TREATMENT

Phases of treatment Induction chemotherapy Postremission therapy *Initial goal: quickly induce CR *Therapy depends on patient age

Induction chemotherapy Cytarabine + anthracycline – Mode of action: Cytarabine – s-phase specific antimetabolite, interferes w/ DNA synthesis Anthracycline – DNA intercalators, inhibit topoisomerase II leading to DNA breaks – Adminitration: Cytarabine – continuous IV infusion for 7 days Anthracycline (daunorubicin) – IV on days 1,2 & 3 (the 7 & 3 regimen) * cytarabine + idarubicin – may be superior to danaurubicin in younger patients * addition of etoposide – may improve CR duration

Induction chemotherapy Cytarabine toxicity – Myelosupression – Pulmonary toxicity – Irreversible cerebellar toxicity Occur more commonly in patients w/ renal impairment or those over the age of 60

Induction chemotherapy Bone marrow exam after induction therapy – Determine if leukemia has been eliminated – >5% blast w/ >20% cellularity – re-treat patient – Failed to attain CR after 2 induction – allogeneic stem cell transplant

Supportive Care Recombinant hematopoietic growth factors – To lower infection rate – For elderly patients w/ complicated courses, those receiving post remission regimens, patients w/ uncontrolled infections, those participating in clinical trials Multilumen right atrial catheters – For administration of IV medications and transfusions, for blood drawing Adequate prompt blood bank support – Platelet transfusion – maintain at >10,000-20,000/μL – RBC transfusion – Hg level >8g/dL

Complications Infections – major cause of morbidity and death – Candidiasis – oral nystatin, clotrimazole – Herpes simplex virus – acyclovir Fever – Empirical broad spectrum antibacterial & antifungal antibiotics Imipenen-cilastin Antipseudomonal semisynthetic penicillin + aminoglycoside Third generation cefalosporin w/ antippseudomonal activity Double β lactam combinations

Treatment of PML Tretinoin – Induces differentiation of leukemic cells bearing the t(15;17) – Complication: retinoic acid syndrome Fever, dyspnea, chest pain, pulmonary infiltrates, pleural and pericardial effusion, hypoxia Treatment: glucocorticoids, chemotherapy, supportiveb measures Cytarabine + daunorubicin – Complication: DIC Tretinoin + anthracycline – Safest and most effective treatment Arsenic Trioxide *RT-PCR amplification of the t(15;17) chimeric gene - predict relapse

Postremission Therapy To eradicate residual leukemic cells to prevent relapse and prolong survival – Intensive chemotherapy – Allogeneic or autologous SCT

Relapse Patients are rarely cured w/ further standard dose therapy – Allogeneic SCT – for eligible patients – Autologous SCT rescue Factors predicting response at relapse: – Length of previous CR – Initial CR was achieved w/ 1 or 2 courses of chemotherapy – Type of postremission therapy Patients have poor outcome

Relapse Innovative approaches – new drugs or immunotherapy Decitabine – Elderly patients Gemtuzumab ozogamicin – Toxicity – myelosuppression, infusion toxicity, venoocclusive disease – Pretreatment w/ glucocorticoids