Malignant Hematology (blood cancer) EXAM 3 Flashcards
What are the different types of Leukemia in terms of their origin?
Myelogenous (too much myeloblasts, platelets, RBC)
acute: AML
chronic: CML
Lymphocytic (too many lymphocytes)
acute: ALL
chronic: CLL
Lymphomas stems from which tissues?
Lymph nodes
Hodgkin’s lymphoma - good cure rates
Non-Hodgkin’s: variety in cancer cells
-B-lymphocytic or T-lymphocytic origin
Myeloma is cancer of which cells?
Plasma cells
Surgery might be considered in some types of myeloma. T/F
False.
Surgery is never an option, since it is cancer of the blood
ALL and AML are rapidly growing cancers. They have the highest risk of what?
-Highest risk of neutropenic fever
-Highest risk of tumor lysis syndrome (TLS)
What is the dose of Rasburicase in adults and children?
adults: 3 mg or 6 mg usually sufficient
children: 0.15 to 0.2 mg/kg IV daily for up to 5 days
Acute Leukemia Patient Presentation
-Fatigue, not feeling well, malaise, fever, pallor, weight loss, bone pa
-Anemia (fatigue, pallor)
-Thrombocytopenia (Petichiae (spots of bleeding under the skin), epistaxis, bleeding)
-Leukocytosis or leukopenia (depending on the time of diagnosis, WBC goes low than high)
-Infection/neutropenia (more in AML)
What are the signs of Tumor Lysis Syndrome?
REMINDER
-Hyperkalemia -> Arrhythmia
-Hyperphosphatemia -> Arrhythmia
-Hypocalcemia -> precipitation and AKI
-Hyperuricemia -> AKI
What is the concept of ALL treatment?
OBJECTIVE !!
- Induction chemotherapy (kill all cells (healthy and cancer) to achieve remission (no detectable cancer cells)
- Consolidation: more intense therapy bc the cells that have survived are more resistant
->then small cycles to give the body time to recover - delayed intensification, even more intense therapy
- Intrathecal chemo to kill ALL in the CNS
- Maintenance for 2.5 years with low dose of Mtx (weekly) and 6-MP daily, steroids monthly (kills lymphoma cells)
Which supportive or prophylactic drugs would you use during ALL cancer treatment?
!!!
-prevent TLS during induction
-prophylactic antimicrobials
Bactrim, fungus, PJP
What is the drug of choice to manage TLS?
REMINDER
Allopurinol 300 mg with hydration (NS)
-NS + Rasburicase for high-risk patients for TLS (WBC of 50k to 100k) or if they have Burkitt lymphoma
What are the late effects of ALL treatments?
secondary leukemia
-chronic health issues (higher rates of HF from anthracyclines)
-cognitive issues
Which drugs are used for ALL?
Combination of..
-Daunorubicin
-Cyclophosphamide
-Vincristine (no myelosuppression)
-Prednisone and dexamethasone (kills lymphocytes)
-Pegaspargase or Calaspargase (L-asparginase)
-Intrathecal chemo for all (cancer in the CNS): only
Mtx or Cytarabine
Corticosteroids kill which cells. They don’t have what type of side effect compared to anticancer drugs…
kill lymphocytes
no bone marrow suppression
What is the function of Pegaspargase or Calaspargase (L-asparaginase)?
hydrolysis of asparagine
cancer cells cant create asparagine by themselves, they get it from the bloodstream
by reducing asparagine from the bloodstream, cancer dies (healthy cells can produce it by themselves)
What are the unique toxicities of L-Asparaginase?
Hypersensitivity: fever, arthralgia, hypotension, anaphylaxis, lysis of asparagine creates ammonia -> sedation
loss of protein:
-Coagulopathies: bleeding and clots (depending on which protein is depleted)
-pancreatitis
-hepatotoxicity (especially in adults) due to glutamine deficiency
Counseling points for 6-MP
REMINDER
-Thiopurine methyltransferase (TPMT) & NUDT gene testing -> dose reduction
-avoid milk (contains Xanthine oxidase - metabolizes 6-MP before absorption)
(allopurinol may decrease 6-MP-induced hepatotoxicity)
What are the differences in treatment outcomes for acute leukemia by age?
-children tolerate chemotherapy better than adults
-cancer is more diverse and complex in adults, so harder to treat
AML: often in adults
ALL: often in kids
Acute Promyelocytic Leukemia (APL) results from which mutation?
translocation of chromosomes 15 and 17 → fusion of PML:RARA
PML: promyelocytic leukemia gene
RARA: retinoic acid receptor alpha gen
-prevents cell differentiation
Which drugs are used to treat APL by stimulating differentiation?
