thiotepa + busulfan + fludarabine

TBF is a myeloablative conditioning (MAC) regimen that combines three potent agents: 1. **Thiotepa** - An alkylating compound with immunosuppressive properties that can penetrate the blood-brain barrier, providing central nervous system protection with reduced non-hematologic toxicity[1][5]. 2. **Busulfan** - An alkylating agent that also penetrates the central nervous system, mimicking the effects of radiation therapy[1]. 3. **Fludarabine** - A purine analog with immunosuppressive properties that enhances the engraftment process[5]. This regimen was initially designed for cord blood transplantation in patients with active disease and was later widely adopted in Italy for haploidentical transplants[1]. TBF has demonstrated promising outcomes in various donor settings, including matched sibling donors (MSD), unrelated donors (URD), cord blood, and haploidentical transplants[2][5]. **Clinical Efficacy** Studies have shown that TBF provides significantly lower relapse rates compared to busulfan-fludarabine (BF) conditioning, particularly in patients with AML in first remission[2][5]. A retrospective study comparing TBF with busulfan-cyclophosphamide (BuCy) found that TBF was associated with a significantly lower relapse risk (HR 0.6, P=.02)[2]. However, TBF has been associated with higher non-relapse mortality (NRM) in some studies, which may offset its anti-leukemic benefits, resulting in similar overall survival rates compared to other regimens[5]. The higher NRM appears to be dose-dependent, with reduced busulfan doses (9.6 mg/kg vs. 12.8 mg/kg) showing more acceptable NRM profiles[5]. **Dosing** The standard TBF regimen typically includes: - Thiotepa: 10 mg/kg (total dose) - Busulfan: 9.6 mg/kg - Fludarabine: 150 mg/m²[1] **Applications** TBF has been studied in various hematological conditions: 1. **Acute Myeloid Leukemia (AML)** - Particularly effective in patients in first remission[2][5]. 2. **Myelofibrosis** - A single-center study reported favorable outcomes with no relapses observed at a median follow-up of 39 months[8]. 3. **Active Leukemia** - Although studied in this context, one report suggested that TBF does not improve outcomes in patients transplanted with active leukemia[1]. **Safety Profile** TBF is associated with a risk of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), particularly when compared to treosulfan-based regimens[7]. This should be considered when selecting conditioning regimens for patients at high risk of developing SOS/VOD. The regimen has also been associated with a trend toward higher risk of grades III-IV acute graft-versus-host disease (GVHD) but inferior chronic GVHD compared to BuCy[2]. Recent developments include the exploration of intensified conditioning approaches that combine busulfan, fludarabine, cladribine, venetoclax, and thiotepa for AML and MDS patients[3][10].

Other names

TBF