In the treatment of malignant lymphoma (ML), autologous hematopoietic stem cell transplantation (ASCT) is one of the important means, and high-dose chemotherapy combined with ASCT is considered to be the standard treatment for chemotherapy sensitive relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) patients \[1,2\]. Preconditioning is an important part of ASCT, which refers to high-dose chemotherapy and (or) radiotherapy and immunosuppressive treatment before hematopoietic stem cell transfusion to clear tumor cells in patients and prepare for hematopoietic stem cell transfusion \[3\]. With the development in recent decades, the preconditioning regimen has also undergone diversified changes. From the whole body irradiation (TBI)/cyclophosphamide (Cy) in the 1970s to the Mafran /Cy in the 1980s \[4\], various transplant centers have been trying various improved programs. The overall survival rate of different high-dose regimens combined with AHSCT is about 30-70% \[5\].
The simple chemotherapy transplantation preconditioning regimen without TBI can be divided into camustine (BCNU) and BU-based regimen. BCNU is one of the commonly used alkylating agents and is often combined with VP-16, Arc-C, Cy, Bu to form BEAM, CBV, BEAC and other transplantation preconditioning regimen. BEAM and CBV are the most commonly used solutions. The 5-year OS and 5-year PFS in the treatment of relapsed refractory lymphoma by ASCT with BEAM preconditioning regimen were 44%-71% and 35%-50% \[6,7\]. Compared with CBV, BuCy, and TBI, BEAM preconditioning showed better survival benefits in 3-year PFS and OS in non-Hodgkin lymphoma autologous transplantation \[8\].
Due to the high incidence of interstitial pneumonia in lymphoma patients who received a pre-treatment regimen containing high-dose carmostine, a BeEAM regimen (bendamustine, etoposide, cytarabine, mephalam) was replaced with carmostine to reduce toxicity and improve efficacy. Redondo AM et al. \[9\] reported the results of BeEAM protocol in DLBCL and peripheral T-cell lymphoma in a phase 2 clinical trial: the 3-year PFS and OS were 58% and 75%, respectively, the non-recurrent mortality was similar to that of previous pretreatment regimen, and the incidence of other toxics was lower. Therefore, BeEAM regimen may be a preconditioning regimen that can improve efficacy and reduce toxicity in patients with aggressive NHL. Although BeEAM regimen reduced the incidence of interstitial pneumonia caused by camustine, the adverse reaction caused by mafaran, myelosuppression, was dose-limited toxicity, mainly manifested as leukopenia, thrombocytopenia and anemia, followed by gastrointestinal reactions, including nausea and vomiting. In order to further improve the safety of BeEAM regimen, drugs with similar mechanism and less toxic side effects can be used to replace Mafaran to form a new pretreatment regimen.
Mitoxantrone (MTO) is an anthraquinone antibiotic antitumor agent. Its main mechanism of action is to insert deoxyribonucleic acid through hydrogen bonding, which causes the cross-linking and breaking of DNA structure. Can interfere with RNA; As a topoisomerase II inhibitor, mitoxantrone is a cell cycle non-specific drug that can kill both proliferative and non-proliferative cancer cells in humans \[10\]. Mitoxantrone injection was used in combination with cyclophosphamide, carazine, and podoside as a preconditioning regimen for autologous peripheral blood stem cell transplantation in a patient with recurrent and refractory Hodgkin's disease, and the transplantation was successful with only mild gastrointestinal reaction. Mitoxantrone injection and Mafaran combined to compare the application effect of BEAM in ASCT preconditioning of lymphoma patients, the results showed that the OS of the two groups was similar, and the PFS of CR patients showed no statistical difference between the two groups. Mitoxantrone injection was also compared with the Cy-fTBI regimen combined with bixiaoan and Mafaran when exploring the transplantation preconditioning regimen for patients with non-Hodgkin's lymphoma. There was no statistical difference in remission rate, DFS and OS indexes between the two groups. Mitoxantrone injection combined with bioxan and mafaran significantly improved transplant-related mortality.
The development of mitoxantrone into liposomes to improve the release and distribution of drugs and reduce the side effects of drugs is worthy of the application of mitoxantrone hydrochloride liposomes in the pretreatment of lymphoma patients for autologous transplantation based on the factors of evidence-based medicine, diagnosis and treatment norms, and taking into account the cost-benefit ratio. The purpose of this study was to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine in patients pretreated for lymphoma autologous hematopoietic stem cell transplantation.
