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259 Cards in this Set
- Front
- Back
define adjuvant therapy and give an example of its use
|
treatment given to eradicate microscopic amounts of cancer that may remain after removal of a solid tumor (ie. breast CA)
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define induction therapy and give an example of its use
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treatment to induce remission for a cancer treated primarily with chemotherapy (ie. leukemia, lymphoma)
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define consolidation therapy and give an example of its use
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treatment given after induction therapy intended to produce sustained remission
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define neoadjuvant therapy and give an example of its use
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treatment used to shrink a tumor before it is removed or irradiated (ie. shrink a breast cancer to make it more easily resected)
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define palliative therapy and give an example of its use
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treatment given to attempt to shrink or stabilize an incurable cancer (most common usage of chemo). (ie. CLL or Multiple Myeloma)
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define direct local therapy and give an example of its use
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treatment given directly into an organ or cavity to deliver higher doses to a specific area (area may be protected from toxic substances - ie. CNS and BBB)(another example is liver)
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describe the phases of drug testing
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phase I - dose finding
phase II - looking for efficacy phase III - compare to Gold Standard phase IV - generic testing |
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MOA of Alkylating Agents?
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impair cell function by forming covalent bonds with biologically important molecules (ie. DNA, RNA, proteins)
*dependant on cell proliferation for activity* |
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MOA of antimetabolites?
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compete with normal metabolites for the catalytic or regulatory site of a key enzyme or by substituting fofr a metabolite that is normally incorporated into DNA or RNA
*works best in S phase* |
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describe the dose response curve for antimetabolites
- what does this mean? |
non-linear dose response curve
(beyond a certain dose no more cells are killed despite a higher dose of drug) |
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MOA of folate analog?
name of folate analog drug? |
prevents the reduction of folic acid to tetrahydrofolic acid by binding reversibly to dihydrofolate reductase
(methotrexate is prototype) |
|
reversal agent for methotrexate (folate analog)?
|
folininic acid
|
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when are folate analogs (methotrexate) used? (2)
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lymphomas
sarcomas |
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MOA of purine analogs?
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block purine/DNA synthesis by inhibiting ribonucleotide reductase
|
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Purine analogs are used in which two disorders??
|
CLL
Low grade lymphomas |
|
MOA of pyrimidine analogs?
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inhibits DNA polymerase - this is incorporated into DNA and causes strand breaks
|
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Pyrimidine analogs are used to treat? (3)
|
AML
Lymphoma MDS |
|
prototype pyrimidine analog?
|
cytarabine
|
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MOA of adenosine analogs?
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adenosine analog is resistant to metabolic inactivation by the enzyme adenosine deaminase. analog is incorporated into DNA causing strand breaks
|
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adenosine analogs are used to treat? (3)
|
Hairy cell leukemia
Waldenstrom's CLL |
|
MOA of substituted urea (hydroxyurea)?
|
blocks DNA by inhibiting ribonucleotide reductase
|
|
substituted urea (hydroxyurea) is used to treat? (4)
|
*chronic myeloproliferative disorders*
- CML -P.vera -E.T. - reduction of blasts in AML |
|
General toxicities of antimetabolite therapy?
|
1. GI
2. Marrow suppression 3. Neurotoxicity 4. Acute MI (5-FU) 5. nausea (mild xcept MTX) |
|
MOA of anthracyclines (antitumor antibiotic)
|
DNA intercalators insert between DNA base pairs - creates breaks in DNA strands.
- also interferes with topoisomerases (prevents re-litigation of strands during DNA replication) |
|
toxicities of anthracyclines? (3)
|
1. alopecia
2. cardiotoxic 3. chemical vessicants (tissue burns) |
|
MOA of Bleomycin?
