Adult Leukemia Flashcards
Objectives
Describe commons signs/symptoms of acute leukemia
Define complete response following induction therapy
Identify specific dose-limiting toxicities for common chemotherapy agents used in the treatment of leukemias
Be able to identify clinical factors (hepatic, renal) that require dose-modifications for common chemotherapy agents used in the treatment of leukemias
Differentiate between autologous and allogeneic hematopoietic stem cell (bone marrow transplants) in terms of the source of donated cells
Define induction, consolidation, and maintenance in the context of chemotherapy regimens.
what two cell lines are implicated in the types of leukemias that can present?
Myeloid progenitor cells
Lymphoic cells
What does lymphoid progenitor cells lead to the creation of ?
B and T cells
what do myeloid progenitors lead to?
granulocytes
monocytes
megakaryocytes
erythrocytes
what are the four types of leukemia?
Acute lymphocytic leukemia ALL
acute myelogenous leukemia AML
chronic lymphocytic leukemia CLL
chronic myelogenous leukemia CML
what kinds of general treatment strategies are available for leukemia?
chemontherapy
no surgery
possible radiation
what is the difference between De-Novo vs secondary leukemia?
de novo means that we don’t know the cause and is generally less agressive than secondary
Secondary: we know the cause.
-radiation, chemical, chemotherapy exposure etc.
-generally more aggressive if due to chemotherapy
what is the main pathophysiology of leukemias?
mutations and disruptions of normal bone marrow function or bone marrow failure
what are the signs and symptoms oaf acute leukemias?
anemia: fatigue, weakness, pallor
thrombocytopenia: bleeding, bruising
neutropenia: infections
hyperleukocytosis: compromised circulation
splenamegaly, lympahdenopathy
how do you diagnose leukemia?
perform a blood smear : CBC perform a bone marrow biopsy cytogenetics flow cytometry lumbar puncture
what is the purpose of the biopsy?
to tell you what kind of leukemia the patient has
what is the purpose of the cytogentietcs and flow cytometry?
analyzing the chromosomes and studying the genetic makeup (mutations) of each of the cancers. This will allow you to tailor therapy and tell you about prognosis
what is the purpose of lumbar puncture?
to see if any of the cancer in the CNS hiding. generally harder to treat if there are some cells there, and should be more agressive with therapy.
in the CBC, what are they looking for that tells you it is leukemia?
blast looking cells and increasing WBC
why dont parents get used for HLA matching for bone marrow transplants?
because they cannot be 100% matches since they gave 50% of their genes to their children
which patients are candidates of standard-dose chemotherapy?
patients iwth favorable prognosiis
which patietns are candidates for radiation therpay?
for when the disease site is hard to be reached by chemotherapy
what is high dose chemotherapy wit h autologous stem cell rescue?
Auto BMT.
the patient will be given high doses of chemo. They then remove progenitor cells from the bone marrow. Then they will put back the bone marrow progenitor cells of the patient as a rescue.
what is an allogeneic bone marrow translplant or stem cell transplant?
IT is where they shut down the patients bone marrow but instead use someone else’s healthy donor cells from the bone marrow
what dues ALL stand for?
acute lymphocytic leukemia
what is the standard treatment plan of chemotherapy for ALL?
- induction: induce remission
- consolidation: cytoreduce remaining leukemic cells
- CNS prophylaxis: CNS can be sanctuary site
- Maintenance of remission
what is the definition of complete remission?
no leukemic cell
normall cell counts
no estramedullary disease
less than 5% blasts in the marrow
why use comibination chemo therapy?
different MOA
Cell cycle specificity
lower doses of each drug
lower risk of drug resistance
What is linker’s regimen induction for ALL?
it is induction therapy that invovles givving methotrexate IT at time of diagnostic lumbar puncture, daunorubicin IV, vincrisitine IV, high dose dexamethasone (18mg/m2), asparaginase. Patients need to stay in the hospital for 1 month. After that, they need 7-10 day of break then they start consolidation
what is involved in consolidation therapy 1B?
etoposide IV x 4 days and high dose cytarabine IV x 4 days. Then patient is in the hospital for a month. Given 7- 10 days break then starts 1 c.
what is involved in consolidation therpyp (linker’s) 1C ?
pt given high dose methotrexate iv infusion, leuocovorin IV rescue, daily po mercaptopurine. Patient is given a total of 2 methotrexated courses separated by 2 weeks. Total IC duration is one month
what is the consolidation schedule?
1A, 1B, 1C, IIA, IIB, IIC (4 courses of MTX instead of 2= 2 months)
what is the maintenance schedule for linker’s regimen/
daily oral mercaptopurine and weekly oral methotrexate after the completion of all IV chemotherapy (total chemo takes ~2 years)
what is the CNS prophylaxis dosing?
methotrhexated 12mg IT q week x 6 doses. first dose can be given at beginning of induciton therpay
what is the CNS Treatement dosing ?
methotrexated 12mt IT q week x 10 doseis with cranial radiation after consolidation IB
what are the general side effects of agents that mess with DNA or RNA synthesis?
myelosupression, mucositis, alopecia
what is the mechanism of aciton of the anthrayclines?
inhibition of topoisomerase II
what are the class tocxicities and specific tosxicities of daunorubicin?
