This is irreversible and leads to cell apoptosis.Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects of phosphoramide mustard and acrolein by converting aldophosphamide to carboxycyclophosphamide that does not give rise to the toxic metabolites phosphoramide mustard and acrolein. This is because carboxycyclophosphamide cannot undergo β-elimination (the carboxylate acts as an electron-donating group, nullifying the potential for transformation), preventing nitrogen mustard activation and subsequent alkylation.Cyclophosphamide induces beneficial immunomodulatory effects in adaptive immunotherapy. Suggested mechanisms include:
Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
Induction of T cell growth factors, such as type I IFNs, and/or
Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space niche.Thus, cyclophosphamide preconditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor immunity. History
As reported by O. M. Colvin in his study of the development of cyclophosphamide and its clinical applications,

Phosphoramide mustard, one of the principal toxic metabolites of cyclophosphamide, was synthesized and reported by Friedman and Seligman in 1954 …It was postulated that the presence of the phosphate bond to the nitrogen atom could inactivate the nitrogen mustard moiety, but the phosphate bond would be cleaved in gastric cancers and other tumors which had a high phosphamidase content.
Priapism
A relatively rare side effect associated with trazodone is priapism, likely due to its antagonism at α-adrenergic receptors. More than 200 cases have been reported, and the manufacturer estimated that the incidence of any abnormal erectile function is about one in 6,000 male patients treated with trazodone. The risk for this side effect appears to be greatest during the first month of treatment at low dosages (i.e. <150 mg/day). Early recognition of any abnormal erectile function is important, including prolonged or inappropriate erections, and should prompt discontinuation of trazodone treatment. Spontaneous orgasms have also been reported with trazodone in men.Clinical reports have described trazodone-associated psychosexual side effects in women as well, including increased libido, priapism of the clitoris, and spontaneous orgasms. Others
Rare cases of liver toxicity have been observed, possibly due to the formation of reactive metabolites.Elevated prolactin concentrations have been observed in people taking trazodone. They appear to be increased by around 1.5- to 2-fold.Studies on trazodone and cognitive function are mixed, with some finding improvement, others finding no change, and some finding impairment.Trazodone does not seem to worsen periodic limb movements during sleep.Trazodone is associated with increased risk of falls in older adults. It has also been associated with increased risk of hip fractures in older adults. Pregnancy and lactation
Sufficient data in humans are lacking. Use should be justified by the severity of the condition to be treated. Overdose
There are reported cases of high doses of trazodone precipitating serotonin syndrome.