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intercalates DNA at G-C and G-T sequences - causes free oxygen radicals that go on to cause strand breakage
|
|
Bleomycin is used to treat? (3)
|
1. Hodgkin's
2. testicular cancer 3. lymphomas |
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Toxicities of bleomycin? (4)
|
1. pulmonary fibrosis (O2 administration exascerbates)
2. flu-like rxn 3. anaphylaxis 4. hyperpigmentation |
|
MOA of vinca alkaloids?
|
M-phase specific alkaloids that bind to tubulin so that microtubules cannot polymerize. this impairs mitotic spindle formation
|
|
toxicities of vinica alkaloids? (3)
|
1. neurotoxicity
2. ileus 3. marrow suppression |
|
MOA of taxanes
|
promote assembly and stabilization of microtubules
|
|
what are the two classes of antimicrotubule agents?
|
1. Vinca Alkaloids
2. Taxanes |
|
what are the two classes of antitumor antibiotics?
|
1. Anthracyclines
2. Bleomycin |
|
MOA of steroids as chemotherapy?
|
directly toxic to lymphocytes and malignant lymphoid cells. thought to trigger apoptosis
|
|
steroids use to treat which malignancies? (4)
|
1. CLL
2. ALL 3. Myeloma 4. Lymphoma |
|
MOA of platinum compounds?
|
(technically considered alkylating agents)
produce DNA crosslinks which inhibit the synthesis of DNA, RNA and protien. |
|
platinum compounds used to treat? (2)
|
1. many solid tumors (lung, breast, testicular)
2. refractory lymphomas, acute leukemias |
|
toxicities of platinum compounds? (3)
|
1. nephrotoxic
2. vomiting 3. myelosuppression |
|
MOA of L-Asparaginase?
|
depletes tumor cells of asparagine (an AA needed for protein synthesis). normal cells can synthesize asp intracellularly and are therefore spared the toxicity.
|
|
L-Asparaginase is used to treat? (1)
|
ALL
|
|
toxicities of L-Asparaginase? (2)
|
1. hypersensitivity
2. pancreatitis |
|
MOA of Rituxumab?
|
anti-CD20 monoclonal antibody that binds compliment - causes compliment and Ab dependant cellular cytotoxicity by directly inducing apoptosis
|
|
rituxumab used to treat?
|
multiple B cell malignancies
- must be CD20 positive |
|
1. the body normall produces IFN-alpha in response to?
2. what cells produce it? |
1. viral infections
2. lymphocytes |
|
MOA of recombinant IFN-alpha used for chemotherapy?
|
direct anti-viral activity.
- increases expression of MHC and tumor associated antigens. - also increases NK function |
|
IFN-alpha is used to treat which cancers? (4)
|
1. chronic phase CML
2. maintain remission in myeloma 3. kidney cancer 4. melanoma |
|
MOA of Imatinib mesylate (Gleevec)?
|
Tyrosine kinase inhibitor
- Bcr-Abl fusion protein acts as a tyrosine kinase which transforms normal cells to malignant ones. Imatinib stops this by inhibiting this specific tyrosine kinase. |
|
Imatinib is used to treat? (3)
|
1. chronic and accelerated phases of CML
2. GI stromal tumors 3. Ph positive ALL |
|
MOA of thalidomide?
|
anti-angiogenesis factor
|
|
thalidomide is used to treat? (2)
|
1. myeloproliferative disorders
2. myeloma |
|
MOA of Bortezomib?
|
26S Proteosome inhibitor
- prevents proteolysis - disrupts signal cascades within cell |
|
Bortezomib is the 2nd line treatment for?
|
Myeloma
|
|
MOA of All-Trans Retinoic Acid?
|
induces maturation in APL cells (t15;17)
|
|
toxicities of All-Trans Retinoic acid? (2)
|
1. RA-APL Syndrome (25%)
- fever, dyspnea, wt. gain, lung infiltrates 2. leukocytosis (40%) |
|
what is the treatment for RA-APL syndrome?
|
steroids
|
|
what is Neupogen and what is it used for? (4)
|
Neupogen is G-CSF: a recombinant DNA product which contains the G-CSF gene
It is used to: 1. treat chemo induced myelosuppression 2. supplement BMT 3. assist with stem cell collection 4. treat chronic neutropenia |
|
what is the name for the recombinant GM-CSF and what is it used for?
|
Leukine
used for AML and allo or auto transplants |
|
What is Neumega and what is it used for?