Class: myelosuppression, mucositis, alopecia
cardiomyopathy
Specific: vesicant: prefer centrla line
red urine, adjust dose for hepatic impairment
what labs are required before starting the patient on daunorubicin?
ECHO
hepatic function
what should you do if the patient sees red urine?
there is nothing to do except tell the patient to expect it and that it is not harmful.
what if a central line cathether is not available?
nurses can pus medication peripherally in patient but should do it slowly and w/ awarness of damage to tissue
what is the mechanism of action of the vincrisitine?
vinca alkaloids inhibit microtubules in the M phase.
what are the side effects to expect with vincrisitne?
nuerotoxicity ( peripheral neuropathy)
ileus, constipation
vesicant
which route should your never give vincristine through?
Intrathecally: FATAL
renal or hepatic adjustment for vincristine?
hepatic adjustment
what is the equivalence of dexamethasone and prednisone?
4mg dex = 30mg prednisone
what are the immediate side effects of dexamethasone?
depression/psychosis insomnia GI bleed hyperglycemia adrenal supression opportunistic infections
what is the mechanism of aciton of asparaginase?
deprives tumor cells of asparagine for protein synthesis
what are the side effects of aspargianse?
hypersensitivty rxn : watch x 2 hours hepatoxicity coagulaopathy : depleting clottign factors pancreatic dysfxn: pancreatitis hyperglycemia
what labs should you monitor for aspariginase?
LFTs
INR
blodo sugar
what is the MOA of etoposide?
topoisomerase II inhibition
main side effects for etoposide?
classs: muchositis, alopecial, meylousuppression
hypotension, fever, metabolic acidosis (only with high dose which is not used for ALL)
can be irritatn
renal or hepatic adjustment?
renal if < 50ml/min dec dose by 25%
what is the brand name of cytarabine?
Ara-C
what is the MOA of cytarabine?
pyrimidine analogue inhibits DNA synthesis
main side effects of cytarabine
myelosuppression fever , rash conjunctivitis if high dose Ara-C. skin toxicity CNS toxicity at >200mg/m2/day high dose
what do you do about the conjunctivitis caused by high dose Ara C ?
use steroid eye drops: fluromethalone or dexamehtasone 0.1% 1-2 drops both eyes till 48 hrs after completion of Ara-C
what to do about skin toxicity with Ara-C
showers BID otherwise pt will get a chemical burn
what is the MOA of MTX?
dihydrofolate reductase inhbitor
side effects of MTX?
myelosupression, mucositis dose related
can cause renal failure
CNS effects > wit hIT MTX
renal or hepatic dose adjustment for MTX?
renal, can cause renal failure
when is leucovorin rescue for MTX mandatory?
when using high-dose MTX > 200mg/m2
what is mandatory for high dose MTX?
leucovoin rescue
hydration and alkalization of urine
what isth e MOA of 6-MP
antimetabolite: purine analoge
what are the SEs with 6MP ?
myelosuppression: leukopenia is dose limiting toxicity
cholestatis (inc in LFTs)
renal or hepatic adjustement in 6MP
hepatic
what is the supportive care for ALL?
tumor lysis prophylaxis w/ allopurinol + agressive hydration or rasburicase
-PCP prophylaxi
-growth factors and antibiotics for febrile neutropenia
antiemetics during chemo
-transfusion ofr anemia, thrombocytopenia
what is acute myeloid leukemia?
leukemia of the granulocytes, monocytes, erythrocytes, and platelets
what is the UCSF method to treating AML?
induction therapy
consolidation and autologous stem cell collection
high dose chemo w/ atologous stem cell rescue
what is induction therpy for AML? UCSF
high does cytarabine x 6 days
daunorubicin x 3 days
what is AML consolidation?
high dose cytarabine x 4 days
etoposide continuous infusio nx 4 days (not high dose)
high dose G-CSF
what is given for the autologous stem cell transplant?
busulfan x 4 days high dose etoposided of the fift day rest x 2 days autologsous stem cell infusion on seventh day palifarin q x 3 pre-chemo
What is the MOA of busulfan?
it is an alkylating agent
what are the SE s of busulfan?
myelosuppression, mucositis
skin pigmentation
veno occlusive disease
what is the purpose of autologous bone marrow transplant?
to rescue the lethal side effect of high-dose
what agent is used to treat AML-M3 ?
tretinoin =ATRA
what is the MOA of tretinoin?
it binds to the chimeric gene product of a translocation that has occurred in the cancer cell on chormosome 15. this causes the leukemic clone to mature and undergo apoptosis
what is ATRA Syndrome?
= dirfferentiation syndrome -SOB, -pleural effusions fever peripheral edema