Treosulfan is a chemotherapy drug, an alkylating agent, primarily used as a conditioning agent before stem cell transplantation. This medication helps prepare the body for complex medical procedures, creating a suitable environment for new cells. It was authorized for medical use in the European Union in June 2019 and approved in the United States in January 2025.
Understanding Treosulfan and Its Mechanism
Treosulfan is an alkylating agent and a prodrug, meaning it is initially inactive and requires transformation within the body to become effective. This conversion happens spontaneously under physiological conditions, forming active compounds called epoxides, specifically monoepoxide and L-diepoxybutane. These active epoxide metabolites interact with cellular DNA, forming covalent bonds that create cross-links within the DNA strands. This cross-linking interferes with DNA replication and transcription, processes necessary for cell division and normal cellular function. By disrupting these processes, treosulfan induces programmed cell death, or apoptosis, particularly in rapidly dividing cells such as cancer cells and bone marrow cells.
Conditions Treosulfan Treats
Treosulfan is primarily used as a conditioning treatment before allogeneic hematopoietic stem cell transplantation (HSCT). This helps clear existing bone marrow, making space for transplanted stem cells to engraft and produce healthy blood cells. It is commonly used in combination with fludarabine for this purpose.
Conditions for which treosulfan is prescribed include certain blood cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in adults and pediatric patients generally aged one month or older. Treosulfan has also been investigated for use in other severe disorders requiring a bone marrow transplant, including non-malignant diseases. Historically, treosulfan was used for the treatment of ovarian cancer.
How Treosulfan is Administered and Its Side Effects
Treosulfan is administered intravenously, typically as a two-hour infusion. For conditioning regimens before HSCT, it is usually given on three consecutive days, often starting on day -4 before the stem cell infusion on day 0. Patients are often premedicated with antiemetics to manage nausea and vomiting.
Common side effects include infections, nausea, vomiting, stomatitis (inflammation of the mouth lining), diarrhea, abdominal pain, musculoskeletal pain, swelling, and fever. Lab abnormalities such as increased levels of bilirubin, ALT, AST, and GGT can occur. Profound myelosuppression (a decrease in blood cell counts) is a significant and expected side effect, as it is the intended therapeutic effect for preparing the bone marrow for transplantation.
More serious side effects include an increased risk of secondary malignancies, particularly leukemia, especially in patients with certain DNA breakage disorders. Seizures have also been reported. Skin reactions like rash, itching, or dryness can develop, and injection site reactions such as swelling, pain, or burning may occur. In pediatric patients, diaper dermatitis may occur due to treosulfan excretion in urine, requiring frequent diaper changes.
Key Considerations for Patients
Patients receiving treosulfan require close medical supervision and frequent monitoring. Blood cell counts, including differential and platelet counts, should be monitored daily until the hematopoietic system recovers following transplantation. This monitoring helps manage expected profound myelosuppression and increased infection risk.
Healthcare providers will consider prophylactic or empiric anti-infective treatments (bacterial, viral, fungal) to mitigate infection risk during periods of severe neutropenia. Patients should communicate any new or worsening symptoms to their healthcare team promptly. Females of reproductive potential are advised to use effective contraception during and for a period after treatment, and males with female partners of reproductive potential should also use contraception.