Leukemia Flashcards
Signs and Sx of Leukemia
Anemia (fatigue, SOB)
Thrombocytopenia (bleed risk)
Neutropenia (ANC < 500, infection risk)
Tumor Lysis Syndrome
CNS involvement rare (somnolence, headaches, confusion)
Hyperleukocytosis definition
Elevated WBC
- >/= 100,00
- oncologic emergency
- hyperviscosity syndrome: blood sludging
- Sx: stupor, SOB, vision changes
- can lead to stroke, respiratory failure, cardiac ischemia, renal failure, retinal hemorrhage
Hyperleukocytosis management
Hydroxyurea
- used for count control
- used until clinically stable and ready for induction therapy
Leukopheresis
Hydroxyurea
Indication: Hyperleukocytosis
Dosing: physician/patient specific
ADE:
- N/V/D
- tumor lysis syndrome
- long term toxicities (cutaneous vasculitic ulcerations, mucositis, alopecia, hyperpigmentation
FMS-like-tyrosine kinase (FLT3) mutations
Internal Tandem Duplication (ITD)
Tyrosine Kinase Domain (TKD)
promotes proliferation and blocks differentiation
worse prognosis (both are bad ITD is worse than TKD tho)
Isocitrate dehydrogenase (IDH)
targetable mutation in AML
Criteria for high-intensity chemotherapy
- most pts < 60
- pts > 60 without significant comorbidities or end organ dysfunction
- patients with aggressive disease (hyperleukocytosis, TLS at presentation)
- pts who are candidates for allogenic stem cell transplant
7+3 Induction Chemo
7 days of cytarabine continuous infusion
3 days of anthracycline bolus
- daunorubicin OR
- idarubicin
ADE days 1-7:
- N/V, GI, fatigue
ADE days 8-24:
- fatigue, fever/infection, high RBC and platelet transfusion requirement
Additional Induction Regimens (AML)
Midostaurin
- for FLT3 + pts
Gemtuzumab Ozogamicin
- for favorable/intermediate cytogenetics
Liposomal Daunorubicin + Cytarabine
- for secondary (treatment induced) AML
Response criteria in AML
day 14 bone marrow testing:
- < 5-10% blasts
day 28 bone marrow testing for complete remission:
- <5% blasts AND
- ANC > 1000 AND
- Platelets > 100,000
AML Post-Remission Therapy
Only for those who received intensive chemo
High dose Cytarabine (HiDAC)
- gold standard
- can add midostaurin for FLT3+
- if GO was given during induction it can be added here as well (days 1&2 only)
Liposomal daunorubicin + cytarabine
- if given during induction
Low intensity chemo options
Azacytidine + Venetoclax
Low dose Cytarabine (LDAC) + Venetoclax
Ivosidenib + Venetoclax
- only in IDH1
LDAC + Glasdegib
Venetoclax DDI dose adjustments (Azacitidine backbone)
posaconazole / voriconazole: 100mg Venetoclax QD
isavuconazole, diltiazem, verapamil, amiodarone, carvedilol: 200 mg Venetoclax QD
Venetoclax DDI dose adjustments (LDAC backbone)
posaconazole / voriconazole: 150 mg Venetoclax QD
Isavuconazole, diltiazem, verapamil, amiodarone, carvedilol: 300 mg Venetoclax QD
AML targeted therapy pearls
Midostaurin
- FDA approved for new FLT3+ AML
- not FDA approved for relapsed/refractory
Gilteritinib
- FDA approved for relapsed/refractory FLT3+ AML
Ivosidenib
- FDA approved for new and relapsed/refractory IDH1+ AML
Enasidenib
- FDA approved for relapsed/refractory IDH2+ AML
Supportive Care AML:
Transfusions
RBC transfusion if Hgb < 8
Platelet transfusion if platelets < 10,000
Supportive Care AML
Infection prophylaxis (HSV/VZV)
Acyclovir
Supportive Care AML
Infection prophylaxis (antibacterial)
Levofloxacin
- or ciprofloxacin
if allergic to fluoroquinolones:
Augmentin or 3rd gen Cephalosporin
Supportive Care AML
Infection prophylaxis (Fungal & Mold)
Posaconazole***
voriconazole (does not cover mold)
Tumor Lysis Syndrome
Oncologic emergency: rapid tumor breakdown following chemo -> release of potassium, phosphorus, and uric acid
presentation:
- hyperuricemia
- hyperphosphatemia
- hyperkalemia
- N/V/D
- edema
- acute renal failure
- hematuria, uremia
- CHF, dysrhythmias
- syncope
- seizure
- death
TLS prophylaxis
Allopurinol
- prevents conversion of hypoxanthine and xanthine to uric acid
hydration
