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63 Cards in this Set
- Front
- Back
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What are some sx of CML?
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Fatigue,fevers, sweats, anorexia, weight loss, abdominal fullness, early satiety
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What are some physical exam findings of CML?
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Hepatoslenomegaly
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Is lymphadenopathy a common finding w/ CML?
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NO
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What are some common lab findings in CML?
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Leukocytosis of granulocytes from blasts to fully mature PMNs, basophila, eosinophilia, anemia, thrombocytosis, low leukocyte alkaline phosphatase (LAP)
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What is the pathophysiology of CML?
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t(9,22) creates fusion gene product bcr-abl (Philly Chr)
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Give a ds that is an exception to the two hit hypothesis of cancer.
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CML (the Philly chr is sufficient for ds expression)
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How does the BCR-ABL fusion lead to CML?
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It is a constiuitively active tyrosine kinase that activates downstream signaling in HSCs that lead to increased proliferation and decreased apoptosis.
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What is the best screening test for CML?
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FISH
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What is the tx of choice for CML?
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Imatinib (Gleevec)
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What are the two most common forms of resistance to Imatinib (Gleevec)?
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1. Amplification/over-expression of BCR-ABL (e.g. duplication of Ph chr)
2. Point mutations in the kinase domain of BCR-ABL that block binding --> MOST COMMON CAUSE OF RESISTANCE |
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What is the most sensitive technique for detecting BCR-ABL?
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Quantitative PCR
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What are the theraputic options for CML?
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1. ABL Tyrosine Kinase inhibitors (Imatinib, Nilotinib, Dasatinib)
2. Allogenic Stem Cell Transplantation |
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How can you tell primary from secondary resistance to Imatinib?
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Primary --> Inadequate initial response
Secondary --> Loss of previous response |
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What are some causes of primary resistance to Imatinib?
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1. Low levels of drug (non-compliance, metabolism, etc.)
2. Reduced hOCT1 levels (this is an influx pump) |
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What are some causes of secondary resistance to Imatinib?
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1. Overexpression/amplification of BCR-ABL (10%) --> just increase dose
2. Mutations w/in the ABL kinase domain (50-90%) |
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What is the only curative option for CML?
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Allogenic stem cell transplant
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Describe a peripheral blood smear of a CML pt.
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Looks like marrow:
Numerous immature granulocytes (from immature to fully developed) 2. Increased basophils |
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How can you distinguish benign neutrophilia from CML?
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Two ways:
1. In BN, the left shift isn't as marked as in CML. 2. LAP score is decreased in CML and normal to increased in BN |
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CD45 cell type
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common to all nl leukocytes
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Describe a bone marrow biopsy in CML.
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HETEROGENEOUS mix of maturing granulocytes and loss of fatty deposits
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What are some risk factors for CLL?
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1. Familial --> family member has 2-7x risk of ds
2. Environmental --> Agent Orange, pesticides, etc. |
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Tcell CD markers
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1-5, 7, 8
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granulocyte CD markers
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13, 15
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monocyte CD markers
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14
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Bcell CD markers
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19-23
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myeloid CD marker
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33
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stem cell (blast) CD marker
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34
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what are the characteristics that flow cytometry can assess
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size (forward scatter), complexity (side scatter), and immunophenotype (fluorescently labeled Abs)
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What are some common sx of CLL?
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fatigue, sweats, fever
wt loss/ anorexia early satiety FREQUENT INFECTIONS (sinopulmonary, encapsulated bacteria) |
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What are some common lab findings in CLL?
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Leukocytosis (LYMPHOCYTOSIS)
Anemia Thrombocytopenia Hypogammaglobulinemia |
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What are some common PE findings in CLL?
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LYMPHADENOPATHY
Splenomegaly Hepatomegaly in advanced ds |
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What are common comorbidities assoc w/ CLL?
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AIHA (10-25%), ITP (2%)
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What is Richter's transformation?
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The transformation of CLL to diffuse large cell lymphoma. It happens in 2-9% of CLL cases and is assoc w/ worsening sx.
