Abstract
Lymphedema describes the accumulation of interstitial fluid that results from lymphatic failure. Lymphedema can be of primary or secondary origin and has been estimated to affect 200 million people worldwide. Secondary lymphedema is commonly due to damage to the lymphatic vessels after surgical procedures. Treatments include compression bandaging and exercise regimens. However, at present, no pharmacologic therapy has been approved. We performed a systematic review of randomized controlled trials (RCTs) that had investigated pharmacologic and cell-based therapies for secondary lymphedema.
We searched the databases MEDLINE, Embase, and ClinicalTrials.gov from January 2010 to May 2021. Only RCTs that had investigated pharmacologic and/or cell-based therapies for secondary lymphedema were eligible for inclusion. Those studies that had examined only active filarial infection were excluded. Two of us (J.W., S.T.) independently screened the studies for eligibility.
We identified eight RCTs that met the inclusion criteria. Overall, the studies were of poor quality with a high risk of bias. Ketoprofen demonstrated promising improvements in skin thickness and tissue histopathologic scores. Some evidence was found to suggest that doxycycline might be beneficial for nonfilarial secondary lymphedema, and a single, small RCT demonstrated that selenium might also confer some benefit. Neither synbiotics nor platelet-rich plasma resulted in reduced lymphedema volumes or symptom severity. Also, 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 have cast doubt on their efficacy. No two studies assessed the same intervention; thus, we could not perform a meta-analysis.
Although the results from some studies appeared promising, the available evidence at present is insufficient for any pharmacologic or cell-based therapy for patients with secondary lymphedema. Furthermore, large, high-quality RCTs are required before treatment recommendations will be possible.