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70 Cards in this Set
- Front
- Back
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neoplasms of hematopoietic cells are...
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Leukemias
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Chronic/Acute distinction of leukemias denotes...
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...speed of clinical manifestation.
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ALL is a malignancy of a ....
In ALL, malignant cells largely lose the... |
committed lymphoid progenitor cell (pre-T or –B cell).
... ability to differentiate. |
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Are malignant cells morphologically heterogenous in ALL?
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No, homogeneous.
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Leukemia means that there is significant _____ & ______ involvement with the disease.
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peripheral blood and BM
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ALL is a malignancy of a....
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... committed lymphoid progenitor cell (either B or T)
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In either type of ALL, what have the malignant cells lost?
What do we see as a result? |
The ability to differentiate.
A morphologically homogeneous population of lymphoblasts. |
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CLL is a malignancy of...
Cells are a morphologically _____ population of ______ _________. Do the cells look like blasts? |
...mature B-cells.
homogeneous mature lymphocytes No! Not at all. |
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AML is a malignancy of...
What is seen morphologically? Why? |
...a committed myeloid progenitor cell.
homogeneous pop. of myeloblasts the cells have lost their ability to differentiate. |
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If you have Auer Rods present in a blast, it has to be...
What are Auer Rods? What do they look like? |
... a myeloblast --> AML
FUSED lysosomes/granules in a cell that is ultimately meant to produce granules. Needle-shaped pink thing. |
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Does all AML have Auer Rods?
Does ALL have Auer Rods? |
No.
No, you will NEVER see them. |
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Which leukemia is technically a myeloproliferative disorder?
Where is the 'lesion' in CML? |
CML
In the pluripotent progenitor cell; before it has differentiated into either a committed lymphoid progenitor or a committed myeloid progenitor. |
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In which leukemia do the malignant cells maintain the ability to differentiate?
Which pathway do they preferentially take? Do they take other paths too? What is seen morphologically? |
CML
the myeloid pathway. Yes. Cells @ all levels of differentiation in the marrow and the peripheral smear as well. |
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What is the epidemiology of CML:
Incidence Risk Factors Male/Female Ratio Mean Age of Diag. |
1 / 100,000
Ionizing rad. exposure 1.4m : 1.0f 66yo |
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Is it common to see CML in pediatric populations?
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No it is uncommon, though it IS possible.
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Which class of leukemias can manifest incidentally? Is there cross-over?
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The chronic ones.
No, the acute ones will never manifest incidentally. |
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Common Lab Values in CML?
Px? Is it often found incidentally, i.e., w/o symptoms? |
Leukocytosis (neutrophilia, basophilia, eosinophilia)
Anemia Thrombocytosis Px: fatigue, sweats, fevers, splenomegaly, hepatomegaly, weight loss Yes. |
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With the myeloid diseases is lymphadenopathy common?
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no, it is exceedingly rare.
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How can you distinguish CML from P vera re: lab values?
Which typically contributes the *most* to the very high WBC count in CML patients: PMN, Basophils, eosinophils |
P vera will show erythrocytosis
CML patients can be anemic PMNs. |
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What fuels the pathogenesis of CML?
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The (Ph) Philadelphia Chromosome
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(Ph) is a translocation b/t...
present in ___% of CML cases by conventional cytogenetics. What about the remainder? |
...t(9;22)
95% 5% harbor cytogenetically silent translocations that must be detected by FISH. |
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Is Ph necessary for a Dx of CML?
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Yes.
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What is the product of Ph?
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BCR-ABL: a fusion protein w/ constitutive tyrosine kinase activity.
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Which part of BCR-ABL was a tyrosine kinase before translocation?
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ABL
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BCR-ABL is ______ and _____ to cause CML.
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necessary and sufficient
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What helps determine the phase of CML in Dx?
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peripheral smear review
BM aspirate & biopsy |
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If a CML patient with Ph is discovered with cytogenetic monitoring to have acquired a new, different mutation as well, what does this indicate?
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that the disease isn't being managed/controlled well.
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What is the best screening test for CML? Upsides? Downsides?
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FISH
will pick up 100% of Ph cases It will miss all other abnormalities b/c it is targeted |
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What is PCR useful for in CML?
