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Cyclophosphamide + Fludarabine + Thiotepa

Development stage
Unknown
Lead developer
Takeda
Modality
DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules
Administration
Intravenous
01

Overview

The combination of cyclophosphamide, fludarabine, and thiotepa is a conditioning regimen used primarily in allogeneic stem cell transplantation. This regimen is classified as reduced intensity conditioning (RIC) but remains functionally myeloablative, as evidenced by delayed neutrophil recovery and high donor chimerism[3]. ## Conditioning Protocol The standard dosing protocol for this combination typically includes: - Cyclophosphamide: 50 mg/kg (administered on day -6) - Fludarabine: 30 mg/m²/day for 5 days (days -6 to -2), totaling 150 mg/m² - Thiotepa: 5 mg/kg/day for 2 days (days -5, -4), totaling 10 mg/kg[3] This regimen is often combined with low-dose total body irradiation (TBI) of 400 cGy to enhance engraftment while reducing toxicity compared to high-dose myeloablative conditioning[3]. ## Clinical Applications This combination is primarily used in: 1. **Allogeneic stem cell transplantation**: Particularly for patients with acute leukemia or myelodysplasia[3] 2. **Cord blood transplantation**: The regimen has shown high rates of sustained neutrophil and platelet engraftment in double-unit cord blood transplants[3] ## Efficacy and Outcomes Research has demonstrated that this conditioning regimen: - Induces a high incidence of sustained donor engraftment without anti-thymocyte globulin (ATG)[3] - Functions as a reduced intensity but functionally myeloablative regimen - Achieves median day 21 total donor chimerism of 100%[3] - Differs from non-myeloablative conditioning by avoiding transient autologous recovery and initial mixed chimerism[3] ## Side Effects and Toxicity Profile Common side effects include: - Hair loss (alopecia) - Cognitive impairment ("chemo brain") - Gum enlargement - Skin color changes - Potential for delayed lung problems[6] Patients receiving this regimen require close monitoring with regular blood tests, sometimes daily, and treatment is typically administered through a central venous access device (CVAD)[6]. ## Comparison to Other Regimens When compared to other conditioning protocols: - It represents an alternative to both high-dose myeloablative and non-myeloablative conditioning[3] - Other centers have investigated similar reduced intensity regimens including Melphalan/Fludarabine, Melphalan/Thiotepa/Fludarabine, and Treosulfan/Fludarabine/TBI[3] This combination offers a balanced approach that aims to reduce regimen-related toxicity while maintaining sufficient immunosuppression and anti-leukemic activity for successful transplantation.

Other names
fludarabine/cyclophosphamide/thiotepafludarabine, cyclophosphamide, thiotepaFCT
02

Targets

DNARNR (Ribonucleotide reductase)

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