A systematic review of pharmacological and cell-based therapies for the treatment of lymphoedema (2010-2021).

Abstract

BACKGROUND\nLymphoedema describes accumulation of interstitial fluid resulting from lymphatic failure and can be of primary or secondary origin, and is estimated to affect 200 million people worldwide. Secondary lymphoedema is commonly due to damage of lymphatic vessels following surgical procedures. Treatments include compression bandaging and exercise regimes, but currently no pharmacological therapy has been approved. We aimed to perform a systematic review of randomised controlled trials (RCTs) investigating pharmacological and cell-based therapies for secondary lymphoedema.\n\n\nMETHODS\nWe searched the databases Medline, Embase and clinicaltrials.gov, from January 2010 to May 2021. Only RCTs investigating pharmacological and/or cell-based therapies for secondary lymphoedema were eligible for inclusion, and studies examining only active filarial infection were excluded. Two reviewers independently screened studies for eligibility.\n\n\nRESULTS\n8 RCTs were identified that met the inclusion criteria. Overall, studies were of poor quality with high risk of bias. Ketoprofen demonstrated promising improvements in skin thickness and tissue histopathology score. There was some evidence to suggest doxycycline may be beneficial in non-filarial secondary lymphoedema, and a single small RCT demonstrated selenium may also confer some benefit. Neither synbiotics nor platelet-rich plasma resulted in reduced lymphoedema volumes or symptom severity, and although bone marrow-derived stem cells resulted in improved symptom scores, no significant volume reduction was detected. Although positive results were demonstrated in trials investigating benzopyrones, previous meta-analyses cast doubt on their efficacy. No two studies assessed the same intervention so meta-analysis could not be performed.\n\n\nCONCLUSIONS\nAlthough some studies appear promising, there is currently insufficient evidence for any pharmacological or cell based therapy for the use in patients with secondary lymphoedema. Further, large high-quality RCTs are required before treatment recommendations can be made.