Azin Alizadehasl
1 
, Bita Shahrami
2,3, Reza Rahbarghazi
4,5, Azam Yalameh Aliabadi
1, Seyedeh Fatemeh Hosseini Jebelli
1, Yasamin Afsari Zonooz
1, Hoda Hakimian
1, Farzaneh Fathi
6, Sara Forati
1* , Aysa Rezabakhsh
7* 1 Cardio-Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran
2 Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3 Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
7 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Cyclophosphamide-induced cardiotoxicity, associated with its toxic metabolite acrolein, is a significant concern and unresolved issue, especially when cyclophosphamide is administrated in high doses. However, cardiotoxicity following low-dose cyclophosphamide has been also documented, especially in post-hematopoietic stem cell transplantation (post-HSCT) settings. Despite the involvement of multiple signaling pathways in cyclophosphamide-induced cardiomyopathy, the exact underlying mechanisms remain to be fully elucidated. This review outlines the current challenges of cyclophosphamide therapy in HSCT recipients. In addition, the promising therapeutic approaches by targeting acrolein’s anti-angiogenic effect were thoroughly discussed to better manage post-HSCT cyclophosphamide-induced cardiotoxicity.