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What does BCL-2 do?
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It inhibits apoptosis by inhibiting release of Cytochrome C from mitochondria. It is overexpressed in CLL.
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What is the staging system in CLL?
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The RAI classification system
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What does Stage 0 CLL imply?
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Lymphocytosis only (median survival > 15 yrs)
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What does Stage 1 CLL imply?
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Lymphocytosis and Lymphadenopath (median survival 8 yrs)
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What does Stage 2 CLL imply?
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Lymphocytosis and Splenomegaly (median survival 6 yrs)
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What does Stage 3 CLL imply?
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Lymphocytosis and Anemia (median survival 3 yrs)
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What does Stage 4 CLL imply?
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Lymphocytosis and Thrombocytopenia (median survival 2 yrs)
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Is CML curable?
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Yes, with allogenic SCT.
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Is CLL curable?
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No.
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When do you treat CLL?
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As the stage and symptoms dictate.
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What are some risk factors for AML?
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prior radiation or chemo (alkylating agents, topo ii inhibitors), benzene exposure, prior hx of MDS
Familial syndromes: Down, Fanconi anemia, Wiscott-Aldrich, etc. |
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What is the immunophenotype of CLL cells?
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mature B-cells CD5+, CD23+, CD19+, CD20+, light chain restricted (only kappa or lambda)
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What are some common cytogenetic findings in CLL?
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1. Deletion of 13q14 (>50% of cases)
2. Deletion of 11q23 & 17p13 are BAD. 3. Trisomy 12 found in ~20% of cases is bad. |
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What are some common clinical sx of AML?
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Hypermetabolic sx, anemia (severe), neutropenia (severe), thrombocytopenia, hyperleukocytosis, hepatosplenomegaly
Acute DIC (in APL) Leukemia cutis (indurated red plaques on extremities) |
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What is a Class 1 mutation? What is a classic example in AML?
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Mutation that confers a survival and/or proliferative advantage (FLT-3)
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What is a Class 2 mutation? What is a classic example in AML?
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Mutations that lead to a block in hematopoietic differentiation (PML-RARa)
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What is the most common cytogenetic abnormality seen in APL?
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t(15;17) PML-RARa fusion gene which acts as a transcriptional repressor
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What is a bad cytogenetic abnormality in AML?
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monosomy 5 or 7
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What is the typical induction therapy for AML?
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"7+3"
7 days of pyrimidine analog (Cytababine) 3 days of anthracycline (danurubicin, doxyrubicin, etc.) |
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What is the main therapy for APL?
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Induction chemo + all-trans retinoic acid (ATRA)
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What is a morphological feature of AML that is basically diagnostic?
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Auer rods
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What immunophenotype is diagnostic of APL?
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CD34- and HLADR-
These are seen on all blast cells except promyelocytes |
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How can you distinguish CLL from Mantle Cell Lymphoma?
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CLL is CD5+ and CD23+
MCL is CD5+ but CD23- |
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What is the median age of dx for ALL?
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11 (most common cancer in kids)
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What are some unique clinical sx of ALL?
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Tumor Lysis Syndrome (from increased cell turnover) -> renal failure
(Anterior) Mediatstinal Mass (T-Cell ALL) CNS involvement --> prevention is cornerstone of tx Testicular involvement --> strong predictor of CNS involvement |
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What are some common mutations in ALL and how do they change the prognosis?
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t(9;22) - Ph Chr --> BAD
abn(11q23) --> BAD Hypoploidy --> BAD t(12;21) - TEL-AML1 --> GOOD Hyperploidy --> GOOD |
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How does age affect the prognosis of ALL?
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< 1 or >= 10 is BAD
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Describe the BM aspirate in ALL.
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Large cells, open chromatin, prominent nucleoli
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Give the immunophenotype of B-Cell ALL.
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CD19+, CD10+, TdT+
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Give the immunophenotype of T-Cell ALL.
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CD1a, cytoplasmic CD3
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