WBC Disorders Cases

Question 1

In order to make a diagnosis of acute leukemia, how many blasts (at a minimum) would you have to see on PB (or BM) smear?

Answer 1

20%

Question 2

What types of infections cause neutrophilia?

Answer 2

Bacterial – like streptococcal tonsillitis

Question 3

What kind of cell type is likely to be increased in the PB with whooping cough?

Answer 3

Lymphocytes

Bordetella Pertussis causes a leukemoid reaction that results in a lymphocytosis

Question 4

What is the significances of “toxic change” in the peripheral blood neutrophils?

Answer 4

Indicates the presence of primary granules

–usually associated with an inflammatory process (sepsis)

Question 5

CML

Answer 5

Middle aged (40-60)
Extreme neutrophilia
Fatigue, wt loss, splenomegaly, LAD
Labs: WBC = 10K-500K, basophilia, myeloblasts < 10%, decreased LAP

Question 6

CML what does the BM look like?

Answer 6

Hypercellular with effective hematopoiesis

Question 7

What is a common (95%) cytogenetic abnormality in CML?

Answer 7

t(9;22) BCR-ABL fusion geen
Philidelphia chromosome
Not specific to CML

Question 8

What is the defect associated with BCR-ABL fusion gene?

Answer 8

A constitutively active tyrosine kinase

Question 9

What are the three phases of CML?

Answer 9

Chronic phase (median survival 3-5 years)
Accelerated phase (12-24 months)
Blast phase (3-6 months)

Question 10

What is the treatment for CML?

Answer 10

Imatinib

Question 11

What is Imatinib fails?

Answer 11

SCT

Or new oral tyrosine kinase inhibitors: Dasatinib, Nilotinib, Bosutinib, Ponatinib

Question 12

If a patient stops taking CML meds what will likely happen?

Answer 12

The patient will likely progress to acute leukemia

Question 13

Which myeloproliferative neoplasm has a JAK2 mutation in nearly ALL cases?

Answer 13

Polycythemia Vera

Question 14

What are some clinical findings of PV?

Answer 14

HSM
Ruddy faces
H/a
Budd-Chiari syndrome
Gout

Question 15

Is EPO decreased or increased in PV? Why?

Answer 15

EPO is decreased with sustained increased in HCT/Hb
Normal SaO2

Marrow is doing it’s own thing producing a lot of RBC’s independent of EPO production

Question 16

Patient presents with weakness, bleeding from nose and mouth
Petechiae and ecchymoses
WBC: 50,000/uL
Increased D-dimer, PT and PTT 
Consistent with DIC

Answer 16

Most likely Acute Myeloid Leukemia

Specifically Acute Promyelocytic Leukemia

Question 17

What cytogenetic abnormality is commonly assoc with APL?

Answer 17

t(15;17)

Produces PML-RARa fusion product

Question 18

What functional defect is associated with product of PML-RARa fusion gene?

Answer 18

A block in terminal differentiation due to retinoic acid receptor disruption
RA is important for myeloid maturation – arrest at promyelocyte stage

Question 19

What is the common therapy for PML?

Answer 19

ATRA (all-trans retinoid acid)

Question 20

Which cytogenetic abnormality has a similar prognostic significance to t(15;17) in a patient with AML?

Answer 20

t(8;21)*** answer
inv(16)
t(15;17)

All have favorable prognoses
11q23 has an intermed/unfavorable prognosis

Question 21

76 yo female with weakness and pancytopenia
Hypercellular BM with frequent hypogranular and hypolobated neutrophils
Small, hypolobated megakaryocytes

Answer 21

Myelodysplastic Syndrome

Question 22

What is the most important diagnostic criterion for differentiating a myelodysplastic syndrome from an acute myeloid leukemia with myelodysplasia-associated changes?

Answer 22

The bone marrow blast percentage

>20% = AML 
<20% = MDS

Question 23

What are some chromosomal abnormalities associated with MDS?

Answer 23

Monosomy 5 or del5q
+8
Monosomy 7 or del7q

In 50% of patients

Question 24

What is the therapy for MDS?

Answer 24

Supportive care + growth factors
SCT

Hypomethylating agents
Lenalidomide
Histone Deacetylase Inhibitors

Question 25

What is the name of the hypomethylating agent we should know? What is their mechanism of action?

Answer 25

Decitabine HYPER methylation blocks gene transcription and allows cell to divide (silences genes) HYPO methylation blocks DNMT and prevents methyl group binding and allows gene expression

Question 26

What are blasts in MDS likely to be positive for on flow cytometry?

Answer 26

CD34, CD117, CD13, CD33

Question 27

``` 50 yo male with fatigue Hb: 9 MCV: 100 Plt: 30,000 WBC: 80,000 Blasts: 60,000 Normal fibrinogen ``` Blood smear shows Auer bodies Flow cytometry: CD13, CD33, CD34, CD117, MPO + HLAl-DR +

Answer 27

AML

Question 28

Common clinical presentation of acute leukemias

Answer 28

HSM, PAINLESS LAD, skin involvement, testicular involvement, bone pain THROMBOCYTOPENIA ALL (children <20) AML (adults 30-60)

Question 29

What are some good prognostic cytogenetic classifications of AML?

Answer 29

t(8;21) inv(16) t(15;17) Or with FAB type M3

Question 30

What are some BAD prognostic cytogenetic classifications of AML?

Answer 30

Any patient with adverse karyotypic abnormalities (-5,-7, del(5q), abn(3q), complex or resistant disease

Question 31

What is the therapy for AML?

Answer 31

Induction: 7 + 3 with Ara-C + Daunorubicin Consolidation: HIDAC or Ara-C

Question 32

``` 60 yo male Fatigue and night sweats Hemoglobin 11 gm/dl Exam: spleen palpable 4cm at MCL Labs: otherwise unremarkable Teardrop cells ```

Answer 32

Primary myelofibrosis (PMF)

Question 33

What common mutation is associated with PMF?

Answer 33

JAK2 mutation (in about 50%)

Question 34

What is a possible treatment being explored for PMF?

Answer 34

JAK2 inhibitors