WBC Disorders Cases Flashcards
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?
20%
What types of infections cause neutrophilia?
Bacterial – like streptococcal tonsillitis
What kind of cell type is likely to be increased in the PB with whooping cough?
Lymphocytes
Bordetella Pertussis causes a leukemoid reaction that results in a lymphocytosis
What is the significances of “toxic change” in the peripheral blood neutrophils?
Indicates the presence of primary granules
–usually associated with an inflammatory process (sepsis)
CML
Middle aged (40-60)
Extreme neutrophilia
Fatigue, wt loss, splenomegaly, LAD
Labs: WBC = 10K-500K, basophilia, myeloblasts < 10%, decreased LAP
CML what does the BM look like?
Hypercellular with effective hematopoiesis
What is a common (95%) cytogenetic abnormality in CML?
t(9;22) BCR-ABL fusion geen
Philidelphia chromosome
Not specific to CML
What is the defect associated with BCR-ABL fusion gene?
A constitutively active tyrosine kinase
What are the three phases of CML?
Chronic phase (median survival 3-5 years) Accelerated phase (12-24 months) Blast phase (3-6 months)
What is the treatment for CML?
Imatinib
What is Imatinib fails?
SCT
Or new oral tyrosine kinase inhibitors: Dasatinib, Nilotinib, Bosutinib, Ponatinib
If a patient stops taking CML meds what will likely happen?
The patient will likely progress to acute leukemia
Which myeloproliferative neoplasm has a JAK2 mutation in nearly ALL cases?
Polycythemia Vera
What are some clinical findings of PV?
HSM Ruddy faces H/a Budd-Chiari syndrome Gout
Is EPO decreased or increased in PV? Why?
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
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
Most likely Acute Myeloid Leukemia
Specifically Acute Promyelocytic Leukemia
What cytogenetic abnormality is commonly assoc with APL?
t(15;17)
Produces PML-RARa fusion product
What functional defect is associated with product of PML-RARa fusion gene?
A block in terminal differentiation due to retinoic acid receptor disruption
RA is important for myeloid maturation – arrest at promyelocyte stage
What is the common therapy for PML?
ATRA (all-trans retinoid acid)
Which cytogenetic abnormality has a similar prognostic significance to t(15;17) in a patient with AML?
t(8;21)*** answer
inv(16)
t(15;17)
All have favorable prognoses
11q23 has an intermed/unfavorable prognosis
76 yo female with weakness and pancytopenia
Hypercellular BM with frequent hypogranular and hypolobated neutrophils
Small, hypolobated megakaryocytes
Myelodysplastic Syndrome
What is the most important diagnostic criterion for differentiating a myelodysplastic syndrome from an acute myeloid leukemia with myelodysplasia-associated changes?
The bone marrow blast percentage
>20% = AML <20% = MDS
What are some chromosomal abnormalities associated with MDS?
Monosomy 5 or del5q
+8
Monosomy 7 or del7q
In 50% of patients
What is the therapy for MDS?
Supportive care + growth factors
SCT
Hypomethylating agents
Lenalidomide
Histone Deacetylase Inhibitors
What is the name of the hypomethylating agent we should know? What is their mechanism of action?
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
What are blasts in MDS likely to be positive for on flow cytometry?
CD34, CD117, CD13, CD33
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 +
AML
Common clinical presentation of acute leukemias
HSM, PAINLESS LAD, skin involvement, testicular involvement, bone pain
THROMBOCYTOPENIA
ALL (children <20)
AML (adults 30-60)
What are some good prognostic cytogenetic classifications of AML?
t(8;21)
inv(16)
t(15;17)
Or with FAB type M3
What are some BAD prognostic cytogenetic classifications of AML?
Any patient with adverse karyotypic abnormalities (-5,-7, del(5q), abn(3q), complex or resistant disease
What is the therapy for AML?
Induction: 7 + 3 with Ara-C + Daunorubicin
Consolidation: HIDAC or Ara-C
60 yo male Fatigue and night sweats Hemoglobin 11 gm/dl Exam: spleen palpable 4cm at MCL Labs: otherwise unremarkable Teardrop cells
Primary myelofibrosis (PMF)
What common mutation is associated with PMF?
JAK2 mutation (in about 50%)
What is a possible treatment being explored for PMF?
JAK2 inhibitors
