Term
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Definition
normal hematopoiesis:
pluripotent stem cell
lymphoid lineage: B and T lymphocytes
myeloid lineage: erythrocytes, platelets, monocytes, basophils, eosinophils, and neutrophils
leukemia: cells do not differentiate past a certain stage and proliferate uncontrollably |
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Term
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Definition
leukemia = unregulated proliferation of blood forming cells in the bone marrow
acute leukemia:
acute lymphocytic leukemia (ALL)
acute myelogenous leukemia (AML) aka acute non-lymphocytic leukemia (ANLL)
chronic leukemia:
chronic lymphocytic leukemia (CLL)
chronic myelogenous leukemia (CML) |
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Term
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Definition
median age of diagnosis:
ALL = 10 years
AML = 65 years
CLL = 6gh decade
CML = 4th-6th decade
gender presentation:
all types with male predominance |
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Term
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Definition
peripheral blood smear
bone marrow biopsy and aspiration:
normal marrow < 5% blasts
acute leukemia > 20% blasts
cytochemical stains
immunophenotyping
cytogenetic analysis |
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Term
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Definition
proliferation of CD5 positive B CELLS (important b/c can use RITUXIMAB)
median age of diagnosis = 72 years
more common in men (2:1) |
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Term
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Definition
diagnosis usually made incidentally
generally considered an indolent disease with no curative potential
no etiologic factors identified
first degree relatives have increased risk
20-30% of cases happen in people < 55 years old |
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Term
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Definition
myelosuppression
lymphocytosis
lymphadenopathy
splenomegaly
hepatomegaly
weight loos |
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Term
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Definition
several features indicate poor prognosis:
ZAP-70 (tyrosine kinase)
deletion 11q
deletion 17p |
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Term
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Definition
decision to treat based on:
age at diagnosis
symptoms
stage
presence of complications (ie infections)
cytogenetics (presence of ZAP-70, deletion 11q or 17p)
worse prognosis, considered more aggressive, should consider treatment even in early stage (I/II) disease
stage III and IV there will be symptoms |
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Term
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Definition
observation
early stage (stage 0), asymptomatic patients
no difference in overall survival
FCR: fludarabine, cyclophosphamide, rituximab |
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Term
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Definition
STAGE 0:
observation
STAGE I/II:
questionable need for treatment, has not been shown to improve survival
patients with ZAP-70 mutation should be treated (same as stage III/IV patients)
observation?
STAGE III/IV:
treatment prolongs survival (median survival 2 years without, 4 years with)
chemotherapy:
FCR (fludarabine, cyclophosphamide, rituximab) |
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Term
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Definition
no salvage regimen produces durable remission
single agent alkylating agent
combination chemotherapy?
ofatumumab
alemtuzumab |
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Term
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Definition
single agent alkylating agent
bendamustine
chlorambucil +/- prednisone
MABs:
ofatumumab
alemtuzumab |
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Term
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Definition
has not been shown to CURE patients
have produced prolonged disease free survival
treatment of future for CLL? |
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Term
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Definition
caused by Philadelphia chromosome
~15-20% of leukemias
median age of diagnosis = 66 |
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Term
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Definition
Philadelphia chromosome:
9,22 translocation
Bcr-abl is an active tyrosine kinase (removes the control of cell division) |
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Term
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Definition
splenomegaly
early satiety
fatigue
anorexia/weight loss
pallor
sternal tenderness
abdominal discomfort
decreased exercise tolerance
night sweats
heat intolerance
gouty arthritis
priapism
tinnitus
LUQ pain secondary to splenic infarction
LEUKOCYTOSIS |
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Term
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Definition
splenomegaly
early satiety
fatigue
anorexia/weight loss
pallor
sternal tenderness
abdominal discomfort
decreased exercise tolerance
night sweats
heat intolerance
gouty arthritis
priapism
tinnitus
LUQ pain secondary to splenic infarction
LEUKOCYTOSIS |
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Term
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Definition
hematologic remission:
measured by CBC
normaliation of blood counts and spleen size
cytogenetic remission:
measured on BM biopsy
complete cytogenetic remission = elimination of Philadelphia chromosome from BM
major cytogenetic response = < 35% Ph |
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Term
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Definition
short course oral chemotherapy to decrease counts
initiate tyrosine kinase inhibitor
consider stem cell transplant with TK inhibitor failure
interferon for TK failures that can't get transplant |
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Term
| CML treatment - oral chemo |
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Definition
busulfan OR hydroxyurea
palliation for chronic phase (decrease WBC)
no effect on cytogenetic response or disease progression
hydroxyurea shown to improve survival compared to busulfan
combination chemotherapy: no improvement over single agent chemotherapy |
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Term
| CML treatment - TK inhibitors |
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Definition
imatinib is the drug of choice based on experience with the drug
dasatinib and nilotinib have both been shown to be effective in imatinib failures
both drugs are 2x as good as imatinib in eliminating any evidence of bcr-abl (major molecular response) however data is only short term
both agents FDA indicated in 1st line and in relapse
imatinib: specific bcr-abl tyrosine kinase inhibitor
most "events" happen within first 3 years of treatment
biological agent
ADRs - FLUID RETENTION, N/V, diarrhea, muscle cramps, rash, myelosuppression, hepatotoxicity |
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Term
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Definition
T315i mutation is present in > 50% of imatinib failures
mutation also associated with nilotinib and dasatinib resistance
transplant is best treatment course in this population |
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Term
| CML treatment - interferon |
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Definition
interferon alpha
MOA: affect proliferation, adhesion, and apoptosis of malignant cells
single agent: 80% HR and 40% MCR
combination:
cytarabine - increased cytogenetic response |
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Term
| CML treatment - transplant |
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Definition
only option for a cure
often limited due to patient age
50-70% long term disease free survival
early mortality up to 50% in transplants |
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Term
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Definition
hydroxyurea to lower WBC count acutely
imatinib
if imatinib relapse in young patient with sibling match, or any patient with T315i mutation -> stem cell transplant
imatinib relapse in elderly patients, or those without match -> dasatanib/nilotinib
last line = interferon +/- cytarabine |
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