WBC Disorder Cases - Olteanu & Atallah Flashcards
What is the mechanism of action of imatinib?
Name some other tyrosine kinase inhibitors used clinically to treat CML
Tyrosine kinase inhibitor: Binds near ATP binding site of bcr-abl, prevents TK signaling
Dasatinib
Nilotinib
Bosutinib
Ponatinib
If a patient, otherwise in remission, decides to stop taking nilotinib for their CML, what will likely happen?
Is this always true?
CML will return
Not necessarily true - the existence of true ‘molecular remission’ is currently under investigation
Combined JAK2 mutation and peptic ulcer disease is likely indicative of what?
polycythemia vera
What is the main treatment for AML with t(15;17)?
What is the approximate cure rate with this drug?
Why don’t the others respond to therapy?
What is usually combined with ATRA to enhance its therapeutic effect?
ATRA (All Trans Retinoic Acid)
90% cure rate
The remaining 10% usually dies from DIC before ATRA treatment can take effect
arsenic trioxide (more favorable side effect profile, according to wiki)
Describe the general rationale behind hypomethylating agents. Name one.
Decitabine (hypomethylating agent)
Rationale: hypermethylation of DNA prevents expression of genes needed to mature developing cells, resulting in pancytopenia (among other things). De-methylating agents allow gene expression and the maturation of chronically immature cell populations
In a patient with WBC: 80K and Blasts: 60K, why would normal fibrinogen be important?
What if flow cytometry and immunohistochemistry reveals the following (picture)?
Normal fibrinogen indicates that the patient likely does not have APL -> the differential is AML or ALL…
AML
What is the median age of presentation for AML?
~60 years old
What is the most common cytogenetic classification of AML?
What others are there?
“Standard” i.e. no specific translocations (51%)
Others include: t(8;21), t(15;17), inv(16), FAB type M3 (28%)
“Poor” - adverse karyotypic abnormalities (i.e. -5, -7, del(5q), qabn(3q)), or resistant disease (20%)
What is 7 + 3 therapy?
What is it used to treat?
Is this an effective treatment?
Ara-C (7 days) + Daunorubicin (3 days)
Inductive therapy for treatment of AML
Not really. It has a high mortality rate (~10%) and depends on the hope that if you kill off most of the bone marrow, the stuff that grows back will be ‘good’ marrow.
What is the approximate prevalence of JAK2 mutations in the following myeloproliferative neoplasms (MPNs)?
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis
- 100%
- 50%
- 50%
Teardrop cells, with splenomegaly, fatigue, cachexia, bone pain, and night sweats is indicative of what?
myelofibrosis
What is the difference between a lymphoma and leukemia?
In leukemia, cancers cells arise from the bone marrow and are in the blood
In lymphoma, cancers cells arise from the lymphatics and are more solid tumors.
What is the difference between a myeloid leukemia and lymphoid leukemia?
The derivatives of the cancer cell! Myeloid leukemias come from myeloid derviatives
What are the four major types of B cell cancers?
What are their markers?
Mantle Cell Lymphoma
- CD5+
- FCM7+
Chronic Lympocytic Leukemia
- CD5+
- CD23+
Follicular Lymphoma
- CD5-
- CD10+
MALT lymphoma
- CD5-
- CD10-
What are some prognostic indicators for Chronic Lymphocytic Lymphoma?
Good
- Low RAI stage
- Mutated IGHV gene
- 13q deletion
Bad
- High RAI stage
- Unmutated IGHV gene
- CD38/ZAP70 expression
- 11q, 17p deletion
What is the RAI system?
What are its stages?
Staging system for leukemias/lymphomas
Stage 0: lymphocytosis
Stage 1: stage 0 + adenopathy
Stage 2: stage 1 + organomegaly
Stage 3: stage 2 + anemia
Stage 4: stage 3 + thrombocytopenia
What are some indications to treat CLL?
Lymphocyte doubling time <6 months
Hemoglobin <10g/dL
Platelets <100k/uL
Autoimmune anemia or thrombocytopenia
Enlarged Lymph nodes
Richter Transformations
Night sweats, weight loss, and fever
Hairy cell Leukemia
Who does it normally affect?
What is seen on a blood smear?
Normally affects middle-aged men
Lymphocytes with hairy projections that stain positive for TRAP, and a lack of other cell types
Hairy Cell Leukemia
What are clinical symptoms?
What is seen on flow?
splenomegaly and fibrosis of the marrow
CD22 and CD11c
Sezary Syndrome
Describe the cells
What are associated disorders?
T cells with a cerebriform nucleus
CD4+
Mycosis fungoides, erythroderma
Adult T cell Lymphoma/Leukemia
Describe the cells
What are associated disorders?
CD4+ T cell with “flower like” nucleus
HTLV-1 infection, Hypercalcemia
Large Granular Lymphocytic Leukemia
What cell is involved?
How does it present?
What is it associated with?
Cytotoxic T cells
Splenomegaly, neutropenia, anemia
Autoimmune diseases
What is the proliferative disorder called for
Mast cells
RBCs
Platelets
Eosinophils
Neutrophils/Monocytes
Systemic Mastocytosis
Polycythaemia vera
Essential Thrombocythaemia
Chronic eosinophilic leukemia
CML or Primary myelofibrosis
What characterizes a myeloproliferative disorder?
How is it different from a myelodysplastic disorder?
Hypercellular bone marrow with working hematopoiesis leads to cytosis
In MDS, the bone marrow is hypercellular, but hematopoiesis is broken leading to cytopenias
CML
What age is most commonly diagnosed?
What are the clinical findings?
40-60 years old
Heptosplenomegaly, fatigue, weakness, weight loss, anorexia
What causes CML? How is it treated?
What is seen on the blood smear?
Expansion of pluripotent stem cells due to BCR-ABL fusion gene. TK inhibitors or stem cell transplant will cure.
Leukocytosis (with immature myeloid) with basophilia
What are the three stages of CML?
What happens in the end phase?
Chronic phase (3 years), Accelerated Phase (1 year), Blast phase
disease progresses to either AML or ALL
What causes polycythaemia vera?
What is seen on the blood smear?
expansion of pluripotent stem cells due to JAK2 mutation.
Increased RBCs along with raised numbers of granulocytes and platelets.
What are clinical symptoms of polycythaemia vera?
What causes them?
- Splenomegaly- hematopoiesis outside of bone
- thrombosis- over production of platelets and RBCs
- Gout- increased uric acid from increased cell death
- Peptic ulcer, heat urticaria, ruddy face- increased histamine from mast cells
What distinguishes polycythaemia vera from non-pathologic RBC expansion?
Low EPO
High SaO2
How is polycythaemia vera treated?
What can polycythaemia vera evolve to?
phelobotomy to remove extra cells
15-20% to “spent phase” similar to PMF
2-3% to AML or MDS
