Trecondi: Uses, Dosage & Side Effects
An alkylating agent used as conditioning treatment before allogeneic hematopoietic stem cell transplantation in adults and pediatric patients
Trecondi (treosulfan) is a cytotoxic alkylating agent administered intravenously as part of a conditioning regimen before allogeneic hematopoietic stem cell transplantation (alloHSCT). It works by destroying the patient's existing bone marrow cells to enable engraftment of donor stem cells. Trecondi is approved for use in adults and in children over one month of age with both malignant and non-malignant diseases.
Quick Facts
Key Takeaways
- Trecondi (treosulfan) is used exclusively in hospital settings as a conditioning treatment before allogeneic hematopoietic stem cell transplantation (bone marrow transplant).
- It is always given in combination with fludarabine (and in children, usually also with thiotepa) as an intravenous infusion over 2 hours on 3 consecutive days.
- The drug deliberately destroys existing bone marrow cells (myeloablation) to allow donor stem cells to engraft and produce healthy blood cells.
- Severe reduction in blood cell counts is the expected, intended effect, and patients require intensive monitoring and supportive care including antibiotics, antifungals, and antivirals.
- Trecondi may cause permanent infertility; fertility preservation should be discussed before treatment begins.
What Is Trecondi and What Is It Used For?
Trecondi (treosulfan) belongs to a group of medicines known as alkylating agents. These are cytotoxic drugs that work by damaging the DNA of cells, which prevents them from dividing and ultimately leads to cell death. In the context of stem cell transplantation, this myeloablative action is specifically desired: the drug destroys the patient's existing bone marrow cells, creating space for new donor stem cells to engraft and begin producing healthy blood cells.
The primary indication for Trecondi is as part of a conditioning regimen before allogeneic hematopoietic stem cell transplantation. Allogeneic HSCT involves replacing a patient's diseased or damaged bone marrow with healthy stem cells from a compatible donor. This procedure is used to treat a wide range of serious conditions, including various blood cancers (such as leukemia, lymphoma, and myelodysplastic syndromes) as well as non-malignant diseases such as severe aplastic anemia, primary immunodeficiency disorders, and inherited metabolic diseases.
Trecondi has been approved for use in the European Union based on clinical trial data demonstrating that treosulfan-based conditioning regimens provide effective myeloablation with a potentially more favorable toxicity profile compared to traditional busulfan-based conditioning in certain patient populations. The pivotal MC-FludT.14/L randomized controlled trial showed that treosulfan-based conditioning was non-inferior to busulfan-based conditioning in terms of event-free survival, while demonstrating potentially lower rates of certain toxicities.
The drug is approved for use in adults, as well as in adolescents and children older than one month of age. This broad age range reflects the importance of stem cell transplantation across pediatric populations, where conditions such as inherited immune deficiencies, hemoglobinopathies (like sickle cell disease and thalassemia), and certain metabolic storage disorders may necessitate HSCT as the only curative treatment option.
Trecondi must only be administered under the supervision of a physician experienced in conditioning regimens and hematopoietic stem cell transplantation. Treatment is given in specialized transplant centers equipped to manage the complex supportive care requirements that follow myeloablative conditioning.
What Should You Know Before Taking Trecondi?
Contraindications
Trecondi is absolutely contraindicated in the following situations. Your treating physician will perform thorough evaluations before initiating therapy to ensure none of these conditions apply:
- Allergy to treosulfan: If you have a known hypersensitivity to treosulfan or any component of the formulation, the drug must not be administered.
- Active uncontrolled infection: Any ongoing infection that is not adequately controlled with antimicrobial therapy is a contraindication, as myeloablative conditioning would severely compromise the immune system's ability to fight the infection.
- Severe organ dysfunction: Significant impairment of cardiac, pulmonary, hepatic (liver), or renal (kidney) function may preclude the safe use of Trecondi, as these organs are essential for processing and eliminating the drug and managing the transplant process.
