A highly popular alkylating agent is cyclophosphamide (CP) which has a major role in therapy of numerous malignancies as well as in immunosuppressive autoimmune conditions because of its strong cytotoxic and immunosuppressive effects. Although it is considered the most effective therapeutic agent, it is associated with a high risk of secondary malignancies related to therapy which is likely to occur with prolonged or massive exposure. The secondary malignancies, especially the hematological malignancies, such as therapy-related acute myeloid leukemia and myelodysplastic syndromes, and the solid tumours, such as bladder cancer, are significant health issues in the survivors in the long term. The current research will examine the molecular pathophysiology mediating CP-induced carcinogenesis and the epidemiology of secondary malignancies. The systematic and narrative review of the studies published in 2020-2025 was carried out to summarize the existing evidence. The major discoveries point to the importance of DNA alkylation, interstrand cross-linkage, oxidative stress, and epigenetic changes in the process of genomic instability and malignant transformation. Moreover, there is a well-established dose-response relationship and variable latency periods of the patients across populations of the patients. The epidemiological processes suggest that there is a growing incidence of secondary malignancies that are characterized by longer survival and exposure cumulative. This paper highlights the significance of risk stratification, early diagnosis and long-term monitoring interventions and the necessity of tailored therapeutic interventions to optimize the efficacy of treatment and manage the risk of carcinogens.
Shabnam et al. (Wed,) studied this question.