Term
What do each of the following genetic abnormalities tell you about a patient's prognosis?
1) All-trans retinoic acid (ATRA) in acute promyelocytic leukemia
2) Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)
3) Fms-like tyrosine kinase 3 (FLT3) internal tandem duplications (ITD) in acute myeloid leukemia |
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Definition
1) Reduced early death rate and impacted overall survival
2) Imatinib shows improved response in more unfavorable sub-group.
3) Unfavorable clinical course- use of FLT3 inhibitors |
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Term
| How can immunphenotypic characterization guide therapeutic use of monoclonal antibodies in hematologic malignancies? |
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Definition
1) Anti-CD20 (Rituximab) for B cell lymphoid malignancy
2) Anti-CD52 (Alemtuzumab) for T cell leukemia/lymphoma
3) Anti-CD30 (Brentuximab vedotin)- Hodgkin lymohoma, anaplastic large cell lymphoma
4) Anti-CD33 (Gemtuzumab ozogamicin)- AML (withdrawn in 2010) |
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Term
| What are the major indications for bone marrow evaluation? |
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Definition
1) Unexplained cytopenia (Anemia, TP, Leukpenia)
- concern for acute leukemia (meloid or lymphoblastic)
- also could be B12/folate, toxic, infection, immune (aplastic anemia)
2) Persistent elevated counts
- Chronic lymphoid/myeloid leukemia
3) Lymphadenopathy
- Lymphoma
4) Splenomegaly
- Lymphoma
5) Circulating blasts
- Acute leukemia concern
- Sometimes seen in infants under stress of patients taking G-CSF |
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Term
| What is the difference between a "lymphoma" and a "leukemia"? |
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Definition
1) Leukemias primarilly affect bone marrow with blood and marrow involvement at diagnosis.
- Can be lymphoid or myeloid
2) Lymphomas affect lymph nodes and other lymph sites (Spleen, ect).
- Suspicious if you see lymphadenopathy/splenomegaly
- ALWAYS LYMPHOID (Hodgkin and non-Hodgkin types ) and B>>>T |
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Term
| Where are most bone marrow biopsies taken from? |
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Definition
| Axial bones in adults- Posterior superior iliac crest |
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Term
| What are the primary components of a bone marrow evaluation? |
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Definition
1) Peripheral blood smear (cytomorphologic features can be clues)
- Red cells, leukocytes and platelets
- Circulating blasts (high nuclear:cytoplasmic ratio seen in acute leukemia). If Auer rods presents, it is AML
- Abnormal lymphoid cells (chronic lymphoid leukemia)
2) Bone marrow aspirate smear (Wright-Giemsa stain)
- Fine cytological detail
- Manual differential precursor count
- Prussian blue for iron
3) Bone marrow biopsy (architectural assessment, cellularity and cell distribution)
- Ideal for involvement of focal processes such as carcinoma, lymphoma and granuloma
4) Ancillary studies
- Flow cytometry (acute leukemias and mature B-cell neoplasms (chronic B-lymphoid leukemia and B-lineage non-Hodgkin lymphoma)
- Cytogenetic (Karyotyping and FISH)
- Molecular (PCR-RTPCR)- Immunoglobulin heavy chain gene (IGH) and T-cel receptor (TCR) chains frequently utilized to demonstrate clonality. |
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Term
| What types of genetic alterations are typically associated with hematological malignancies? |
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Definition
| Mutations, translocations or inversions of chromosomes containing genes whose products regulate proliferation (cell cycle, differentiation, ect.) |
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Term
| How are Lymphomas generally characterized? |
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Definition
Rate of Proliferation
1) low growth fraction
- Follicular Cell Lymphoma-BCL2 translocation
2) high growth fraction
- Burkitt’s Lymphoma-c myc translocation |
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Term
| What are the major types of leukemia? |
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Definition
1) Acute: represent arrested stages of differentiation (accumulation of immature cells)
- Rapid progression and early death if untreated
- ALL
- AML
2) Chronic: increased production and lack of apoptosis (accumulation of differentiated cells)
- CLL
- CML |
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Term
| Describe the current WHO classification system for myeloid hematological malignancies. |
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Definition
Stratified by cell of origin.
1) Myelodysplastic syndromes
- pancytopenia
- ineffective hematopoiesis
- dysplastic bone marrow changes
- significant risk of progression to acute myeloid leukemia
2) Myeloproliferative Neoplasms
- unregulated, sustained, excess production of one or more mature peripheral blood elements with intact maturation and minimal dyspoiesis
3) Myelodysplastic/Myeloproliferative neoplasms |
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Term
| Describe the current WHO classification system for Lymphoid hematological malignancies. |
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Definition
Based upon cell of origin and site in the body
1) B-cell
- Precursor B-lymphoblastic leukemia/lymphoma
- Mature B-cell neoplasms
2) T-cell
- Precursor T-lymphoblastic leukemia/lymphoma
- Mature T/NK neoplasms
3) Hodkin's |
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Term
| Describe the basic pathophysiology/progression of Chronic Myeloid Leukemia. |
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Definition
1) CML involves transfer of ABL1 oncogene to BCR on 22q resulting in abnormal tyrosine kinase activity (called "Philadelphia Chromosome")
- causes transformation of a hematopoietic progenitor into a malignant clone
2) There are possible chronic, accelerated and blast crisis stages
3) Gleevec (imatinib mesylate) is the first tyrosine kinase inhibitor that is commercially available for clinical use in CML |
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Term
You suspect that your patient is anemia, since they are fatigued, weak and somewhat confused. You order a peripheral blood smear and see the following:
1) Absolute neutropenia
2) TP
3) Blast cells in circulation
Why are you concerned? |
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Definition
| These findings are consistent with an acute leukemia. You would need a bone marrow |
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Term
| How do the peripheral blood findings associated with chronic leukemia differ from those found in acute leukemia? |
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Definition
1) Acute
- Cytopenia
- Blast cells
2) Chronic
- No cytopenia
- Elevated WBC (lymphocytosis)
- May be associated with erythroblastosis (nucleated RBCs) |
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Term
| What is Leukoerythroblastosis and what does it indicate? |
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Definition
“Leukoerythroblastosis” is an abnormal peripheral blood film finding that indicates bone marrow infiltration and replacement.
Look for nucleated RBCs and teardrop cells in peripheral blood. |
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Term
Patient presents complaining of enlarged lymph node that is resistant to antibiotic treatment.
Describe a basic workup. |
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Definition
1) LN biopsy (extra-nodal proliferation)
- If benign
- If malignant, think Lymphoma or Metastasis
2) If Lymphoma
- Hodgkins (lymphoma with Reed-Sternberg cells surrounded by reactive non-neoplastic chronic inflammatory cells )
- Non-Hodkins |
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Term
| WHat is the immunophenotype of classic Hodkin's lymphoma? |
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Definition
Could be Nodular Sclerosis, Lymphocyte-rich, Mixed cellularity or Lymphocyte depleted
- B-cell & T-cell antigen negative
- CD15/LeuM1+
- CD30/Ki-1+
- CD45/LCA- |
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Term
What type of classic Hodkin's Lymphoma is described by each of the following?
1) Birefringent collagen bands and "lacunar" type RS variants
2) Numerous small lymphs
3) Moderate number of classic RS cells with other inflammatory cells
4) Very numerous RS cells and/or extensive diffuse fibrosis |
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Definition
1) Nodular sclerosis
2) Lymphocyte-rich
3) Mixed cellularity
4) Lymphocyte depleted |
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