|
Megakaryocyte stimulating factor (IL-11)
used to treat post-chemotherapy thrombocytopenia |
|
Cyclophosphamide:
What type of drug is it and what is it used to treat? (4) |
Alkylator
used to treat: - lymphoma - breast CA - CLL - Lymphoblastic anemia |
|
Nitrogen Mustard:
1. What type of drug is it and 2. what is it used to treat? |
1. Alkylator
2. Hodgkins lymphoma |
|
Azacitadine:
1. What type of drug is it and 2. what is it used to treat? (2) |
1. antimetabolite
2. MDS, AML |
|
Chlorambucil:
1. What type of drug is it and 2. what is it used to treat? |
1. alkylator
2. CLL |
|
Mephalan:
1. What type of drug is it and 2. what is it used to treat? |
1. alkylator
2. multiple myeloma |
|
Epirubicin:
1. What type of drug is it and 2. what is it used to treat? (3) |
1. antitumor antibiotic
2. breast, AML, esophagus |
|
Capecitabine:
1. What type of drug is it and 2. what is it used to treat? (2) |
1. antimetabolite (pyrimidine analog)
2. breast and colon CA |
|
Doxorubicin:
1. What type of drug is it and 2. what is it used to treat? (4) (2) |
1. antitumor antibiotic
2. breast, lymphomas, Hodgkin's, bladder |
|
Gemcitabine:
1. What type of drug is it and 2. what is it used to treat? (3) |
1. antimetabolite (pyrimidine analog)
2. pancreas, breast, other GI |
|
Ifosfamide:
1. What type of drug is it and 2. what is it used to treat? |
1. alkylator
2. sarcoma, testicular cancers |
|
Danorubicin and Idarubicin:
1. What type of drug is it and 2. what is it used to treat? |
1. antitumor antibiotics
2. AML |
|
Mitoxantrone:
1. What type of drug is it and 2. what is it used to treat? (4) |
1. antitumor antibiotic
2. AML, ALL, prostate, lymphomas |
|
5-FU:
1. What type of drug is it and 2. what is it used to treat? (3) |
1. antimetabolite (pyrimidine analog)
2. colon, breast, other GI CAs |
|
Vincristine, Vinblastine, Vinorelbine:
1. What type of drug is it and 2. what is it used to treat? (5) |
1. Vinca Alkaloids
2. lymphomas, ALL, myeloma, Hodgkin's, other tumors (breast, lung, kidney) |
|
what must developing blood cells "undergo" before they are able to leave the bone marrow?
|
they must maneuver through the sinusoids
|
|
describe the fat content in the bone marrow in a young person vs. an old person?
|
as a person ages, fat in the bone marrow increases
rule: 100-age= % cellularity) |
|
what is the function of adventitial reticular cells?
|
promote hemostasis of the bone marrow and line the sinusoids
they determine whether developing blood cells function and can leave the bone marrow. |
|
where are most bone biopsies taken?
|
posterior iliac crest
|
|
what are the four hematopoietic stem cells?
|
1. pluripotent
2. multipotent (comitted to either myeloid or lymphoid lineages) 3. progenitor 4. precursor cells ("blasts") |
|
if the % neutrophils is 50%,
what is the absolute neutrophil count? |
5,000
(.5 x 10,000) 10,000 is normal WBC count |
|
which type of infections are characteristic of agranulocytosis?
|
ulcerating necrotizing infections
(bacterial or fungal) |
|
three morphologic changes seen in neutrophilia?
|
1. Dohle bodies
2. toxic granulation 3. cytoplasmic granules |
|
why are toxic granulations formed?
|
cells are released before they are completely mature
|
|
why are cytoplasmic vacuoles and Dohle bodies seen in neutrophilia?
|
characteristic of reactive changes
|
|
Dr. Raymond guaranteed Q:
very large lymphocytes seen in lymphocytosis of a young female would very likely be? |
Infectious mononucleosis
|
|
three major causes of eosinophilia?
|
1. parasites
2. allergic disorders (MCC) 3. skin disorders |
|
where in the lymph node are B cells found?
|
in the follicles of the cortex
|
|
where in the lymph node are T cells found?
|
paracortex
|
|
what normally passes through the capsule of the lymph node?
|
afferent and efferent lymph
|
|
these 3 disorders are commonly associated with which type of reactive lymph node disorder?
