Chemotherapy and Leukemias

acute Lymphocytic Leukemia stages
primarily childhood (ages 1-10)
remission induction (1-2 months;absence of symptoms, absence of hematologic alterations)> CNS prophylasis (1 month; high metastasis to the brain; continue throughout if pediatric)> consolidation (3-9 months; intensification; done to ride body of the cells)> Maintenance (30-36 months)
ALL remission induction drugs
vincristine, prednison, anthracuclin, L-asparaginase with peds
ALL CNS prophylaxis
ALL consolidation
same as remission (maybe cytarabine, 6-MP)
ALL Maintenance
methotrexate and 6-MP, VCR and prednisone
vinca alkaloid, microtubule inhibitor (M phase specific), substrate for MDR pump (increased drug efflux), causes neurotoxicity
corticosteroid, suppresses gene expression, Cushin-like effects and psychosis
Anthracycline (-rubicin)
intercalating agent and topoisomerase2 inhibitor (decreases DNA repair), free radicals, MDR substrate, cardiotoxicity (arrythmias; accumulation= CHF)
inhibits protein synthesis (makes Asp unavailable to malignant cells)
folate antimetabolite (some liver and lung fibrosis)
purine antimetabolite
pyrimidine antimetabolite
alkylating agent, hemorrhagic cystitis
disease increases with age (recurrence after age 60)
remission induction> consolidation . HSC ttransplant (if drug tx if not curative) or dictontinue therapy
AML remission induction
cytarabine and daunorubicin (7 and 2 regimen) and an etoposide if pediatric cases
AML consolidation drugs
same as ALL
Acute Promyelocytic Leukemia
ATRA is first choice (in t(15,17): promotes cellular differentiation and reduces proliferation
Arsenic trioxide (increased degradation of product of mutation): promotes differentiation, induces apoptosis
gemtuzumab (CD33 antibody)-ozogamicin (antibody intercalating agent)
in 50s nd 60s
Imatinib (ABL tyrosine kinase inhibitors; not curative)
Interferon- (alpha- antiproliferative agent), plus cytarabine
Hydroxyurea ( inhibits DNA synthesis; ribonucleaotide reductase)
Chronic Lymphocytic Leukemia
disease of the elderly, chronic environmental exposure
Fludaribine or cladribine (purine analog; inhibitor of DNA synthesis) plus cyclophosphamide OR
cyclophosphamide and prednisone (suppresses cellular signaling) often PLUs
Rituximab (mab to CD20; mouse/human) OR
Alemtuzumab (mab to CD 53) or Ofatumumab (CD 20)