Malignant Hematology - Myeloid Disorders

Question 1

Which blood cells are considered granulocytes?

Answer 1

Eosinophils
Basophils
Neutrophils

Question 2

What are the myeloproliferative neoplasms?

Answer 2

Polycythemia Vera
Essential Thrombocytosis
Chronic Myelogenous Leukemia (CML)

Question 3

What are the 4 types of myeloid disorders?

Answer 3

(1) Acute Myeloid Leukemia (AML)
(2) Myeloproliferative Neoplasms (MPNs)
(3) Myelodysplastic Syndrome (MDS)
(4) Chronic Myelomonocytic Leukemia (CMML)

Question 4

What are the 3 types of lymphoid disorders?

Answer 4

(1) Acute Lymphocytic Leukemia (ALL)
(2) Lymphoproliferative Disorders (Chronic Lymphoid Leukemia & Lymphoma)
(3) Plasma Cell Dyscrasias (MGUS, MM, primary amyloidosis, Waldenstrom Macroglobulinemia/Lymphoplasmacytic lymphoma)

Question 5

What should you be most worried about if you see Auer rods on a peripheral blood smear?

Answer 5

Acute Myeloid Leukemia

Question 6

How is a diagnosis of AML made?

Answer 6

At least 20% blasts in peripheral blood smear or on bone marrow biopsy.

*Excepts exists, such as in APL, where a PML-RARA mutation is diagnostic of leukemia.

Question 7

What causes the early mortality in acute promyelocytic leukemia?

Answer 7

Due to disseminated intravascular coagulation, resulting in:

(1) Intracranial Hemorrhage
(2) Blood Clots
(3) GI Bleed

Question 8

What is the urgent treatment needed in acute promyelocytic leukemia?

Answer 8

ATRA (all-trans retinoic acid)

Question 9

What is the mutation in acute promyelocytic leukemia?

Answer 9

T(15;17) PML-RARA

Question 10

How do you treat leukostasis in leukemia (4)?

Answer 10

(1) Intravenous fluids
(2) Cytoreduction
(3) TLS prophylaxis
(4) AVOID transfusion

Question 11

What is the management of tumor lysis syndrome?

Answer 11

(1) Correct hyperK and extended lytes
(2) IVF to target high urine output
EITHER:
(A) Allopurinol
(B) Rasburicase (if AKI, uric acid > 535, or no response to allopurinol)

Question 12

What is the target transfusion threshold for thrombocytopenia in acute leukemia who are not bleeding?

Answer 12

Non-APL —> Platelets < 10

APL — Platelets < 30

Question 13

When would you transfuse cryoprecipitate or fibrinogen in acute leukemia?

Answer 13

(A) Non-APL — If bleeding and fibrinogen < 1.5

(B) APL — If fibrinogen < 1.5

Question 14

When would you transfuse FFP in acute leukemia?

Answer 14

If bleeding and PT or PTT > 1.5 ULN

Question 15

How is APL treated?

Answer 15

ATRA + arsenic +/- chemotherapy

Question 16

How is ALL treated (broad terms)?

Answer 16

(1) Induction
(2) Consolidation/Intensification
(3) Maintenance

*High risk of CNS involvement so intrathecal chemotherapy +/- radiotherapy used

Question 17

In which myeloproliferative neoplasms do you get a JAK2 mutation?

Answer 17

(1) Polycythemia Vera (> 95%)
(2) Essential Thrombocytosis (~50%)
(3) Primary Myelofibrosis

Question 18

What is the mutation in chronic myeloid leukemia (CML)?

Answer 18

T(9;22) BCR-ABL tyrosine kinase +

AKA Philadelphia-chromosome +

Question 19

What are the features of chronic phase chronic myeloid leukemia (5)?

Answer 19

(1) Elevated WBCs (mostly neutrophils and precursors)
(2) Splenomegaly
(3) Constitutional Symptoms
(4) Bone marrow + peripheral blasts < 10%
(5) Left shift + basophils + eosinophils in the peripheral blood.

Question 20

What it’s the treatment for chronic myeloid leukemia?

Answer 20

Tyrosine Kinase Inhibitors (Imantinib)

Question 21

What are the phases of chronic myeloid leukemia?

