• Central Access is absolutely contraindicated in APL
  • central line access for leukapheresis can increase cell shearing which releases the pro-coagulants stored in APL cancer cells (exacerbates the already ongoing DIC)
• Watch out for differentiation syndrome when undergoing ATRA + Arsenic treatment
• Q Mon and Thursday EKG to watch QTc
• Keep patient on aggressive electrolyte protocol: K>4, Mg>2

Medications

Chemotherapies

• Tyrosine Kinase Inhibitors (TKI) absorption are decreased by PPI, H2 blockers, and calcium carbonate (if using TUMS, space out a few hours after)
• Daunorubicin: anti-mitotic, anti-tumor and cytotoxic anthracycline antibiotic and maintains the stability of DNA-topoisomerase II complex which prevents topoisomerase II from catalyzing the re-ligation part of the ligation-religation reaction leading to single and double strand DNA breaks.
  • Acute or subacute cardiotoxicity can develop within 1 to 23 days after the last dose
  • Conduction or rhythm disturbances (ie, tachycardia, supraventricular dysrhythmias, heart block) and abnormal ECG findings (nonspecific ST-T changes)
  • Significant decrease in ejection fraction has been documented 24 to 48 hours after drug administration.
  • Irreversible congestive heart failure, the mortality rate ranges from 50% to 80%
• Cytarabine: aka Ara-C. Cell cycle phase specific antineoplastic agent, affecting cells only during the S-phase of cell division. Once in the cell, cytarabine is converted into cytarabine-5'-triphosphate (ara-CTP), which is the active metabolite and holds the cell in the S-Phase. Also inhibits DNA/RNA polymerase.
  • Hi-DAC (high dose ARA-C): risk of cerebellar toxicity, perform cerebellar testing daily with Finger-to-Nose testing (and other cerebellar testing) and for 48 hours after
  • Keratoconjunctivitis: to prevent, patients are treated with refresh eye drops (2 drops both eyes every 4 hours) and Pred Forte (prednisolone acetate ophthalmic suspension, 2 drops both eyes every 4 hours) until at least 24 hours following last dose of HiDAC.
  • Can see fevers with HiDAC at times but do not want to miss infection either. If fevers related to HiDAC, typically add hydrocortisone 100 mg IV to the chemotherapy mix
• Midostaurin (RYDAPT): Inhibitor of multiple receptor tyrosine kinases and has the ability to inhibit FLT3 receptor signaling and cell proliferation.
  • Approved in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation, to treat newly-diagnosed acute myeloid leukemia in adult patients with an FLT3 mutation.
  • FLT3 = expressed on the surface of many hematopoietic progenitor cells and plays role in cell survival, proliferation, and differentiation
• Ivosidenib: isocitrate dehydrogenase-1 (IDH1) inhibitor of mutants which leads to decreased 2-hydroxyglutarate (2-HG) in leukemia cells, reduced blast counts, and increased percentages of mature myeloid cells .
  • Newly-diagnosed, susceptible IDH1- mutation; in patients 75 years or older or with comorbidities that preclude intensive induction chemotherapy
• Vyxeos: Liposomal formulation of Cytarabine + Daunorubicin (provide further coverage with posaconazole due to increased risk for fungal infection)
• Venetoclax: Inhibitor of beta cell lymphoma-2 (bcl-2), an anti-apoptotic protein. Restores apoptosis by binding to the BCL-2 protein in leukemia cells, triggers mitochondrial outer membrane permeability and activation of caspases
  • Dose reduced by 50% with fluconazole and 75% if posaconazole or voriconazole due to pharmacokinetic interference
  • BIOCHEMISTRY FUN:
    • B-cell lymphoma 2 (BCL-2) protein plays a key regulator of the mitochondrial apoptotic pathway. BCL-2 maintains myeloblast survival by sequestering pro-apoptotic BAX, resulting in mitochondrial dependence on BCL-2. BAX is released when BCL-2 is antagonized, resulting in mitochondrial outer membrane permeabilization and cell death
    • Venetoclax promotes cancer cell death by blocking the BCL2 protein
• Acitabine
• Decitabine: Hypomethylation of DNA and cellular differentiation or apoptosis.
• Peg asparaginase
  • Can cause intrahepatic cholestasis which causes build-up of conjugated bilirubin and pressure build-up causes back-flow into systemic circulation
  • If on treatment and related liver injury, important to rule out venous occlusive disease (VOD) aka sinusoidal obstructive disease (SOD) -> via imaging for obstruction
• Gilteritinib: Inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3).
• Vincristine: arrest of replicating cells at the metaphase stage through prevention of microtubule formation in the mitotic spindle.
• Cyclophosphamide: alkylating agent, cytotoxic action is primarily due to cross-linking of strands of DNA and RNA, as well as to inhibition of protein synthesis.