1.prominent germinal centers 2. variation in size and shape of follicles 3. associated with RA, toxoplasmosis, early HIV |
Follicular hyperplasia
|
|
what three clues upon lymph node examination help us to differentiate lymphadenitis from lymphadenomas?
|
non-malignant lymph nodes are:
1. tender 2. enlarged 3. mobile in a malignancy they are nontender and nonmobile |
|
what is the most common cause of sinus histiocytosis thought to be?
|
thought to be an immune response against a tumor (seen alot in response to breast cancer)
|
|
in which type of hyperlasia do T cells undergo transformation to immunoblasts?
|
paracortical lymphoid hyperplasia
|
|
the majority of non-Hodgkins lymphomas (80-85%) are of which origin?
|
B-cell origin
|
|
what is notable about the type of proliferation seen in NHL?
|
monoclonal proliferation
|
|
when in life do most B cell NHLs appear?
|
6th or 7th decade
|
|
which two lymphomas are the only ones common in children?
|
1. Burkitt
2. Large B-cell lymphoma |
|
in NHL:
2/3 present with non-tender nodal enlargement 1/3 present with extranodal involvement. where are these extranodal tissues? |
oropharynx
gut skin brain |
|
what is the difference in prognosis between an indolent and an agressive lymphoma.
|
indolent: slow course, generally incurable
aggressive: rapid progression, may be curable |
|
what are two examples of indolent lymphomas?
|
CLL
follicular lymphoma |
|
what are two examples of aggressive lymphomas?
|
Burkitt
Large B cell |
|
what are the three classifications that WHO uses for lymphomas?
|
1. lymphomas with predominant lymphadenopathy
2. lymphomas with predominant extranodal involvement 3. lymphomas with predominant bone marrow involvement |
|
which type of lymphoma is the most common form of NHL in adults?
|
follicular lymphomas
|
|
describe the morphology/growth pattern seen in follicular lymphoma
|
nodular growth pattern
no capsules |
|
describe the genetic alterations seen in follicular lymphoma
|
(14,18) translocation
result is overexpression of BCL-2 protein BCL-2 is an antagonist of apoptosis |
|
describe the B cell origin seen in follicular lymphoma
|
CD19+
CD20+ CD10+ (positive for B cell markers) CD5- |
|
exactly which loci are translocated in follicular lymphoma?
|
heavy chain (IgH) locus on chromosome 14
BCL-2 locus on chromosome 18 |
|
function of BCL-6?
|
regulates germinal center development
(seen in follicular lymphoma) |
|
in 30-50% of cases, follicular lymphoma transforms to which 2 lymphomas?
|
1. diffuse large cell lymphoma
2. Burkitt-like lymphoma |
|
median survival of follicular lymphoma?
|
7-9 years
(indolent but not curable) |
|
what is the second most common B cell lymphoma?
|
Diffuse Large B-cell lymphoma
|
|
most common age of diffuse B-cell lymphoma?
|
middle age or elderly
(also seen in 5% of childhood lymphomas) |
|
genetics of diffuse B-cell lymphomas show which translocation? (3)
|
BCL6 translocation
(14,18) translocation in 10% mutations in c-myc oncogene |
|
two subtypes of diffuse large cell B-lymphomas?
|
1. immundoeficiency associated large B-cell lymphomas
2. Body cavity large cell lymphoma |
|
how does Diffuse Large B-cell lymphoma present?
|
rapidly enlarging mass at a single nodal or extranodal site
|
|
what are the three types of Burkitt's lymphoma?
|
1. endemic in Africa
2. non-endemic in US 3. aggressive subset in HIV patients |
|
describe the hallmark morphology seen in Burkitts
|
high mitotic index
benign macrophages create (STARRY SKY PATTERN) |
|
describe B cell origin of Burkitts lymphoma
|
idicates origin from germinal centers
CD19+ CD20+ CD10+ BCL-6+ |
|
which translocation is associated with Burkitts?
|
(8,14) translocation
c-MYC oncogene on chr. 8 heavy chain locus on chr. 14 |
|
which virus are the majority of African cases associated with?
