Treosulfan

• Conditioning treatment prior to hematopoietic stem cell transplantation (HSCT):
  Treosulfan is indicated for use as a myeloablative conditioning agent in patients undergoing allogeneic HSCT for:
• Malignant hematologic diseases such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)
• Non-malignant diseases including thalassemia, sickle cell anemia, and other bone marrow failure syndromes
• Off-label uses:
  Sometimes used in conditioning regimens for other hematologic malignancies or disorders in clinical practice.

• Route: Intravenous infusion.
• Standard Adult Dose: 14 g/m²/day administered intravenously over 2 hours on three consecutive days (typically days –6, –5, and –4 before transplantation), for a total cumulative dose of 42 g/m².
• Pediatric Dose: Similar dosing adjusted for body surface area; clinical judgment required.
• Special Populations:
• Renal impairment: Use caution; limited data available; monitor renal function closely.
• Hepatic impairment: Cautious use advised; monitor liver enzymes.
• Elderly: Dose adjustments may be necessary due to increased susceptibility to toxicity.
• Administration Notes: Ensure adequate hydration before and after infusion; premedicate with antiemetics as needed.

Treosulfan is a prodrug that undergoes spontaneous conversion in physiological conditions to active epoxide compounds. These reactive epoxides alkylate DNA, causing crosslinking of DNA strands, which prevents DNA replication and transcription, ultimately leading to apoptosis of rapidly dividing hematopoietic and malignant cells. This cytotoxicity results in myeloablation, making treosulfan effective as a conditioning agent to prepare the bone marrow for transplantation.

• Absorption: Administered intravenously; complete bioavailability.
• Distribution: Volume of distribution approximately 0.3–0.4 L/kg; low plasma protein binding.
• Metabolism: Non-enzymatic conversion to active epoxide metabolites; minimal hepatic metabolism.
• Half-life: Plasma half-life of parent drug around 1.5 hours; active metabolites persist longer.
• Excretion: Eliminated mainly by the kidneys (~40%) and in feces (~40%) as inactive metabolites.

• Pregnancy: Category D (FDA) — Evidence of fetal risk; use only if potential benefits justify the risks.
• Lactation: Unknown if excreted in human milk; breastfeeding is not recommended during therapy and for a time afterward.

• Antineoplastic agent
• Alkylating agent (bifunctional)
• Myeloablative conditioning agent

• Hypersensitivity to treosulfan or any excipients.
• Severe hepatic impairment.
• Active infections or medical conditions that contraindicate stem cell transplantation.

• Myelosuppression: Severe, prolonged bone marrow suppression is expected; close hematologic monitoring required.
• Infections: Immunosuppression increases risk; prophylactic antimicrobials recommended.
• Hepatotoxicity: Risk of veno-occlusive disease; monitor liver function tests regularly.
• Renal toxicity: Monitor renal function before, during, and after treatment.
• Infusion reactions: Watch for hypersensitivity; have emergency treatment available.
• Secondary malignancies: Possible with long-term use; monitor accordingly.

• Common: Nausea, vomiting, mucositis, diarrhea, fatigue, alopecia, myelosuppression (anemia, neutropenia, thrombocytopenia), fever.
• Serious: Hepatic veno-occlusive disease, severe infections, renal impairment, infusion-related hypersensitivity reactions.
• Rare: Cardiotoxicity, secondary cancers.

• Additive myelosuppression when used with other chemotherapeutic agents or radiation therapy.
• No significant cytochrome P450 interactions reported.
• Caution with nephrotoxic or hepatotoxic drugs due to overlapping toxicities.

• Treosulfan increasingly preferred over busulfan in conditioning regimens due to a more favorable toxicity profile, especially in pediatric and elderly patients.
• Guidelines recommend individualized dosing and intensive monitoring to reduce transplant-related complications.
• Ongoing clinical trials exploring combination therapies and long-term outcomes.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Do not freeze.
• Use freshly prepared solutions promptly, following manufacturer guidelines.