HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) vs. ADIPOSE-TISSUE-BASED THERAPY AS A THERAPEUTIC OPTION IN SYSTEMIC SCLEROSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS Introduction: Systemic sclerosis (SSc) is a multisystem autoimmune disease. Currently, there is no cure for this disease. One of the emerging therapies for SSc includes hematopoietic stem cell transplantation (HSCT) and adipose-tissue-based therapy. A study that compares the usage of HSCT with adipose-tissue-based therapy in SSc has not been made. The objective of this study was to conduct a systematic review and meta-analysis that compared the efficacy of HSCT and adipose-tissue-based therapy in SSc. Methods: A comprehensive literature search was conducted from inception to 14th June 2023 in PubMed, CENTRAL, EBSCOhost, ProQuest, SAGE, and JSTOR. The inclusion criteria are: (1) Investigated the effects of HSCT or adipose-tissue-based therapy in SSc; (2) Study design is RCT; (3) Is a human study; (4) Written in English; (5) Full-text is available. The quality of evidence was assessed using Cochrane risk of bias 2 (RoB 2). Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). The outcomes are mean change in modified Rodnan skin score (mRSS), visual analog scale (VAS), quality of life (QoL), activities of daily living (ADL), and adverse events (AEs). Results: A total of 1011 articles were obtained after duplicate removal with 32 retrieved for a second screening and nine assessed for eligibility. Five articles were included in the systematic review and four in the meta-analysis. Overall, our study found 170 patients in the intervention group and 158 controls. There was a more significant change in the mean mRSS in those who received HSCT compared to adipose-tissue-based therapy (P < 0.00001). HSCT had significantly more SAEs compared to adipose-tissue-based therapy (P = 0.04). Two out of three HSCT studies reported two deaths in the HSCT group compared to no deaths in control. In contrast, there was no event of death in both the adipose-tissue-based therapy and control groups. There was a moderate risk of bias for our study and a moderate level of confidence. Conclusion: In conclusion, this meta-analysis suggested that HSCT might be superior to adipose-tissue-based therapy as therapy in SSc patients. Some of the limitations of our studies are the small number of studies, exclusion of non-English studies, and lack of studies that directly compared HSCT against adipose-tissue-based therapy. Thus, we strongly suggest more research regarding HSCT and adipose-tissue-based therapy in SSc patients to be conducted.