|
EBV
|
|
regarding Burkits lymphoma:
describe the presentation in: 1. African (endemic) 2. US |
1. mandible
2. ileocecum, peritoneum |
|
describe the progression of Burkitt's lymphoma
|
very aggressive
highly responsive to chemo most children and young adults cured |
|
what is the other name for Small lymphocytic lymphoma? (SLL)
|
chronic lymphocytic leukemia (CLL)
leukemic form of SLL |
|
how common is CLL?
|
extremely (25%)
|
|
avg. age of CLL/SLL patient?
|
>50 yrs
|
|
describe the cell markers seen in CLL/SLL
|
CD19+
CD20+ also CD23+ CD5+ |
|
significance of CD5+?
|
T cell marker
this is used for diagnosis of CLL/SLL |
|
MC chromosomal abnormality SOMETIMES seen in CLL/SLL?
|
trisomy 12
|
|
median survival of CLL pt?
|
4-6 yrs
|
|
guaranteed Q:
older adult male with pancytopenia, hypercellular bone marrow; and splenomegaly - what is it? |
Hairy Cell Leukemia
|
|
what are hairy cells and where are they found?
|
malignant B cells
ciculate in peripheral blood, bone marrow and spleen |
|
which test, if positive, is a reliable indicator of hairy cell leukemia?
|
TRAP
(tartrate-resistant acid phosphatase) |
|
current treatments for HCL?
|
interferons
chemotherapy (lasting remission and possible cures) |
|
why is a dry tap commonly seen in HCL?
|
reticulin fibrosis of bone marrow
|
|
what type of neoplasm is characterized by expansion of a single clone of Ig secreting cells?
|
plasma cell neoplasm
|
|
what are Bence-Jones proteins?
|
light chains of Igs that are small enough to be excreted in the urine
|
|
what happens to the heavy chains in a plasma cell neoplasm?
|
they circulate in the plasma
|
|
what is the most common plasma cell neoplasm?
|
Multiple myeloma
|
|
what is multiple myeloma characterized by?
|
skeletal involvement at multiple sites
|
|
which molecules actually mediate the bone destruction seen in MM?
|
cytokines
|
|
which two hallmark lab findings are seen in MM?
|
Roleaux formation
anemia |
|
most myelomas are disorders of which Ig?
|
IgG
(then IgA) |
|
why is there hypercalcemia seen in MM?
|
from breakdown of bone in "punched out" bone lesions
|
|
MCC of death in MM pts?
|
recurrent infections
(due to decrease in all other Ig's besides the one elevated) |
|
renal involvement is multifactorial in MM. what are three causes?
|
1. Bence-Jones proteins
2. metastatic calcification (due to hypercalcemia) 3. amyloidosis |
|
median survival of MM?
|
3 yrs
|
|
two treatments for MM?
|
chemotherapy
bone marrow transplant |
|
what is significant about solitary myeloma? (plasmacytoma)
|
most bony lesions eventally progress to MM
|
|
lymphoplasmacytic lymphoms (Waldenstrom's macroglobulinemia) is characterized by plasma cells that secrete?
|
monoclonal IgM
|
|
lymphoplasmacytic lymphoma (Waldenstrom's) is best viewed as a cross between?
|
MM and SLL
|
|
describe the morphology seen in lymphoplasmacytic lymphoma (waldenstroms)
|
Roleaux formation
lymphoplasmacytic lymphocytes |
|
age of presentation of lymphoplasmacytic lymphoma?
|
6th-7th decade
|
|
what are two hallmark problems seen in lymphoplasmacytic lymphoma?
|
1. bleeding (Igs form complexes with clotting factors)
2. hyperviscosity syndrome (due to large size of IgM) |
|
what is the hallmark of monoclonal gammopathy of undetermined significance?
|
dysproteinemia without associated disease
(20% progress to MM, waldentrom's or amyloidosis) |
|
what is the most common form of malignancy in young adults (10-30)?
|
Hodgkin's Lymphoma
|
|
what is the distinctive malignant cell seen in Hodgkin's lymphoma?
|
Reed-Sternberg cell
|
|
origin of R-S cell?
|
germinal center derived B cells
|
|
how do clinical features differ from NHL?
|
most often localized to a group of lymph nodes
(NHL - diffuse) |
|
what are the 5 subtypes of HL?
