Chemotherapy and Leukemias

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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

methotrexate

ALL consolidation

same as remission (maybe cytarabine, 6-MP)

ALL Maintenance

methotrexate and 6-MP, VCR and prednisone

Vincristine

vinca alkaloid, microtubule inhibitor (M phase specific), substrate for MDR pump (increased drug efflux), causes neurotoxicity

Prednison

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)

L-asparaginase

inhibits protein synthesis (makes Asp unavailable to malignant cells)

Methotrexate

folate antimetabolite (some liver and lung fibrosis)

6-MP

purine antimetabolite

Cytarabine

pyrimidine antimetabolite

cyclophoshamide

alkylating agent, hemorrhagic cystitis

AML

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)

CML

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)

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