Treosulfan — Drug Monograph
Brand names: Grafapex
Drug class: Alkylating Agent
Mechanism of Action
Bifunctional DNA-alkylating (busulfan-related) prodrug. Under physiologic conditions treosulfan converts non-enzymatically to reactive epoxide intermediates that alkylate and cross-link DNA, producing potent myeloablative and immunosuppressive activity that clears host hematopoiesis to enable donor engraftment. Its predictable, pH- and temperature-dependent (non-enzymatic) activation gives more consistent exposure than busulfan and does not require therapeutic drug monitoring.
FDA Indications
- In combination with fludarabine as a preparative (conditioning) regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) (FDA approved January 21, 2025; MC-FludT.14/L Trial II: overall survival HR 0.67 vs busulfan-fludarabine)
Common Side Effects
- Musculoskeletal pain
- Stomatitis/mucositis
- Pyrexia
- Nausea
- Edema
- Infection
- Vomiting
- Myelosuppression (expected/intended)
Clinical Pearl
Treosulfan (with fludarabine) is a myeloablative conditioning backbone that improved overall survival versus busulfan-fludarabine in older or comorbid AML and MDS patients (MC-FludT.14/L). Its non-enzymatic, exposure-predictable activation means - unlike IV busulfan - no pharmacokinetic therapeutic drug monitoring or PK-guided dose adjustment is needed, simplifying conditioning in a higher-risk transplant population.
Related Therapies & Mechanisms
- Bendamustine (Treanda) — Alkylating Agent · Leukemia
- Busulfan (Busulfex) — Alkylating Agent · Leukemia
- Chlorambucil (Leukeran) — Alkylating Agent · Leukemia
- Cyclophosphamide (Cytoxan) — Alkylating Agent · Leukemia