- Inherited DNA repair disorders: Conditions such as Fanconi anemia that impair the cell's ability to repair DNA damage significantly increase the risk of severe toxicity from alkylating agents, making treosulfan contraindicated in these patients.
- Pregnancy: Trecondi must not be given to pregnant women or women who suspect they may be pregnant due to the risk of serious harm to the developing fetus.
Warnings and Precautions
Trecondi is a potent cytotoxic medication, and several important warnings apply during treatment. Regular blood tests will be performed throughout the treatment course and recovery period to monitor blood cell counts and organ function:
At the recommended dose, Trecondi causes severe myelosuppression (reduction in blood cell counts), which is the intended therapeutic effect. This means patients will experience a period of very low white blood cells (increasing infection risk), low platelets (increasing bleeding risk), and low red blood cells (causing anemia). Intensive monitoring and supportive care are essential during this critical period.
To prevent and treat infections during the period of profound immunosuppression, patients will receive prophylactic medications including antibiotics, antifungal agents, and antiviral drugs. The transplant team will closely monitor for any signs of infection and initiate appropriate treatment promptly.
Trecondi may increase the risk of developing secondary malignancies (new cancers) in the future. This is a known risk associated with alkylating agents and is a consideration that the transplant team will discuss with patients as part of the informed consent process. The benefits of the transplant procedure typically far outweigh this long-term risk.
Mucositis (inflammation and ulceration of the mucous membranes, particularly in the mouth) is a common side effect of treosulfan-based conditioning. Good oral hygiene practices are strongly recommended, and preventive measures such as therapeutic mouth rinses (barrier-protective or antimicrobial formulations) and oral cryotherapy (placing ice chips in the mouth during or after infusion to reduce blood flow to oral tissues) may help reduce the severity of this complication.
Live vaccines must not be administered during treatment with treosulfan or during the immunosuppressed period following transplantation. Your transplant team will provide specific guidance on when it is safe to resume vaccinations after transplantation.
Treosulfan may cause menopause-like symptoms in women, including absence of menstrual periods. This may be temporary or permanent depending on the patient's age and the specific conditioning regimen used.
Use in Children and Adolescents
Trecondi is approved for children and adolescents older than one month of age. However, certain age-specific considerations apply:
- Infants under 4 months: Seizures have been reported very rarely in this age group. Close neurological monitoring is essential.
- Children under 1 year: These patients may experience more severe respiratory side effects compared to older children. Enhanced respiratory monitoring is recommended.
- Infants in diapers: Diaper dermatitis with ulceration in the perianal area may occur because treosulfan excreted in urine can damage the skin. Diapers should be changed frequently during the 6-8 hours following each dose of the medication.
- Neonates under 1 month: There is insufficient data for use in this age group, and Trecondi is not recommended.
Pregnancy and Breastfeeding
Trecondi has the potential to cause serious harm to an unborn child. Women must not become pregnant during treatment and for at least 6 months after the last dose. Effective contraception must be used by both male and female patients of reproductive potential throughout the treatment period and for the recommended post-treatment interval.
Breastfeeding must be discontinued before starting treatment with Trecondi. It is not known whether treosulfan or its metabolites pass into breast milk, and given the cytotoxic nature of the drug, any exposure to a breastfed infant could be harmful.
Treosulfan may cause permanent infertility in both men and women. Patients who wish to have children in the future should discuss fertility preservation options with their physician before treatment begins. For men, sperm cryopreservation (sperm banking) should be considered. For women, options such as oocyte or embryo cryopreservation may be available, though these are dependent on the urgency of treatment and the patient's clinical situation.
Driving and Using Machines
Trecondi may cause nausea, vomiting, and dizziness, which can impair the ability to drive or operate machinery. Patients experiencing these symptoms should not drive or use machines. In practice, patients undergoing HSCT conditioning are hospitalized and this restriction is typically not applicable during the treatment period.
How Does Trecondi Interact with Other Drugs?