|
1. nodular sclerosis (MC)
2. mixed cellularity 3. lymphocyte rich 4. lymphocyte depletion 5. lymphocyte predominant |
|
describe how lymphocyte predominant HL presents
|
only type of HL that stains like a B cell lymphoma
CD45+, CD20+ (Bcell markers) CD15-, CD30- (R-S markers) |
|
CD staining in Nodular sclerosing HL?
|
CD15+, CD30+
CD45-, CD20- |
|
which R-S variant is seen in nodular sclerosing
|
lacunar cell
|
|
classic test scenario:
20 yr old female presents to clinician with fatigue cervical, supraclavicular lymph nodes enlarged multiple mediastinal lymph nodes on X-ray, R-S cell |
nodular sclerosing HL
(only variant in which males are not more common than females) |
|
morphology of R-S cell in mixed cellularity HL?
|
classic R-S cell
|
|
mixed cellularity HL is strongly associated with ?
|
EBV
|
|
rarest form of HL?
|
lymphocyte depletion
|
|
which age patient has a better prognosis when presenting with HL?
|
younger = better prognosis
older = more systemic involvement |
|
what is the most prognostic variable of HL?
|
tumor burden (stage)
|
|
problem with long term survivors of HL treated with chemotherapy?
|
increased risk of developing second cancers
|
|
in relation to acute leukemia:
1. what describes it? 2. what is the profile of normal hematopoietic stem cells? |
1. clonal expansion of transformed stem cells and failure of maturation
2. normal cells are suppressed |
|
1. ALL is a malignancy involving?
2. AML is a malignancy involving? |
1. transformation of lymphoid series
2. transformation of the myeloid series |
|
describe the onset of acute leukemia?
|
abrupt onset
|
|
for each of the following symptoms, explain the cause:
1. fatigue 2. fever 3. bleeding 4. bone pain |
1. fatigue is due to anemia
2. fever is due to neutropenia 3. bleeding is due to thrombocytopenia 4. bone pain is due to marrow expansion |
|
what is the defining criteria (as far as lab finding go) for acute leukemia?
|
20% or greater blasts in the blood or bone marrow
|
|
which leukemia accounts for 80% of childhood acute leukemias?
|
ALL
|
|
what age is the peak incidence of ALL?
|
4 yrs
|
|
which sex is more commonly seen in ALL?
|
males
|
|
which type of ALL has a better prognosis: pre-B cell or pre-T cell ALL?
|
pre-B cell ALL has a better prognosis
|
|
which markers are seen in pre-B cell ALL?
|
CD19+
CD10+ sIg- |
|
which markers are seen in pre-T cell ALL?
|
CD2+
CD5+ CD7+ sIg- |
|
precursor T cell ALL closely resembles what lymphoma?
|
lymphoblastic lymphoma
|
|
TdT+ indicates what kind of cell?
|
very immature cell
(could be T or B cell) |
|
what is the characteristic clinical feature of lymphoblastic lymphoma?
|
prominent anterior mediastinal mass in 50-70% of pts.
|
|
is lymphoblastic lymphoma common?
|
yes (40% of all childhood lymphomas)
|
|
clinical situation:
19 yr. old male with huge mediastinal mass impinging on breathing? |
lymphoblastic lymphoma
|
|
what separates lymphoblastic lymphoma from pre-T cell ALL?
|
# of blasts in peripheral blood smear.
(lymphoblastic lymphoma may progress to pre-T cell ALL) |
|
in regards to cytogenetic abnormalities:
1. which one is associated with A GOOD PROGNOSIS? 2. which one is associated with a poorer prognosis? |
1. hyperdiploidy
2. translocations |
|
which translocations are present in ALL? (3)
|
+(9;22)
+(4;11) +(12;21) |
|
prognosis for ALL?
|
90% acheive remission
2/3 considered cured |
|
as far as age goes:
which age is associated with a better prognosis? how about a worse one? |
better prognosis: 2-10 yrs
worse pronosis: <1 yr, >10 yrs |
|
AML affects primarily what age group?
|
adults
|
|
what is the morphology of the bone marrow seen in AML?
|
Auer rods!
|
|
clinical scenario:
red dots on arms (petechiae) kid complains of pain in leg tired 50% blasts in peripheral blood TdT+, CD10+, CD19+ what is the diagnosis? |
precursor B cell leukemia
|
|
what will a myeloperoxidase stain tell us?
