TREOSULFAN INJ,LYPHL
Clinical Criteria Summary
Indication
- In combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
Patient Population & Eligibility Criteria
- Age 18-70 years
- Patients with AML in first or consecutive hematologic remission (blast count < 5% in marrow) or MDS (blast count < 20% in marrow)
- Eligible for alloHSCT but at increased mortality risk for myeloablative conditioning (MAC) based on age > 50 years, HCT-comorbidity index (HCT-CI) > 2, or both
- Karnofsky index > 60%
- Availability of an HLA-identical matched related donor (MRD) or HLA-identical matched unrelated donor (MUD)
Exclusion Criteria
- Prior alloHSCT
- Active and uncontrolled infection
- Creatinine clearance (CrCl) < 60 ml/min
- FEV1 < 50% or requirement for supplemental oxygen
- Left ventricular ejection fraction (LVEF) < 40%
- Total bilirubin > 3x upper limit of normal (ULN) or ALT/AST > 5x ULN
Dosing & Administration
- Treosulfan 10 g/m2 IV daily x 3 days (day -4, -3, -2) with Fludarabine 30 mg/m2/day IV daily x 5 days (day -6, -5, -4, -3, -2)
- Doses higher than recommended are associated with increased early morbidity and mortality
Contraindications
- Hypersensitivity to any component of the drug product
Warnings & Precautions
- Risk of severe and prolonged myelosuppression (HSCT is required to prevent potentially fatal complications)
- Seizures
- Skin disorders
- Injection site reactions and tissue necrosis
- Secondary malignancy
- Embryo-fetal toxicity
Pregnancy, Lactation & Reproductive Requirements
- Conduct pregnancy test in females of reproductive potential within 7 days of start
- Advise females and males with partners of reproductive potential to use effective contraception during treatment and for 3 months following
- Advise women not to breastfeed during treatment and for one week following
Organ Impairment Considerations
- Mild renal impairment: No clinically significant differences in PK profile; unknown in moderate or severe renal impairment
- Mild hepatic impairment: No clinically significant differences in PK profile; unknown in moderate or severe hepatic impairment
Place in Therapy / Regimen Classification
- Classified as a myeloablative conditioning (MAC) regimen
- Considered the preferred standard preparative regimen for older, comorbid patients with AML or MDS undergoing alloHSCT