Heme disorders/leukemia

Question 1

Answer 1

Neutropenia:
ANC <1.5 × 109/L in adults
ANC <1.0 × 109/L= increased risk of infections
ANC < 0.5 × 109/L = severe neutropenia
Mechanism
Increased rate of removal/destruction of neutrophils
Decreased production
Ineffective hematopoiesis
Changes in ratio of circulating versus marginal pool of neutrophils

Question 2

neutropenia

etiology

Answer 2

Inherited or acquired
Alloimmune neonatal neutropenia
Autoimmune neutropenia in children
Secondary autoimmune neutropenia
SLE
Felty syndrome (RA)
Cyclic neutropenia
Drugs
Antiretrovirals
Cephalosporins
Phenytoin
Sulfonamides
Chemotherapeutic agents
Viral infections
Chronic idiopathic neutropenia (CIN)

Question 3

Neutropenia

Monitoring/Treatment

Answer 3

Determine etiology
May require bone marrow biopsy and aspiration
Monitor for and treat infections quickly
ANC <500 with fever requires aggressive antibiotic care (and hospitalization)
Stop offending medications

Question 4

Myelophthisic Anemias

general
peripheral smear

Answer 4

Bone marrow infiltration by fibrosis, malignancy, or infection
Idiopathic
Primary myelofibrosis
Reactive
Malignancy
Infection

Peripheral smear
Leukoerythroblastic reaction
Tear drop cells
Circulating nucleated red blood cells
Early white blood cells

Question 5

Primary myelofibrosis

general

Answer 5

Alternate names: chronic idiopathic myelofibrosis, angiogenic myelofibrosis, and myelofibrosis with myeloid metaplasia

Initially hypercellular bone marrow and then becomes hypocellular

Extramedullary hematopoiesis in liver, spleen and lymph nodes

Associated with JAK2 (65%), CALR, and MPL mutations
May be primary or secondary
Age ≥ 50 yr
Median survival 5 years
May convert to AML
Significant splenomegaly

Question 6

Myelofibrosis

Laboratory evaluation
Peripheral smear

Answer 6

Anemia

Peripheral smear
Giant abnormal platelets
Teardrop poikilocytosis (aka: dacrocyte)

Bone marrow biopsy and aspirate
May be unable to obtain bone marrow aspirate (Dry tap)
Send for genetic mutations

Question 7

Myelofibrosis

treatment

Answer 7

Supportive treatment
Transfusions
Will need indefinite treatment

• Jakafi (Ruxolitinib) PO Jak2 inhibitor
  Helpful despite JAK2 status
  Reduce splenomegaly and symptoms
• Hydrea (Hydroxyurea)
  May decrease splenomegaly by 50%
• Radiation
  Painful bone marrow sites
  Splenomegaly
• High risk disease or inadequate response
  Allogenic stem cell transplant

Question 8

Reactive Myelofibrosis

Malignancy related and infection related

Answer 8

Acute leukemias
Chronic leukemias/myeloproliferative neoplasms (MPN)
Myelodysplastic syndromes (MDS)
Multiple myeloma
Metastatic cancer
Breast cancer
Lung cancer
Prostate cancer

Fungal
Miliary tuberculosis
Viral
EBV
CMV
HIV
Hepatitis

Question 9

Myelodysplastic Syndrome (MDS)

General
General blood and bone marrow examination

Answer 9

A bone marrow failure disorder characterized by hypercellular marrow. There are low peripheral blood counts due to ineffective cell formation with limited survival
Can be a primary or secondary disease
Ranges in severity
Asymptomatic disease with mild normocytic/macrocytic anemia
Transfusion-dependent anemia with conversion to an acute leukemia

Seen in peripheral blood and bone marrow
Peripheral cytopenias
Hypercellular marrow
Morphologic dysplasia
Genetic abnormalities

Question 10

MDS

labs

Answer 10

Normocytic/macrocytic anemia
Neutropenia
Left shift (more immature cells/ banding)
Blasts may be present
< 20%

Question 11

MDS

Abnormal Cellular Function

Answer 11

Granulocytes
Decreased adhesion
Deficient phagocytosis
Decreased chemotaxis

Erythrocytes
Shortened survival
Decreased response to EPO

Platelets
Increased bleeding despite platelet number

Question 12

MDS

Tx

Answer 12

Improve quality of life and prolong survival!
Supportive care
Transfusions
Iron chelation (Deferasirox/ExJade)
Hematopoietic stem cell transplantation
Limited due to advanced age of patients

• Lenalidomide (Revlimid)
  5q deletion
  Transfusion dependent
• Azacitidine (Vidaza), decitabine (Dacogen)
  High risk MDS
• Growth factors
  Low EPO level
  Epogen (Procrit)
  Severe neutropenia
  G-CSF (Neupogen)

Question 13

Revlimid (Lenalidomide)

MOA

Answer 13

Vascular Endothelial Growth Factor (VEGF) Inhibitor
Inhibits angiogenesis by reducing levels of VEGF, TNF-a, and IL-6
Inhibits cell proliferation and induces apoptosis of tumor cells
Used with Dexamethasone

Question 14

Revlimid (Lenalidomide)

adverse effects

Answer 14

Side effects:
Neutropenia
Thrombocytopenia
Venous thrombosis
ASA 325mg daily prophylaxis

REMS program
Human teratogen

Question 15

Vidaza (Azacitidine)

MOA

Answer 15

MOA: Antimetabolite
Inhibits DNA hypomethylation
Dosing: 75mg/m2 days 1-7 every 28 days for up to 6 cycles
Used with Dexamethasone
Improve overall survival
Delay conversion to AML

Question 16

Vidaza (Azacitidine)

adverse effects

Answer 16

Side effects
Pancytopenia
Renal failure
Interstitial lung disease
Rash

Question 18

Hereditary spherocytosis

general

Answer 18

Defect in the membrane-cytoskeleton structure resulting in spherocytes in the peripheral blood (abnormally susceptible to lysis)
Heterogeneous alterations in 1 of 5 genes that encodes proteins that maintain the integrity of the RBC membrane.

Autosomal dominant
Rare
Most common RBC membrane disorder
More common in northern Europeans- 1:2000-1:5000

May occur at any age and severity level

Question 19

Hereditary spherocytosis

Lab differences
HS trait/mild HS/ Moderate HS/ Severe HS

Answer 19

Question 20

Hereditary spherocytosis

S/Sx

Answer 20

Anemia sx (fatigue, pallor, weakness, SOB)
extravascular hemolysis: jaundice, hemoglobinurea, splenomegaly, pigmentex gallstones with or without RUQ abdominal pain.

Question 21

Hereditary Spherocytosis

Dx

Answer 21

Family history
Osmotic fragility testing +
CBC, MCHC ≥ 36 g/dL
Peripheral smear
Spherocytes

Question 22

HS

Tx

Answer 22

No good treatment
Splenectomy in severe cases
Pneumococcus, Haemophilus influenzae type B, and mengococcus vaccination required before surgery
Cholecystectomy for symptomatic gallstones

Question 23

Answer 23