|
it will show us cytoplasmic granules in AML
tells us we have a myeloid lineage, not a lymphoid lineage (VERY HELPFUL!) |
|
which type of AML is treated differently and therefore "stands out" from all the others? (the one we need to know about?)
|
M3 -> acute promyelocytic Leukemia
|
|
what is acute promyelocytic leukemia characterized by as far as cell shape goes?
|
characterized by a proliferation of abnormal promyelocytes
|
|
characteristic translocation seen in acute promyelocytic leukemia?
significance? |
+(15;17)
produces RARa-PML fusion protein |
|
what are the abnormal promyelocyte cells seen acute promyelocytic cells called?
|
Faggot cells
(multiple Auer rods) |
|
which stain are the abnormal promyelocytes positive for?
|
myeloperoxidase stain
|
|
what disorder is acute promyelocytic anemia associated with?
|
DIC
|
|
treatment for promyelocytic leukemia?
|
retinoic acid
(induces maturation of promyelocytes) ALSO ADD CHEMOTHERAPY |
|
the following translocation is associated with?
+(9;22) prognosis? |
AML-M1 (also CML)
(this is the Ph chromosome) poor prognosis |
|
the following translocation is associated with?
+(8;21) prognosis? |
AML-M2
more favoable prognosis |
|
the following translocation is associated with?
+(15;17) |
acute promyelocytic anemia (AML-M3)
|
|
the following translocation is associated with?
Inv(16) prognosis? |
subtype of M4 with increased eosinophils
longer median survival time than other types of AML |
|
in contrast to AML: what is it called when the blast count in the bone marrow is less than 20%?
|
myelodysplastic syndrome (MDS)
|
|
MDS typically affects which age group?
|
older individuals
(over age 50-60) |
|
In MDS: what does the peripheral blood and bone marrow show as far as cell count goes?
|
peripheral blood - pancytopenia
bone marrow - hypercellular |
|
what are Pseudo-Pelger-Huet cells?
|
unilobed or bilobed neutrophils
(Harry Potter glasses) |
|
what else in notable about the neutrophils seen in MDS?
|
they are agranular or hypogranular
(vs. hypergranular neurophils - seen in bacterial infx) |
|
refractory anemia (RA) is characterized by?
|
ineffective erythropoiesis
predominately RBC disorder |
|
what characterizes refractory anemia with ringed sideroblasts? (RARS)
|
ringed sideroblasts (abnormal iron accumulation)
|
|
what characterizes refractory cytopenia with multinlineage dysplasia? (RCMD)
|
two or more blood cytopenias and dysplastic changes in two or more major lineages
|
|
Auer rods are indicative of which type of MDS?
|
RAEB (refractory anemia w/ excess blasts)
|
|
what percentage of blasts are seen in RAEB?
|
5-9%
|
|
what would the neutrophils look like in RAEB?
|
harry potter glasses (pseud-Pelger-Huet cell)
hypogranulation |
|
which is the most aggressive of the MDS?
|
RAEB
|
|
what do cytopenias tell us about the prognosis of MDS?
|
more pancytopenia - worse diagnosis
|
|
RAEB effects which cell lineages?
|
ALL THREE
(pancytopenia with trilineage dyspoiesis) |
|
what is the name of the new drug used to treat MDS?
|
azacitidine
|
|
what are the four chronic myeloproliferative disorders?
|
1. CML
2. Polycythemia vera 3. Primary myelofibrosis 4. Essential Thrombocytopenia |
|
what can we do to easily rule out one of the chronic myeloproliferative disorders?
|
look for the Ph chromosome
(rule out CML) |
|
why are all the chronic myeloproliferative disorders associated with splenomegaly?
|
all have extramedullary hematopoiesis
|
|
what is the "spent phase" seen in chronic myeloproliferative disorders?
|
marrow fibrosis
cytopenias |
|
all chronic myeloproliferative disorders can progress to?
|
acute leukemia
|
|
what is the dominant cell line in CML?
|
granulocytic precursors
|
|
where does the Ph chromosome translocation lie?