Drug interactions with treosulfan are clinically relevant primarily in the context of the transplant conditioning protocol. Because Trecondi is exclusively used in a controlled hospital setting as part of a defined treatment regimen, all concurrent medications are carefully managed by the transplant team.
The following table summarizes the key drug interactions and co-administered medications relevant to treosulfan-based conditioning:
| Interacting Drug | Type | Effect / Notes |
|---|---|---|
| Fludarabine | Required combination | Always given together as part of the conditioning regimen. Fludarabine provides immunosuppressive and cytotoxic effects that complement treosulfan's myeloablative activity. |
| Thiotepa | Common combination (pediatric) | Frequently added to the treosulfan/fludarabine regimen in pediatric patients. Provides additional myeloablative and immunosuppressive activity. |
| Live vaccines | Contraindicated | Live vaccines must not be given during treatment with treosulfan due to the risk of uncontrolled vaccine-strain infection in severely immunosuppressed patients. |
| Other cytotoxic agents | Caution | May potentiate myelosuppression and increase the risk of organ toxicity. Any concurrent use must be carefully evaluated by the transplant team. |
| Nephrotoxic drugs | Caution | Concurrent use with nephrotoxic agents (e.g., aminoglycosides, amphotericin B) may increase the risk of renal impairment. Renal function should be closely monitored. |
| Hepatotoxic drugs | Caution | Concurrent use with hepatotoxic agents may increase the risk of hepatic veno-occlusive disease (sinusoidal obstruction syndrome). Liver function should be carefully monitored. |
Patients should inform their transplant team about all medications they are taking, including prescription drugs, over-the-counter medications, herbal supplements, and vitamins. The transplant team will assess each medication for potential interactions and make appropriate adjustments to the treatment plan.
What Is the Correct Dosage of Trecondi?
Adults
Standard Adult Dosage
Trecondi is used in combination with fludarabine as part of the conditioning regimen. The recommended dose for adults is 10-14 g/m² body surface area (calculated from height and weight), administered as an intravenous infusion over 2 hours on each of 3 consecutive days before the stem cell infusion.
The total dose administered over the 3-day period is therefore 30-42 g/m². The specific dose within this range is determined by the treating physician based on the patient's condition, the underlying disease, and the transplant protocol being followed.
Children and Adolescents
Pediatric Dosage (over 1 month of age)
In children and adolescents, Trecondi is used in combination with fludarabine and, in most cases, also with thiotepa. The recommended dose is the same as for adults: 10-14 g/m² body surface area, administered as an intravenous infusion over 2 hours on 3 consecutive days.
Dosing in pediatric patients is carefully calculated based on body surface area, which accounts for both height and weight. Infants and young children will require particular attention to accurate weight measurement and dose calculation.
| Patient Group | Dose per Day | Duration | Combination |
|---|---|---|---|
| Adults | 10-14 g/m² BSA | 3 consecutive days | Fludarabine |
| Adolescents | 10-14 g/m² BSA | 3 consecutive days | Fludarabine + Thiotepa |
| Children (>1 month) | 10-14 g/m² BSA | 3 consecutive days | Fludarabine + Thiotepa |
| Neonates (<1 month) | Not recommended | N/A | Insufficient data |
How Trecondi Is Administered
Trecondi is administered exclusively in a hospital setting by trained healthcare professionals experienced in stem cell transplantation. The drug is supplied as a white crystalline powder in glass vials that must be reconstituted with sodium chloride solution (0.45%) before administration.
The reconstituted solution is given as an intravenous infusion over a period of 2 hours. Treatment is administered on 3 consecutive days, followed by the infusion of donor hematopoietic stem cells. The timing of the conditioning regimen relative to the stem cell infusion is carefully planned as part of the overall transplant protocol.
Missed Dose
Because Trecondi is administered in a controlled hospital setting as part of a strict transplant conditioning schedule, missed doses are extremely unlikely. The transplant team manages the entire administration process. If any dose adjustment or schedule modification is necessary, it will be determined by the treating physician based on the patient's clinical condition.