Can it pick up additional clonal abnormalities? |
monitoring treatment efficacy (can detect as few as 1 in 100,000 cells.
No. |
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What are the 3 stages of CML? In it's end stages, which disease does it turn into?
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chronic, accelerated, blast crisis.
AML or ALL (usually AML but it *can* turn into ALL as well) |
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What are some Tx for CML?
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Imatinib
2nd generation BCR/ABL inhibitors Stem Cell Transplant |
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What does Gleevec (Imatinib) do?
How is it taken? Is it curative? Side effects? |
b/ the ATP binding pocket of BCR-ABL
Orally No Generally well-tolerated. |
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What is the standard of care for CHRONIC phase CML?
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Gleevec (Imatinib)
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Characterize and give 2 possible etiologies for both Primary and Secondary resistance to Imatinib.
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Primary:
Inadequate initial response - low trough lvls of drug (noncompliance, absorption/metabolism issues) - reduced hOCT1 lvls (imatinib influx pump) Secondary: Loss of previous response - amp / overexp of bcr-abl (10%) - mut w/i kinase domain (90%) |
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GVHD upon allogeneic SCT is associated with ____ risk of relapse in CML patients?
How about if you deplete the graft of T-cells? |
decreased.
increased. |
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CML patients who relapse after SCT can be put back into remission with....
This is evidence of what type of effect? |
... donor lymphocyte infusions.
Graft versus leukemia effect |
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What is the most common adult leukemia?
What is the median age of Dx? Are there exceptions? |
CLL
72; low, you will never see a kid with CLL, it just does not happen. |
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Is there a family predisposition for CLL?
Are there any environmental agents that are associated with CLL? |
Yes
Agent Orange. |
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What types of infections are seen commonly with CLL?
Why? |
URI & LRI w/ encapsulated pneumococcus and h. influenzae
These patients have Hypogammaglobulinemia. |
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Label the following symptoms/findings with CLL, CML, or both:
Hepatomegaly Splenomegaly Lymphadenopathy Elevated Neutrophils Hypogammaglobulinemia Thrombocytopenia Thrombocytosis Frequent URI / LRI Fatigue sweats Fever abdominal fullness weight loss/anorexia Lymphocytosis |
CML: PMNs, thrombocytosis
CLL: Infections, Lymphadenopathy, Thrombocytopenia, Hypogammaglobulinemia |
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All the cells seen in the peripheral smears of CLL look like...
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...typical, mature lymphocytes.
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Autoimmune hemolytic anemia occurs in 10-25% of patients with...
How about immune thrombocytopenia (ITP) seen in 2%? |
...CLL
CLL |
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Can CLL evolve to a more aggressive lymphoid neoplasm? Is this new neoplasm clonally related to CLL?
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Yes. Yes in 60% of cases.
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What is the most commonly talked about transfusion of CLL?
What are the Sx of this Transformation? What is another possible transformation? |
Richter's Transformation of CLL to diffuse large cell lymphoma.
Worsening fevers, sweats, weight loss, lymphadenopathy, splenomegaly. Prolymphocytic leukemia |
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What does Bcl-2 inhibit? How?
Explain its significance in CLL |
apoptosis
Inhibits release of cytochrome c from mitochondria. Bcl-2 overexpression allows malignant cells to persist and accumulate over time. |
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How is Rai Staging of CLL clinically significant?
What do stage 4 patients have? Is CLL a curable disease? If a CLL patient is asymptomatic, do you treat? What are some indications for chemotherapy in CLL patients? |
Median survival is inversely related to stage.
Lymphocytosis and Thrombocytopenia No No. progression/worsening of any of the symptoms, autoimmune cytopenias, increased # of bact. inf. |
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AML is a disease of the elderly or young? Are there exceptions?
What are some risk factors for AML? |
...elderly. Yes.
Prior radiation, chemo (alkylating agents, topoisomerase II inhibitors) Benzene Prior history of MDS or a myeloproliferative disorder Familial syndromes (down, fanconi, bloom, etc) |
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Akylating agents & radiation can lead to AML w/i ___ years.
Topoisomerase II inhibitors? |
5-10 years
~2 years. |
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What are some clinical manifestations of AML? (4)
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NEUTROPENIC - often severe
anemic - often severe thrombocytopenia - often severe Hyperleukocytosis - mental status changes, dyspnea bilateral infiltrates due to stasis of blood flow |
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In which type of AML is Acute DIC most common?
