Sickle Cell Disease (SCD) is a chronic, hereditary hemoglobinopathy with high global prevalence and substantial morbidity. Recent years have seen significant progress in curative therapies and in strategies for managing acute and chronic complications, including perioperative care. This meta-analysis integrates current evidence to evaluate the efficacy of novel curative interventions and perioperative approaches.

To systematically synthesize data on: (1) Gene therapy and Hematopoietic Stem Cell Transplantation (HSCT) as curative modalities; (2) Perioperative management strategies and associated surgical outcomes; and (3) Additional advances in SCD care.

Fifty-three articles, including randomized trials, systematic reviews, observational studies, and expert consensus statements, were analyzed. Studies included adult and pediatric populations, focusing on curative treatments, surgical interventions, and complication control. Data were extracted on efficacy, safety, and outcome measures.

Evidence from phase I/II trials supports gene-addition and gene-editing approaches for inducing fetal hemoglobin or correcting the sickle mutation. Lovo-cel and Cas9-edited autologous CD34+ cells demonstrated high rates of transfusion independence and reduced vaso-occlusive crises. HSCT remains the only established cure, with both allogeneic and haploidentical donor protocols showing long-term survival benefits. Mobilization advances, including plerixafor optimization, improve feasibility. Across studies, mixed donor chimerism remains a relevant predictor of sustained remission. Perioperative Management and Surgical Outcomes Meta-analytic synthesis shows consistent benefit of preoperative transfusion in reducing postoperative complications, particularly acute chest syndrome, in procedures such as pediatric adenotonsillectomy and orthopedic surgeries. In orthopedic contexts ‒ especially THA for osteonecrosis ‒ SCD patients have higher complication rates, supporting tailored perioperative guidelines. Across surgical categories, risk reduction strategies significantly decrease perioperative morbidity. Other Advances in Management Pooled analyses indicate emerging efficacy of combination pharmacotherapies, although long-term data remain limited.

The aggregated evidence indicates a paradigm shift in SCD management, with curative strategies moving toward clinical applicability and increasingly effective perioperative care protocols reducing surgical risk. Gene therapy trials report sustained hematologic improvements, while HSCT outcomes are improving with broadened donor eligibility. Perioperative data emphasize transfusion optimization, multidisciplinary planning, and complication prevention as determinants of surgical success. These findings align with a global trend toward integrated, proactive disease management.

Meta-analytic synthesis confirms that gene therapy and HSCT represent viable curative options for SCD, while structured perioperative protocols markedly reduce surgical risk. The convergence of curative innovations, complication-specific strategies, and broader health system adaptation is redefining SCD prognosis, with sustained potential for improved survival and quality of life.