!!!
-All-trans-retinoic acid (ATRA) = tretinoin -> targets RAR and
causes differentiation of APL cells
-Arsenic trioxide -> targets RAR and causes differentiation and apoptosis of APL cells
What is the dose of All-trans-retinoic acid (ATRA) = tretinoin?
45 mg/m2/day PO in 2 divided doses
Which side effects are associated with ATRA (tretinoin)?
!!!
-Retinoic acid/differentiation syndrome
it causes cell differentiation of APL -> so patients have an increased amount of mature immune cells
-dyspnea
-pulmonary infiltrates
-respiratory distress
-wt gain, edema
-headache (80%)
treat with dexamethasone 10 mg IV Q12
What are the side effects of Arsenic trioxide?
!!!
-can cause retinoic acid (aka differentiation) syndrome
-QT prolongation BBW - need baseline EKG !!!
What should be Qtc, potassium and Magnesium before starting Arsenic trioxide?
QTc: <450 or 460 msec
K: > 4.0
Mag: > 2.0
if not at goal it increases the risk of Torsade
What is the treatment concept for AML?
OBJECTIVE !!!
- Remission Induction Chemo (kill healthy and cancer cells) with Anthracycline + cytarabine (Ara-C)
- Consodilation Chemo (more intense)
with High-dose Ara-C x 3-5 cycles - Cure or Stem cell transplant
no 2.5 years of maintenance phase like in ALL
-watch out for TLS and neutropenic ADE
What are the toxicities of a high dose of Ara-C (cytarabine)?
Cerebellar dysfunction: requires monitoring
chemical conjunctivitis -> premed steroid
Which premed is required for high dose Ara-C?
!!!
Corticosteroid eye drops until 48 hours after chemo
Which drugs are used to treat AML in elderly patients? Since they can’t tolerate Anthracyclines due to HF and thrombocytopenia?
Hypomethylating agents (inhibit methyltransferase)
-Azacitidine
-Decitabine
ADE: myelosuppression
Veneteoclax (BCL2 inhibitor)
How do cancer cells stop apoptosis? Hallmark of cancer
REMINDER
upregulation of BCL2
What is the MOA of Venetoclax?
BCL2 inhibitor that prevents tumor cells from evading apoptosis
What are the side effects associated with Venetoclax?
-Potentially severe myelosuppression
-it is a CYP3A4 substrate -> DDI with CYP3A4 inhibitors (esp antifungals)
What are the Hypomethylating agents, and what is the MOA?
-Azacitidine
-Decitabine
MOA: inhibit DNA and/or RNA methyltransferase -> re-expression of silenced genes (tumor suppressor genes)
Which of the following is the most appropriate plan to prevent tumor lysis syndrome?
NS + allopurinol
NS + rasburicase (your response)
NS w/ 50 mEq/L NaBicarbonate + allopurinol
NS w/ 100 mEq/L NaBicarbonate + rasburicase
NS + allopurinol (allopurinol may be started earlier)
if they are at high risk for TLS (WBC of 50k-100k or Burkitt lymphoma)
(no benefit in using NaBicarbonate, it can actually cause crystallization from uric acid precursor (accumulated due to allopurinol))
What is the brand name of Rituximab?
Rituxan
anti-CD20
-ADE: infusion reaction !!!, BP fluctuations
-pretreat with Tylenol, diphenhydramine
-hep B reactivation - pre-screening !!!
2 Types of Lymphomas
B Lymphomas (mostly)
T Lymphomas
How does a patient with Lymphoma present?
!!!
-Lymphadenopathy: swollen lymph nodes
-B symptoms !!!
fever
night sweats
weight loss
Which type of Lymphoma is known to be very aggressive?
Burtkitt’s lymphoma (curable with chemo alone)
Which type of Lymphoma is incurable?
Follicular lymphoma (indolent, slow-growing)
-but they live long with the disease
Which premed is necessary for Burtkitt’s lymphoma due to its aggressive nature and causing TLS?
rasburicase for prophylaxis
Which type of Lymphoma is known to be indolent?
Follicular lymphoma (incurable)
-treat with CHOP and Rituximab
What is the treatment approach for Follicular lymphoma?
-watch and wait
-Radiation
-Chemo: R-CHOP, R-Bendamustine
-Rituximab
-Radioimmunotherapy
What does R-CHOP stand for?
