Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up

Abstract

Patients with breast cancer-related lymphedema (BCRL) have reduced quality of life and arm function. Current treatments are palliative, and treatments improving lymphedema are lacking. Preclinical studies have suggested that adipose-derived regenerative cells (ADRCs) can alleviate lymphedema. We, therefore, aimed to assess whether ADRCs can alleviate lymphedema in clinical reality with long-term follow-up. We treated 10 patients with BCRL using ADRCs and a scar-releasing lipotransfer to the axillary region, and all patients were followed 1, 3, 6, 12, and 48 months after treatment. The primary endpoint was change in arm volume. Secondary endpoints were safety, change in lymphedema symptoms, quality of life, lymphedema-associated cellulitis, and conservative treatment use. There was no significant decrease in BCRL volume after treatment. However, self-reported upper extremity disability and arm heaviness and tension improved. Six patients reduced their use of conservative BCRL treatment. Five patients felt that their BCRL had improved substantially, and four of these would redo the treatment. We did not observe any cases of locoregional breast cancer recurrence. In this phase I study with 4 years of follow-up, axillary delivered ADRCs and lipotransfer were safe and feasible and improved BCRL symptoms and upper extremity function. Randomized controlled trials are needed to confirm the results of this study.

Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema

“…This may explain the inconsistent treatment results observed after microsurgical and physiotherapeutic lymphedema treatments 25 – 29 . Regardless, future studies are needed to elucidate whether the excess amounts of volume, fat and lean mass can predict which patients are more likely to benefit from selective BCRL treatments 30 , 31 .…”

The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment

“…Treatment codes for physiotherapeutic lymphedema treatment were used to confirm the diagnosis of BCRL and were retrieved from all hospitals in the region of southern Denmark or outside hospitals from referred BCRL patients. Identified patients with BCRL were further evaluated clinically in our Plastic Surgery subunit for surgical lymphedema treatment for: (21) duration of BCRL, (22) severity of BCRL using multiple circumference measurements to estimate limb volume 29,30 , (23) clinical BCRL stage 31 and (24) current use of BCRL treatment. Incomplete or inconsistent information regarding BCRL diagnosis was supplemented by review of the electronic medical records.…”

Cell therapy as a treatment of secondary lymphedema: a systematic review and meta-analysis

“…Although no adverse effects related to cancer have been observed, the potential risk of cancer recurrence of using stem cells in the treatment of secondary lymphedema should be studied. A recently published Phase I study has found no evidence of breast cancer recurrence at 4-year follow up [ 58 ]. However, to further substantiate this relevant safety concern, a greater number of patients must be followed up longer-term in randomized clinical studies to formally rule out any contribution of stem cell transplants to cancer recurrence.…”