Prognostic utility of myocardial work indices and biomarkers for identifying anthraquinone induced cardiotoxicity in hematopoietic stem cell transplantation

Abstract

Abstract High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (auto-HSCT) remains a critical treatment modality for lymphoma. While anthracycline-based regimens are foundational in lymphoma therapy, their cardiotoxicity often precludes use in auto-HSCT. Our prior research established the tolerability and survival benefits of mitoxantrone-based conditioning regimen over BEAM in lymphoma patients undergoing auto-HSCT. Although liposomal mitoxantrone is hypothesized to exhibit reduced cardiotoxicity, comparative studies evaluating its safety and efficacy in auto-HSCT settings are scarce. We initially compared cardiotoxicity biomarkers (CK-MB, LDH) and cardiomyocyte pathology in pre-clinical study, treated with mitoxantrone versus liposomal mitoxantrone in mice at human HSCT-equivalent doses. Liposomal mitoxantrone demonstrated significantly reduced cardiotoxicity. Subsequently, we conducted a prospective clinical trial (ChiCTR2500099269) from July 2022 to July 2025, comparing cardiotoxicity and efficacy between mitoxantrone (60 mg/m², n=29) and liposomal mitoxantrone (60 mg/m², n=28) as conditioning regimens for auto-HSCT. Patients underwent comprehensive assessment at baseline and 4 weeks post-chemotherapy using 3D echocardiography-derived myocardial work indices and biomarkers (Troponin T, CK-MB, BNP, LDH) to predict chemotherapy-related cardiotoxicity.The liposomal mitoxantrone group exhibited significantly lower cardiotoxicity biomarker fluctuation. Logistic regression analysis identified GLS decrease> 10%, LDH, TnT elevated after auto-HSCT as the strongest independent predictors of chemotherapy-induced cardiotoxicity. Both regimens demonstrated comparable efficacy in auto-HSCT. Three patients in the mitoxantrone group developed heart failure or severe atrial fibrillation after HSCT, whereas no events occurred in the liposomal group. Liposomal mitoxantrone shows promising potential for auto-HSCT conditioning. Myocardial work indices and specific biomarkers GLS could be integrated into clinical protocols for early detection and intervention of cardiovascular complications during chemotherapy.