-Rituximab (hep b reactivation, it reduces B-cells and antibody production so a flu shot might not work as well)
-Cyclophosphamide -> hemorrhagic cystatis - fluids
-Doxorubicin (hydroxy daunorubicin) -> look at the cycle to determine the risk of HF (reduction in LVEF)
-Vincristine (Oncovin) -> peripheral neuropathy
-Prednisone -> worsen diabetes if they have T2DM
R-CHOP is used for B-lymphomas
CHOP is used for T-lymphomas
Which drugs are in R-EPOCH? How are they different?
same as R-CHOP + Etoposide
R-EPOCH is used for high-risk DLBCL Lymphoma
-R-EPOCH has less cardiotoxicity bc Doxorubicin is given at a lower dose and at days 1 to 4 (96h infusion)
-Etoposide and Vincristine are given over 96h so it hit the cancer more often in the S-cycle
-may increase the dose of R-EPOCH if no neutropenia
What are the side effects associated with Rituximab?
REMINDER
-Infusion reaction - start slow
-Hep B reactivation - check Hep B serum
!!!
Brentuximab vedotin binds to which cells?
binds to CD-30 (found primarily on Hodgkins lymphoma cells)
Polatozumab vedotin binds to which cells?
binds to CD-79
part of the B-cell receptor -> only on B-cells
Vedotin is conjugated with Brentuximab and Polatozumab, what drug is vedotin, and what side effect might we see from it?
vedotin is a microtubule inhibitor
we see some peripheral neuropathy
How does Blinatumomab work in ALL?
one chain binds to a T-cell effector cell (CD-3), the other chain binds to cancer CD-19 B-cells
Blinatumomab the T-cell close to the cancer B-cell and causes the T-cell to kill the cancer cell
used for ALL, eliminates all B-cells in the body
How do CAR-T drugs work in ALL?
reprogramming of T-cells (with viruses) to target CD-19 cells
Side effects of CAR-T
-Cytokine release syndrome (some require tocilizumab or siltuximab treatment)
-Neurotoxicity
-B-cell aplasia (may need lifelong immunoglobulin (IVIG) infusion)
Know the side effects that we expect from Hodgkin’s therapy?
Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
Doxorubicin -> cardiotoxic, red urine/tears, vesicant
Bleomycin -> pulmonary fibrosis
Vinblastine -> myelosuppression
Dacarbazine -> emetogenic (vomiting)
What is the drug class of choice for Chronic Myeloid Leukemia (CML)?
!!!
Tyrosine Kinase inhibitor
-inib
Imatinib -> blocks ATP pocket
1 mutation -> 1 drug for life
Which mutation is required for CML?
!!!
1 single mutation -> 1 drug for life
-translocation of ABL from Chromosome 9 to Chromosome 22
fusion protein BCR-ABL
When is a patient considered to be in treatment-free remission?
CML
-MR4 (major response of 4log reduction) for 2+ years
-adherence is key !!! (make sure their insurance covers them, they have a prescription and enough refills)
Side effects of TKIs for CML
very diverse because blocks multiple tyrosine kinases
-Nilotinib: QT prolongation
-Dasatinib: Pleural effusion, DDI with PPIs
What is the first-line treatment for CLL?
-CD-20 agent + BTK inhibitor
-FCR (fludarabine, cyclophosphamide, rituximab)
-BR (bendamustine, rituximab)
may need TLS prophylaxis
CLL is incurable, but indolent
Why do patients with a deletion on chromosome 17 do poorly with CLL?
FYI
becasue the tp53 gene is on there
What is the role of Bruton’s tyrosine kinase in B-cells? How do BTK inhibitors work?
mostly found in B-cells
-BTK has to be phosphorylated to achieve cell proliferation
-if BTK is blocked -> no B-cell proliferation
Name a Bruton’s tyrosine kinase inhibitor.
-bru in the drug name
Ibrutinib
acalabrutinib
zanubrutinib
pirtobrutinib
What is the unique toxicity of Ibrutinib?
!!!
-Bleeding, easy bruising (Impaired vWF function), more severe if on ASA or anticoagulant, hold for 3-7 days before surgery!
-Htn, a-fib (especially the elderly)
-diarrhea (50%, tolerance develops)
-cytopenia
-infections (bc normal B-cells are affected too)
Which Brutons TKIs have less cardiac side effects?
newer gens: but less studied, so ibrutinib is still used often
acalabrutinib
zanubrutinib
pirtobrutinib
Multiple myeloma is a cancer of which type of cells?
Plasma cells
What are the symptoms of multiple myeloma?