Answer 21

(1) Chronic Phase (< 10% blasts on peripheral smear or bone marrow)
(2) Accelerated Phase (10-19% blasts on peripheral smear or bone marrow)
(3) Blast Phase (>20% blasts on peripheral smear or bone marrrow)

Question 22

What are the features of accelerated phase chronic myeloid leukemia?

Answer 22

(1) 10-19% blasts in the peripheral blood or on bone marrow biopsy.
(2) Worsening counts DESPITE therapy (WBC > 10, platelets > 1000 or < 100)

Question 23

What is the blast phase of chronic myeloid leukemia?

Answer 23

Acute leukemia — typically AML, but 20-30% ALL

At least 20% blasts on peripheral smear or bone marrow biopsy.

Question 24

How do you treat the blast phase of chronic myeloid leukemia?

Answer 24

Treatment as per acute leukemia + tyrosine kinase inhibitor

Question 25

In what malignant hematologist neoplasm would you classically see erythromelagia and aquagenic pruritis?

Answer 25

Polycythemia Vera

Question 26

How should you diagnosis polycythemia vera?

Answer 26

Diagnosis requires 3 major or 2 major and 1 minor criteria: Major: (1) Hb > 165/160 (M/F) or HVT > 49/48 (M/F) (2) BM: Hypercellular for age, trilineage growth (3) JAK2 mutation Minor: Low serum EPO

Question 27

How do you risk stratify patient with polycythemia vera and essential thrombocytosis for thrombosis?

Answer 27

LOW RISK = Age < 60 & no thrombosis hx HIGH RISK = Age > or = 60 OR thrombosis hx High risk get treated with hydroxyurea

Question 28

What do all patients with Polycythemia Vera & Essential Thrombocytosis get treated with?

Answer 28

ASA

Question 29

Why do patients with essential thrombocytosis bleed when their platelets are > 1000?

Answer 29

Acquired VWD

Question 30

What are the diagnostic criteria for essential thrombocytosis?

Answer 30

Diagnosis requires 4 major, or the first 3 major + 1 minor: Major: (1) Sustained platelets > or = 450 (2) BMBx: Hyperlobulated mature megakaryocytes. (3) R/O other WHO diseases (4) JAK, CALR or MPL mutation. Minor No reactive cause

Question 31

What is the JAK-2 inhibitor that can be used in myelofibrosis or polycythemia vera?

Answer 31

Ruxolitinib

Question 32

What are the diagnostic criteria for myelofibrosis?

Answer 32

Requires ALL 3 Major + 1 Minor: Major (All 3): (1) BM: Fibrosis, megakaryocyte proliferation, atypia. (2) JAK 2, CALR, or MPL mutation (3) Rule out other MPN/MDS Minor (1 of): 1. Leukoerythroblastic 2. LDH > ULN 3. Anemia 4. Leukocytosis > 11 5. Palpable splenomegaly

Question 33

What are the peripheral blood smear characteristics of myelofibrosis?

Answer 33

Cytopenias Leukoerythroblastic (nucleated RBCs + left shift) Tear Drop RBCs

Question 34

What are the peripheral blood manifestations of myelodysplastic syndrome?

Answer 34

(1) Hypolobulated/hypogranulated neutrophils (Pelgeroid) (2) Macrocytosis (3) Decreased reticulocytes

Question 35

How is a diagnosis of myelodysplastic syndrome made?

Answer 35

Bone marrow biopsy with aspirate and cytogenetics. Bone marrow features: (1) Hypercellular (usually) +/- ring sideroblasts (2) Dysplasia > 10% (3) Blasts < 20%

Question 36

What is the treatment for patients with MDS?

Answer 36

(A) Low Risk (based on BM workup): Supportive (EPO, transfusions) & lenalidomide (B) High Risk: - Supportive, as above - Azacitadine (prolongs survival) - Cure: Allogenic HSCT

Question 37

What is the differential diagnosis for MDS?

Answer 37

(1) Nutritional Deficiency (Folate/B12/Copper) (2) HIV (3) EtOH (4) Zinc Toxicity (5) Meds - MTX, Azathioprine

Question 38

What are the general criteria for a diagnosis of chronic myelomonocytic leukemia?

Answer 38

(1) Peripheral blood monocytes > 1 & > 10% of total WBCs (2) Blasts < 20% (if > 20 = acute leukemia) (3) Dysplasia in 1 or more myeloid lineage (4) Exclusion of other MPN

Question 39

What is the prognosis of CMML for progression to AML?

Answer 39

15-20% get AML