Very low cellularity.