CRAB(i)
Ca2+ elevation → hypercalcemia (resorption into the bloodstream)
Renal dysfunction/failure: nonfunctional light chains clot with kidney cells
Anemia: cancer plasma cells invade the bone marrow and impair RBC production
Bone fractures (lytic lesions)
we also see infection, bc the production of normal antibodies is impaired
Which tool is used to diagnose or assess the treatment progress of Multiple myeloma?
Gel electrophoresis
-M protein spike (produced by cancer cells)
in healthy patients, we don’t see the spike bc usually different plasma cells produce different antibodies
Which drug targets proteosomes in myeloma cells?
proteasome inhibitors
Bortezomib (SQ) - first line
carfilzomib (IV)
ixazomib (PO)
How do proteasome inhibitors work? Why do proteasome inhibitors don’t cause much damage to healthy cells?
-Proteosomes degrade misfolded proteins (antibodies)
-blocking the Proteosome will lead to build up of misfolded protein which causes cell death
-healthy cells don’t produce as much protein, so there is no build-up of proteins
What are the toxicities of Proteasome inhibitors?
OBJECTIVE !!!
-mild thrombocytopenia (bc we don’t actually block the bone marrow activity)
-peripheral neuropathy (less with SC) !!!!
-HSV/VZV reactivation !!!
Patients on Bortezomib (protease inhibitor) also need which drug for prophylaxis?
OBJECTIVE !!!
Acyclovir or Valacyclovir
antiviral prophylaxis to prevent HSV/VZV reactivation
Which side effect do we see with Thalidomide (IMiD) due to its angiogenesis inhibition (similar to VGEF drugs)?
OBJECTIVE !!!
-higher risk for blood clots (VTE) !!!
other side effects:
-increased IL-2 production by T-cells
-decreased TNF production by monocytes
-increased destruction (via proteasome) of IZK1 & IZKF3
What are the 3 Immunomodulatory drugs (IMiDs)?
-thalidomide (not often used in the U.S.)
-lenalidomide !! (often used)
-pomalidomide
What are the side effects of lenalidomide?
OBJECTIVE !!!
-VTE !!!
-peripheral neuropathy
-myelosuppression
-somnolence
-rash
rare: secondary malignancies
Why do patients and physicians need to be enrolled in a REMS program for IMiDs?
OBJECTIVE !!!
Because of the risk of birth defects
-only dispensed for 28 days for each prescription
-counsel patients to avoid donating sperm, or blood, and not get anyone pregnant
Which drug should be given with IMiDs?
OBJECTIVE !!!
Aspirin 81 mg daily
for some patients: full-dose anticoagulation
to prevent VTE
Which protein on the surface of myeloma cells is targeted by Daratumumab? What is the MOA?
CD-38 on myeloma cells
-activation of macrophages, NK cells that recognize Daratumumab
-complement activation
-stimulates apoptosis when bound to the cancer cells
works similarly to Rituximab in R-CHOP for lymphoma which binds to CD-20
Which side effect do we see when administering Daratumumab?
!!!
infusion reaction:
premeds: corticosteroid, Tylenol, diphenhydramine
SC daratumumab/hyaluronidase (lower risk for infusion reaction due to slow release into the blood from SC)
-it will disrupt blood typing (must type blood and screen for RBC transfusion before starting daratumumab) -> some patients might need blood transfusion
Which drugs might be used for bone metastases caused by multiple myeloma?
Bisphosphonates
-Zoledronic acid
-Denosumab
Which lab values should be checked to check for a dose adjustment for an AC Anthracycline-Cyclophosphomide order?
Cases
dose adjustment for Doxorubicin
Renal: SCr
Liver: bilirubin
is the ANC high enough (often it has to be 1500)
is the number of platelets high enough (often needs to be at least 100)
What is a common DDI of Tamoxifen?
DDI with CYP2D6 inhibitors -> decreases tamoxifen
fluoxetine
paroxetine -> change to citalopram (Celexa)
bupropion
Which CDK 4/6 inhibitor should be avoided with citalopram?
Ribociclib
bc it causes QTc prolongation, as well as citalopram
palbociclib has more myelosuppression
abemaciclib has more abdominal pain and cramping
How would mild or severe hypercalcemia be managed?
- need corrected Ca if albumin is low
if mild: fluid intake; if symptomatic IV fluids + loops
if severe:
start with IV fluids -> give bisphosphonate zoledronic acid: 4 mg IV over 15 minutes
pamidronate: 30-90 mg IV over 2h
Create a long-acting pain medication. They are taking Lortab 10/325 q3h.
10 mg Hydrocodone to morphine
8x a day -> 80 mg hydrocodone
convert to morphine: 1:1
use 30 mg MS Contin q8h 30 mg q8h (90 mg)