Overdose
As Trecondi is administered exclusively by trained healthcare professionals in hospital settings with precise dose calculations based on body surface area, overdose is unlikely. There is no specific antidote for treosulfan. In the event of overdose, treatment would be supportive, focusing on management of the expected consequences of excessive myeloablation, including profound cytopenias and their complications (infections, bleeding).
What Are the Side Effects of Trecondi?
Like all medicines, Trecondi can cause side effects, although not everybody gets them. Many of the side effects listed below are also consequences of the stem cell transplantation process itself and are managed by the specialized transplant team.
The most serious side effects of treosulfan treatment or the stem cell transplantation procedure include severely reduced blood cell counts (which is the intended effect of the conditioning regimen), serious infections caused by bacteria, viruses, and fungi, hepatic veno-occlusive disease (blockage of veins in the liver), and pneumonitis (lung inflammation). Your physician will regularly monitor blood values and liver enzymes to detect and manage these complications.
Side Effects in Adults
Very Common
May affect more than 1 in 10 patients
- Febrile neutropenia (low white blood cell count with fever)
- Mucositis (inflammation of mucous membranes, particularly in the mouth, which may cause ulcers)
- Diarrhea, nausea, vomiting
- Fatigue
- Increased bilirubin levels (a liver pigment, often indicating liver stress)
Common
May affect up to 1 in 10 patients
- Sepsis (blood poisoning)
- Allergic reactions
- Decreased appetite, insomnia
- Headache, dizziness
- Heart rhythm changes (irregular, fast, or slow heartbeat)
- High or low blood pressure, flushing
- Breathing difficulties, nosebleeds
- Oral pain, stomach inflammation, abdominal discomfort, constipation, difficulty swallowing, esophageal pain
- Maculopapular rash, purpura (red skin spots), erythema (skin redness), hand-foot syndrome, itching, hair loss
- Pain in arms or legs, back pain, bone pain, joint pain
- Sudden worsening of kidney function, blood in urine
- Edema (fluid retention causing swelling), fever, chills
- Increased liver enzymes, increased C-reactive protein, weight changes
Uncommon
May affect up to 1 in 100 patients
- Hepatic veno-occlusive disease (blockage of a vein in the liver)
- Pneumonitis (lung inflammation)
- Abnormal blood sugar levels
- Confusion
- Cerebral hemorrhage, peripheral sensory neuropathy (nerve problems in arms and legs causing numbness, tingling, or burning pain)
- Vertigo (spinning sensation)
- Bruising
- Fluid around the lungs, throat inflammation, laryngeal inflammation or pain, hiccups
- Oral bleeding, bloating sensation, dry mouth
- Erythema multiforme (a type of skin rash with red spots and sometimes blisters), acne, rash, dry skin
- Muscle pain, urinary tract pain
- Non-cardiac chest pain, pain
- Increased alkaline phosphatase levels
Not Known
Frequency cannot be estimated from available data
- Septic shock (life-threatening condition associated with blood poisoning)
- Secondary malignancy (new cancer caused by chemotherapy)
- Increased blood acidity
- Encephalopathy (abnormal brain function), extrapyramidal disorder (involuntary movements and rapid speech), fainting, paresthesia (crawling, tingling, or numbness)
- Dry eyes
- Heart failure, heart attack, pericardial effusion (fluid in the heart sac)
- Blood clots
- Sore throat, hoarseness, cough
- Gastrointestinal hemorrhage, colitis (colon inflammation), esophagitis, proctitis (rectal inflammation)
- Drug-induced liver damage, enlarged liver
- Dermatitis (skin inflammation), skin necrosis (dead skin tissue), skin ulcers, bronze discoloration of the skin
- Renal failure, hemorrhagic cystitis (bladder inflammation with bleeding), painful urination
- Increased lactate dehydrogenase levels (indicating tissue or cell damage)
Side Effects in Children and Adolescents
Children and adolescents may experience side effects that differ somewhat from those seen in adults. The following frequency classifications are specific to the pediatric population:
Very Common (Children)
May affect more than 1 in 10 patients
- Mucositis (inflammation of mucous membranes, particularly in the mouth, with ulcers)
- Diarrhea, nausea, vomiting, abdominal pain
- Liver damage
- Itching, hair loss
- Fever
- Increased levels of liver enzyme (ALT)
Common (Children)
May affect up to 1 in 10 patients
- Headache
- Sore throat, nosebleeds
- Difficulty swallowing, rectal inflammation, oral pain
- Exfoliative dermatitis (redness and scaling of a large area of skin), maculopapular rash, rash, skin redness, urticaria (hives), skin pain, bronze skin discoloration
- Chills
- Increased liver enzyme (AST) and bilirubin levels, increased C-reactive protein
Not Known (Children)
Frequency cannot be estimated from available data
- Secondary malignancy (new cancer caused by chemotherapy)
- Febrile neutropenia (low white blood cell count with fever)
- Electrolyte imbalances, decreased magnesium levels, decreased appetite
- Seizures, paresthesia (tingling or numbness)
- Eye hemorrhage, dry eyes
- Capillary leak syndrome, high or low blood pressure
- Hypoxia (reduced oxygen supply), cough
- Colitis, dyspepsia, rectal mucosal inflammation, gum pain, esophageal pain, constipation
- Enlarged liver
- Skin ulcers, erythema multiforme, bullous dermatitis (blistering skin condition), acne, hand-foot syndrome, diaper dermatitis with ulceration in the perianal area
- Pain in arms or legs
- Worsening kidney function, kidney failure, cystitis (bladder inflammation), blood in urine
- Scrotal redness, penile pain
- Facial edema, fatigue, pain
- Increased gamma-glutamyltransferase levels
It is important to report suspected side effects after the medicine has been authorized. This enables ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report any suspected adverse reactions through their national pharmacovigilance system. In the EU, reports can be submitted to the national competent authority. In the US, reports can be submitted to the FDA MedWatch program.
How Should You Store Trecondi?
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and carton after "EXP." The expiry date refers to the last day of that month.
No special storage conditions are required for the unopened vials of powder. The reconstituted solution has demonstrated chemical and physical stability for up to 3 days when stored at 25°C. From a microbiological perspective, the product should be used immediately unless the reconstitution method excludes the risk of microbial contamination.
Do not refrigerate (2°C-8°C) the reconstituted solution, as refrigeration may cause precipitation of the active substance. If precipitation is observed, the solution must not be used.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment. As a cytotoxic drug, Trecondi and all materials used for reconstitution and administration must be destroyed according to standard procedures for antineoplastic agents in compliance with applicable hazardous waste regulations.
What Does Trecondi Contain?
Trecondi has an unusually simple formulation: the active substance, treosulfan, is the only ingredient. There are no excipients, preservatives, or other additives in the powder formulation. This simplicity reflects the chemical properties of treosulfan, which can be formulated as a stable powder without the need for additional stabilizers.
Available Strengths and Packaging
- Trecondi 1 g: Each glass vial contains 1 g treosulfan as a white crystalline powder.
- Trecondi 5 g: Each glass vial contains 5 g treosulfan as a white crystalline powder.
After reconstitution with 0.45% sodium chloride solution (20 mL for the 1 g vial, 100 mL for the 5 g vial), each milliliter of solution contains 50 mg treosulfan. The reconstituted solution should appear as a clear, colorless solution. Any solution showing signs of precipitation must not be used.
The vials are made of Type I glass with rubber stoppers and aluminum caps. Trecondi is available in packs containing 1 or 5 vials. Not all pack sizes may be marketed in all countries.
Marketing authorization holder and manufacturer: medac Gesellschaft für klinische Spezialpräparate mbH, Theaterstr. 6, 22880 Wedel, Germany.
