Purpose: Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera (PV). Despite its overall good safety profile, its use also in relatively young patients raises an interest on its potential impact on spermatogenesis. To perform a systematic review of all published articles investigating fertility in male patients affected by SCD, ET, and PV and treated with HU. Two paradigmatic case reports of patients affected by PV and ET, respectively, have been also reported. Materials and Methods: PubMed, EMBASE, and Cochrane databases were queried for all the published studies indexed up to November 15th, 2022. A combination of the following keywords was used: “hydroxyurea,” “fertility,” “male,” “sperm,” “sickle cell anaemia,” “sickle cell disease,” “essential thrombocythemia,” “polycythaemia vera.” Results: Of 48 articles identified, 8 studies, involving 161 patients, were eligible for inclusion. Overall, the number of spermatogonia per round cross section of seminiferous tubule were decreased in patients with SCD compared to healthy males. HU treatment was always associated with a worsening of semen parameters, even up to azoospermia. Notably, treatment discontinuation was associated with an improvement of semen parameters and a trend toward normalization in the case of PV and ET, with a less clear amelioration in men with SCD. In both our patients with either PV or ET, HU discontinuation was associated with a significant improvement of spermatogenesis with successful spontaneous pregnancies. Conclusions Published evidence do not consistently report normalization of spermatogenesis after HU discontinuation in SCD cases. Conversely, the literature almost consistently reported an improvement of semen parameters at the discontinuation of HU therapy in PV and ET cases. Our real-life two cases confirmed those findings. The willing of fatherhood and the need for effective fertility treatment warrant further research to improve work-up management in men with hematological disorders.

Background: Generic formulations of imatinib mesylate have been introduced in Western Europe since 2017 to treat patients with chronic myeloid leukemia (CML). However, results on the safety and efficacy of generic formulations are contrasting. The aim of this study was to investigate the safety and efficacy of generic imatinib in CML patients treated in 12 Italian institutes. Methods: This is an observational, retro-prospective analysis of patients with CML for whom the treatment was switched from brand to generic imatinib. We analyzed and compared the variation in quantitative PCR values before and after the switch, and the proportion of patients who maintained molecular response after changing from brand to generic imatinib. Adverse events (AEs) were also evaluated. Results: Two hundred patients were enrolled. The median PCR value after the switch was reduced by 0.25 compared to the values before the switch. A significant difference was found between median PCR values before and after the switch in favor of generic imatinib (P = 0 .0 0 3 ). Molecular responses remained stable in 69.0%, improved in 25.5%, and worsened in 5.5% of patients. AEs were similar in the pre- and post-switch periods; however, a significant difference was found in favor of generic imatinib for muscular cramps (P ＜ 0.0001), periorbital edema (P =0.0028), edema of the limbs (P ＜0.0001), fatigue (P=0.0482), and diarrhea (P =0.0027). Conclusion Our data indicate that generic imatinib does not have deleterious effects on CML control and present an acceptable safety profile, similar or better than brand imatinib.