acute and chronic myeloid leaukemia Flashcards
risk factors for AML
- inc age
- prior chemo
- cigarette smoking
- radiation, benzene, pesticide and petrochemical exposure
how to diagnose AML and what is required
- how: Bone marrow biospy, Echo/EKG, D/C panel (PT, fibrinogen), CNS imaging, TLS
- Required: 20% and up blast or cytogenetic abnormalities (translocations, deletions, etc.)
AML Prognostic markers
- predicts pt ability to obtain/ stay/survive in remission w/ induction chemo
-performance status, age, comorbidities, primary vs econdary AML, WBC at diagnosis
S/S AML
- anemia (↓ RBC) → give blood transfusions
- thrombocytopenia (bleed risk) → give platelets
- neutropenia (risk of inf)
- TLS
- CNS involvement (rare)
- hyperleukocytosis (↑ WBC > 100,000)
what is and how to treat hyperleukocytosis in AML; pearls of med , ae
- Oncologic emergency; hyperviscosity syndrome → blood sludging
- stroke, resp failure, cardiac ischemia, renal failure, retinal hemorrhage
- Hydroxyurea - titrate based on WBC count and response (takes ~5 days) → acute: mouth sores, GI; long term: aleopica, hyperpig, ulceration, mucositis
Targeted mutation therapies AML, what to do if patient refractory
- FLT3-ITD ← Quizatinib, Midostaurin
- FLT3- TKD ← Midostaurin
- if they didnt recieve Venetoclax + Azacitidine GIVE
- FLT3 relapse/refractory ← Gilteritib
- IHD1 ← Ivosidenib
- IDH2 ← Enasidenib
goal of induction chemo therapy (high intensity and who gets it) AML
- get rid of macrodisease
- <60, >60 w/o significant comorbidities , good performance
- pts w/ aggressive disease (hyperleukocytosis, TLS at pres)
- candidates for allogenic stem cell transplant
Chemo therapy time frame/ clinical pres AML
- day 1-7 chemo admin, dramatically WBC drop
- day 8-24 cell count nadir (WBC=0) & recovery; platelet transfusion required
- day 25+ complete cell recovery, discharge whenANC>500 and platelets good
what are our high intensity induction options
- Cytarabine continuous IVX 7 days + Daunorubicin or Idarubicin x 3 days
- Liposomal Duanrobicin + Cytrabine (2ndary leaukemia)
- clinical trials
what is the criteria for complete remission w/ complete response- day 28+ AML
<5% blast + ANC >1000 +platelets >100,000
what is the criteria for leukemia free state - day 14 AML
- after 2nd bone biopsy patient should have <5-10% blast and be hypocellular (no more hyperviscosity/blood slugging)
low intensity options
- Hypomethylating agents (Azacitidine, Decitabine) + Venetoclax
- low dose cytrabine (~50) + Venetcolax
- Ivosidenib + Ventetoli
- Gemtuzumab Ozo (add on)
who gets allogeneic stem cell transplant
- Intermediate + poor risk disease
- 2nd or treatment related AML
- fit enough
- complete induction & 1 or more cycles of consolidation
clinical peatl of quizaritinib
causes qt prolongation, dose adj for DDIs
midostaurin clinical pearls
BID, poorly tolerated, stinks, FDA approved newly diagnosed ITD
who is liposomal Duanorubicin + Cytarabine a good opion for
2ndary leukemias
Clinical pearls of HMAs (Azacitidine, Decitabine, Venetoclax)
Severe constipation, start bowel regimen
- Venetoclax: DDIs, myleosuppression
clinical pearls of gemtuzumab
- monoclonal antibody
- inflammation related syndrome pre med w/methyl
Clinical pearls of cytarabine
- neurotoxicity
- head and foot syndrome
- conjugivitis (give dexa eye drops 3 days a/f. treatment)
what
clinical pearls for anthracyclines (Duanrubicin)
- Cardiac toxicity
what is post AML remission therapy aka consolidation therapy
- High dose Cytarabine (HiDac)
- Liposomal duanorubicin + cytarabine
Clinical pearls of Anthracyclines
- cardiac toxicity→ HF
- lifetime dose
- significant WBC
myeloid growth factors
- dec chemo recovery time
- agents: filgrastim
- bone pain : give loratidine or hydroxyzine
- used w/ neutropenia concerns
supportive care for infections prophylaxis AML
give coverage for each
- HSV/VZV: Acyclovir
- Antibacterial: Cipro or Levo or Augmentin
- Invasive Fungal: Posaconazole, Voriconazole
CML diagnosis
Philadelphia Chromosome PH + (translocation of 9 and 22) which causes that formation of BCR-ABL, Causing proliferation
Tyrosine Kinase inhs and clinical pearls, aes CML
- Imatinib: peripheral edema
- Dastinib: edema in lungs (plureal), AVOID PPIs + H2RAs (needs acidic environment)
- Nilotinib: empty stomach BLACK BOX: QT prolongation
- Asciminb: empty stomach
- Bosutinib: Diarrhea (give loperamide) subsides
- Ponatinib: BLACK BOX: Hepatoxicity, HF, vacular occulsions) - Aspirin prophylaxis
Why might someone have TKI resistance and how to treat
- Gatekeeper mutation : T3151→Asciminib, Ponatinib
Monitoring for CML
gold standard: achieve complete cytogenetic response w/in 12 months
how to treat accelerated phase
- Treat w/ TKIs w/ inc doses
- consider allogenic transplant
How to treat blast phase
TKI +/- Chemo then allogenic stem cell transplant
how to choose CML agent
- Low risk: Imatinib, Bosutinib, Dosatinib, Nilo
- Intermediate- high risk: Bosutinib, Dasatinib, Nilotiinib
