Antifungal prophylaxis in patients with haematological malignancies receiving chemotherapy or haematopoietic stem cell transplantation: a systematic review and network meta-analysis.

Purpose: To compare systemic antifungal prophylaxis for proven/probable invasive fungal disease (IFD) in high-risk haematology populations using randomised controlled trials, with separate mortality, discontinuation, and formulation analyses. Methods: Six databases and conference sources were searched to 2 September 2026. Bayesian random-effects network meta-analysis included RCTs with traceable proven/probable IFD definitions. Mixed-policy, setting, formulation, mortality, and discontinuation analyses were reported separately. PROSPERO: CRD420261490010 (retrospective). Results: Twenty-one RCTs (42 arms; 6,338 participants; 363 events) informed the primary network. Versus inactive control, voriconazole (OR 0.042, 95% CrI 0.001–0.793) and liposomal amphotericin B (OR 0.335, 95% CrI 0.127–0.819) had credible intervals excluding 1. Posaconazole suspension showed favourable but imprecise estimates. No mortality comparison demonstrated clear benefit (17 RCTs; 582 deaths). Exploratory peri-HSCT analyses suggested fewer IFDs but more discontinuations with itraconazole. In AML/MDS chemotherapy, posaconazole effects were comparator-dependent. Direct evidence did not distinguish delayed-release tablets from suspension. Conclusion: No regimen was consistently superior across settings and outcomes. Voriconazole and liposomal amphotericin B had the clearest evidence versus inactive control. Posaconazole effects were comparator-dependent; peri-HSCT itraconazole showed fewer IFDs but more discontinuations. No mortality benefit was established. Prophylaxis should be risk-adapted to clinical setting, baseline mould risk, formulation, tolerability, and feasibility.