AZACITIDINE INJ,LYPHL
Clinical Criteria Summary
Diagnosis & Initial Therapy
- Initial therapy for myelodysplastic subtypes: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), chronic myelomonocytic leukemia (CMMoL)
- Must be accompanied by neutropenia OR thrombocytopenia OR clinical hemorrhage requiring platelet transfusions OR anemia requiring red blood cell transfusions
- Restricted to use by VA Hematologists and Oncologists
Exclusion Criteria
- ECOG Performance Status >2
- Serum Creatinine > 1.5 X ULN
- Diagnosis of metabolic acidosis
- Total bilirubin > 1.5 X ULN
- AST/ALT > 2 X ULN
- Extensive hepatic tumor burden due to metastatic disease
- Uncontrolled congestive heart failure
- Hypersensitivity to mannitol
- Life expectancy < 4 months
- Pregnancy
- Women actively breastfeeding
Discontinuation Criteria
- Progression of disease during initial 4 months of treatment
- Stable disease after initial 4 months of treatment
- Unacceptable toxicity
- Relapse after initial response:
- • >5% myeloblasts in bone marrow (from complete response)
- • >30% bone marrow blasts (from partial response)
- • Return of peripheral blood counts to pretreatment values or recurrence of transfusion requirements (from improvement)
- Transformation to Acute Myelogenous Leukemia
Monitoring
- Complete blood counts and assessment of renal function prior to each cycle and as needed
- Premedicate with oral prochlorperazine or oral ondansetron
- If no beneficial bone marrow effect from initial dose by day 57 without significant toxicity, increase dose to 100mg/m2/day for 7 days (optional)
- Assess effect on bone marrow after fourth cycle (day 113) (optional)
- Reduce dose by 50% on next course for unexplained reductions in serum bicarbonate to < 20 mEq/L; assess for renal tubular acidosis (alkaline urine, hypokalemia to <3 mEq/L along with drop in serum bicarbonate)
- If unexplained increase in BUN or serum creatinine, delay dose until values return to normal or baseline, then resume at 50% dose reduction on next course
Additional Definitions & Requirements
- Neutropenia defined as ANC <1.0 x 109/L and thrombocytopenia defined as platelets ≤50 x 109/L
- Women of child-bearing potential and men with the potential to father a child should use adequate contraception methods