|
+(9;22)
chr. 9 has ABL gene chr. 22 has BCR gene translocation results in BCR-ABL fusion |
|
function of BCR-ABL fusion gene?
|
directs synthesis of a fusion protein with tyrosine kinase activity
|
|
peak incidence of age seen in CML?
|
30-40 yrs
|
|
speed of onset of CML?
|
slow
initial symptoms are nonspecific |
|
what two things cause the symptoms experienced in CML?
|
anemia
hypermetabolism (fatigue, weakness, weight loss, anorexia) |
|
what is result in the peripheral blood smear that is a tip-off telling us we have CML?
|
elevated basophils
|
|
what would the leukocyte count be in a pt with CML?
|
> 100,000 cells per mm cubed
|
|
what would the bone marrow look like in a CML patient?
|
hypercellular
granulocytic hyperlasia |
|
what characteristic test can be used to distinguish CML from a leukemoid rxn?
|
LAP (leukocyte alkaline phosphatase)
CML - very very low LAP leukemoid - high |
|
what are the 3 clinical phases of CML?
|
1. Chronic
2. Accelerated 3. Blast |
|
characteristics of the chronic phase?
|
relatively asymptomatic
hypercellular bone marrow phase lasts 3-4 yrs |
|
characteristics of the accelerated phase?
|
worsening anemia, thrombocytopenia
progressive myelofibrosis increase in blasts (<20%) |
|
characteristics of the blast crisis phase?
|
20-30% blasts
(50% enter the blast phase immediately following the chronic phase, skipping the accelerated phase) |
|
which drug induces remission in >90% of CML patients?
MOA? |
Gleevec
inhibits BCR-ABL kinase |
|
which cell line dominates in polycythemia vera?
|
erythroid precursors
|
|
avg. age of onset of polycythemia vera?
|
60s
|
|
what is the major clinical problem in p.vera?
|
increased blood volume and viscosity
see: vascular stasis thrombotic tendency hemorrhage |
|
1. blood findings in P. vera?
2. bone marrow findings in P. vera? |
1. increased RBC count, Hgb, Hct.
2. hypercellular, increased erythroid precursors |
|
In P. vera:
1. LAP results? 2. presence of Ph. chromosome? |
1. increased
2. NO (Ph chr. absent) |
|
P. vera patients have an increased risk of?
|
both hemorrhage and thrombosis
-hemorrhage b/c of abnormal platelet function and blood vessel distention |
|
what is the treatment for P. vera?
|
phlebotomy
(decrease chance of thrombosis and hemorrhage) |
|
what about P. vera and iron stores?
|
decreased iron stores
(secondary to chronic bleeding) |
|
primary myelofibrosis involves the formation of abnormal megakaryocytic precursors that release what growth factors?
|
PDGF
TGF-B (mitogenic for fibroblasts) |
|
what is the hallmark of primary myelofibrosis?
|
early progression to marrow fibrosis (similar to "spent phase" but earlier onset)
|
|
in primary myelofibrosis: what happens as marrow fibrosis progresses?
|
get extramedullary hematopoiesis (spleen. liver, lymph nodes)
|
|
what are often the first 2 clinical presentations seen in primary myelofibrosis?
|
anemia
splenomegaly |
|
typical age of onset of primary myelofibrosis?
|
60s or older
|
|
in primary myelofibrosis:
what is seen in the RBC morphology that is associated with fibrosis of the bone marrow? |
teardrop RBCs
|
|
what are leukoerythroblasts?
what do they indicate? |
immature red cells and granulocytic precursors
*not a good finding / indicates problem with bone marrow* |
|
what do the platelets look like in primary myelofibrosis?
|
large and bizarre
|
|
clinical scenario:
70 year old male pancytopenia large spleen dry tap teardrop RBCs |
primary myelofibrosis
|
|
essential thrombocythemia (thrombocytosis) is characterized by?
|
predominant proliferation of megakaryocytes
|
|
two main presenting symptoms of essential thrombocytosis?
|
thrombosis
abnormal bleeding |
|
describe the platelets seen in essential thrombocytosis
|
HIGH platelet counts
abnormally large bone marrow has increased atypical megakaryocytes |
|
is the Ph chromosome present in essential thrombocytosis?
|
NO
|