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acute promyelocytic leukemia (APL)
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DIC in acute leukemia: which is more likely, AML or ALL?
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AML (APL to be specific).
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Extramedullary involvement: CNS, gums, leukemia cutis .... seen often in AML or CML?
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AML
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2 classes of ACUTE leukemia mutations:
Class 1 mutations....(& give 2ex.) Class 2? (1ex) |
confer a survival and/or proliferative advantage
- BCR-ABL --> ALL - FLT3 lead to a block in hematopoietic cell differentiation - PML-RARa --> PML |
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FLT-3 is a _____ _____ ______ that is seen in ~30% of adult ____ cases.
Common mutation makes it... |
receptor tyrosine kinase; AML
... constituitively active. |
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RARa is normally involved in transcription of genes necessary for...
The translocation mutant PML-RARa is central to the pathogenesis of which type of leukemia? How does the mutant work? Tx? |
...hematopoiesisi / differentiation.
APL fuctions as a transcriptional repressor blocking hematopoietic differentiation. doses of retinoids (all-trans retinoic acid) can release inhib. of transcription and promote differentiation. |
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t(15;17) is associate with better or worse cure rates?
Old age? Deletions of chromosomes 5 and 7? AML arising from a prior history of MDS/myeloprolif? AML related to treatment of a disease? |
better
worse worse worse worse |
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Is AML a curable disease? Rate?
How is it treated and with what goal in adults? Younger? In high risk disease, what should be considered upon first remission? |
yes! 30-40%
7 + 3 Chemotherapy, complete remission Consolidation; eradication of minimal residual disease (Cure) Allogeneic SCT |
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What is 7 + 3 chemo?
Consolidation Therapy? Which leukemia are they used in treating? |
7 days of the pyrimidine analog, cytarabine (Ara-C).
3 days of an anthracycline (daunorubicin, idarubicin). high-dose cytarabine for several cycles AML |
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How is APL treated? Cure rate?
Do we consider SCT? |
all trans retinoic acid (ATRA)
>80% Only for relapsed/refractory disease. |
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ALL is common/uncommon? Disease of young or elderly?
Prog. in young? old? <1yo? > 50x10^9 WBC @ presentation? t(12;21)? t(9;22)? |
very uncommon
young (11 yo median) excellent. Bad. bad. worse better worse |
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What is the most common cancer in children?
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ALL.
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What is Tumor lysis syndrome?
Which leukemia does it preferentially occur in? Tx? |
life-threatening manifestation of high cell turnover... the products of the lysed cells are being released
- hyperuricemia - hyperkaliemia (--> arrythmias) - hyperphosphatemia - hypocalcemia - high LDH can cause acute renal failure due to uric acid deposition ALL moreso than AML hydration, allopurinol, rasburicase |
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Are most Sx of ALL similar to AML?
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yes.
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Lymph node involvement is LESS common in ALL or AML?
Mediastinal mass is more likely in which form of what leukemia? |
AML
precursor T-cell ALL |
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What is a strong predictor of CNS involvement/relapse in males with ALL?
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Testicular involvement.
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Prevention of CNS relapse is a cornerstone of treatment of which acute leukemia?
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ALL (intrathecal chemo, cranial radiation)
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What is the most common abnormality in adult B-cell ALL? What is it called? Gives rise to which fusion gene?
Childhood B-cell ALL? Gives rise to which fusion gene? |
t(9,22), Ph, BCR-ABL
t12;21), TEL-AML1 --> abnormal NCoR recruitment --> repression of AML1-mediated transcription |
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Prednisone (PRED), Vincristine (VCR), Daunorubicin, L-Asparaginase (L-ASP) form the backbone of induction therapy for which leukemia?
Cure rate in kids? Adults? |
ALL
80% 30-40% |
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Is imatinib by itself a useful therapy in Ph+ adult ALL? How about in conjunction w/ typical induction therapy?
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No.
Yes. |
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See blasts, think what?
mature lymphs? spectrum of myelopoieisis? DIC? Blasts + ant. mediastinal mass? Are Dx tests necessary for accurate Dx/classification of these disorders? |
AML or ALL
CLL CML AML T-cell ALL Yes. |