Frequently Asked Questions About Trecondi
Both treosulfan (Trecondi) and busulfan are alkylating agents used in conditioning regimens before stem cell transplantation. The pivotal MC-FludT.14/L clinical trial demonstrated that treosulfan-based conditioning was non-inferior to busulfan-based conditioning in terms of event-free survival. Some studies suggest treosulfan may have a more favorable toxicity profile, particularly regarding hepatic veno-occlusive disease and transplant-related mortality, though the choice between agents depends on the patient's specific clinical situation, the underlying disease, and institutional protocols.
The Trecondi conditioning regimen itself takes 3 consecutive days. Each infusion lasts approximately 2 hours. However, the complete conditioning process also includes fludarabine (and in children, usually thiotepa), which are given on a specific schedule determined by the transplant protocol. The conditioning phase is followed by a rest day and then the stem cell infusion. Recovery of blood counts typically begins 2-4 weeks after transplantation, and full immune reconstitution may take months to over a year.
No, Trecondi cannot be taken at home. It is an intravenous medication that must be administered in a hospital setting by healthcare professionals experienced in stem cell transplantation. The drug requires professional reconstitution and careful handling as a cytotoxic agent. Additionally, patients receiving myeloablative conditioning require continuous monitoring and access to supportive care measures including blood transfusions, antibiotics, and other emergency treatments.
After completing the Trecondi conditioning regimen, the donor stem cells are infused into the patient's bloodstream. Over the following weeks, the transplanted stem cells migrate to the bone marrow and begin producing new blood cells (engraftment). During this critical period, patients remain hospitalized and receive intensive supportive care including infection prophylaxis, blood product transfusions, and close monitoring for complications such as graft-versus-host disease (GvHD). Hospital stays typically last several weeks, and follow-up care continues for months to years after transplantation.
Trecondi received marketing authorization in the European Union in 2019. It is available in EU member states and several other countries that recognize EMA approvals. Availability may vary by country, and in some regions, treosulfan may be available under different brand names or through compassionate use programs. Patients should consult their transplant physician regarding the availability of treosulfan-based conditioning in their specific location.
After stem cell transplantation, your immune system needs time to rebuild. Live vaccines are contraindicated during treatment and for a prolonged period after transplantation. Inactivated vaccines can typically be restarted from around 3-6 months post-transplant, though the timing varies by vaccine and institutional protocol. Your transplant team will develop a personalized re-vaccination schedule based on your immune recovery. Complete re-vaccination is important because the new immune system from the donor does not retain immunity from your previous vaccinations.
References
- European Medicines Agency (EMA). Trecondi (treosulfan) - Summary of Product Characteristics. Last updated November 2023. Available from: EMA - Trecondi EPAR.
- Beelen DW, Trenschel R, Casper J, et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haematopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. The Lancet Haematology. 2020;7(1):e28-e39.
- Casper J, Holowiecki J, Trenschel R, et al. Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning. Bone Marrow Transplantation. 2012;47(12):1547-1553.
- European Society for Blood and Marrow Transplantation (EBMT). Handbook on Haematopoietic Stem Cell Transplantation. Updated 2024. Available from: EBMT.
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List (2023). Geneva: World Health Organization; 2023.
- Mohty M, Malard F, Abecasis M, et al. Revised definitions, grading and response criteria for hepatic sinusoidal obstruction syndrome/veno-occlusive disease in adult patients. Bone Marrow Transplantation. 2023;58(4):353-359.
- Slatter MA, Rao K, Amrolia P, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117(16):4367-4375.
Editorial Team
Medical Content
iMedic Medical Editorial Team - Specialists in Hematology and Clinical Pharmacology
Medical Review
iMedic Medical Review Board - Independent panel of medical experts
Evidence Standard
Level 1A - Based on systematic reviews and randomized controlled trials
Guidelines Followed
EMA SmPC, EBMT Guidelines, WHO Essential Medicines List, GRADE Framework
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