Rasburicase
- only for high risk + pre-existing hyperuricemia
TLS Management:
Hyperuricemia
IV hydration
Rasburicase
TLS Management:
Hyperkalemia
EKG -> rule out active arrhythmia
sodium polystyrene sulfonate
insulin & glucose
dialysis
TLS Management:
Hyperphosphatemia
phosphate binders
- sevelamer
- calcium acetate
dialysis
TLS Management:
Hypocalcemia
DO NOT TREAT
Anthracycline (daunorubicin, idarubicin, mitoxantrone) Clinical Pearls
ADE:
- red urine / sclera
- Mitoxantrone: blue-green urine
- myelosuppression
- cardiac toxicity
Cytarabine Clinical Pearls
ADE:
- neurotoxicity -> “neuro checks” required prior to each dose
- conjunctivitis
GO Clinical Pearls
ADE:
- infusion rxns -> pre-medicate with APAP, diphenhydramine, and methylprednisolone
- BBW hepatotoxicity
Low intensity chemo Clinical Pearls
ADE:
- constipation -> standing bowel meds
- low to moderate emetogenicity -> pre-med with ondansetron
G-CSF
Filgrastim
Sargramostim
Use: severe infections in setting of neutropenia
May be started after day 14 bmbx in pts receiving intensive chemo
ADE:
- bone pain -> manage with loratadine or hydroxyzine
- fever
- injection site rxn
- risk of potentiating leukemic cells
Chronic Myeloid Leukemia Treatment
Tyrosine Kinase Inhibitors
- goal: complete cytogenic response within 12 months
- if complete hematologic response not achieved within 3 months -> change therapy
Tyrosine Kinase Inhibitors
1st gen: Imatinib
2nd gen: Dasatinib, Nilotinib
3rd gen: Bosutinib, Ponatinib
STAMP inhibitor (targets ABL1 Myristoyl Pocket): Asciminib
Imatinib (Gleevec)
First gen TKI
MOA: selective inhibitor of BCR-ABL tyrosine kinase
Dosing: 400mg PO QD
- doses > 400 are not recommended in new patients -> more side effects, dose interruptions and higher rates of non-compliance
Some resistance has been developed to this drug -> try newer TKI
ADE:
- Edema/fluid retention
- myalgias
- hypophosphatemia
- GI (diarrhea, N/V)
Dasatinib (Sprycel)
2nd Gen TKI
MOA: dual inhibitor of BCR-ABL and Src family of kinases
MUCH more potent than imatinib
ADE:
- Pleural/pericardial effusions
- bleed risk
- pulmonary arterial hypertension
Nilotinib (Tasigna)
2nd gen TKI
more potent than imatinib
BBW: QTc prolongation
ADE:
- elevated pancreatic enzymes
- indirect hyperbilirubinemia
- QTc prolongation
- Cardiovascular events
Bosutinib (Bosulif)
3rd gen TKI
MOA: dual activity against BCR-ABL, Src, Lyn, and Hck kinases
- activity against many BCR-ABL mutations that are resistant to imatinib, dasatinib, and nilotinib
ADE:
- GI (Diarrhea, N/V)
- headache
- rash
CML Preferred initial treatments in low risk patients
First gen: Imatinib
OR
Second gen:
- Dasatinib
- Nilotinib
Contraindicated mutations in TKI treatment
Bosutinib: T3151, V299L, G25E, F317L
Dasatinib: T3151/A, F317L/V/I/C, V299L
Nilotinib: T3151, Y253H, E255K/V, F359V/C/I, G250E
Asciminib, Ponatinib, Omacetaxine, allo HCT, clinical trial: None
Ponatinib (Iclusig)
Third gen TKI
Active against all BCR-ABL point mutation INCLUDING: T315I
BBW: vascular occlusion, heart failure, hepatotoxicity
ADE:
- elevated pancreatic enzymes
- hypertension
- skin toxicity
- thrombotic events
Asciminib (Scemblix)
STAMP inhibitor
targets the ABL1 Myristoyl Pocket
Allosteric inhibitor
Indication: for pts who have previously received 2+ TKIs or those with T315I mutation
Omacetaxine mepesuccinate (Synribo)
FDA approved for patients with resistance and/or intolerance or two or more TKIs
MOA: reversible inhibitor of protein synthesis
ADE:
- myelosuppression
- nausea
- diarrhea
- fever
CML Accelerated Phase Treatment
TKIs
- 2nd gen preferred (dasatinib, nilotinib, bosutinib)
- selection based on prior therapy and cytogenetics
Omacetaxine can be considered in cases of disease progression due to resistance or intolerance to 2+ TKIs
Allogenic transplant may be considered
CML Blast Crisis Treatment
TKI +/- chemotherapy followed by allogenic HSCT
chemo chosen based on subtype of disease
