Lymphatic Recovery and Clinical Implications in Hand Allotransplantation: Insights From Indocyanine Green Lymphangiography

Abstract

Introduction: Hand vascularized composite allotransplantation (VCA) is currently considered a promising reconstructive approach for selected hand amputees. The major limitation of hand VCA is its risk of rejection, which influences the long-term survival of the allograft. The lymphatic system plays a key role in inflammation, antigen presentation, and immune regulation, yet lymphatic regeneration following upper limb VCA is poorly understood. The correlation between donor-recipient lymphatic reconnection and the allograft recovery and rejection is not well understood. This study was designed to describe lymphatic drainage patterns following upper limb transplantation using indocyanine green lymphangiography (ICG-L) and to explore descriptive associations between these patterns and clinical graft status. Materials and methods: This single-center, descriptive case series included seven patients who underwent bilateral upper limb transplantation in the tertiary care facility. ICG-L was performed on one transplanted limb per patient at a single, randomly selected follow-up time point. Indocyanine green dye was injected intradermally at the first webspace, fourth webspace, and the ulnar aspect of the wrist on the flexor surface. The lymphatic flow was visualized using near-infrared fluorescence imaging. Lymphatic drainage patterns were assessed within the allograft, across the donor-recipient interface, and in the recipient limb, and were categorized as linear (normal) or non-linear (abnormal) using Yamamoto’s classification. Clinical data, including limb edema and biopsy-proven rejection episodes, were collected. All data were analyzed descriptively; no formal statistical correlation was performed. Results: ICG-L was performed with timing varied from three months to four years and two months post-transplant. No adverse reactions to indocyanine green were observed. Six patients had no clinical lymphedema, while one patient demonstrated persistent edema associated with chronic rejection. A total of 21 rejection episodes were documented. Limbs demonstrating linear lymphatic flow at the donor-recipient interface accounted for 12 rejection episodes, while limbs with non-linear flow accounted for nine episodes. Lymphatic continuity into the recipient limb was observed in all but one supracondylar-level transplant. Conclusion: Lymphatic regeneration occurs following upper limb VCA despite the absence of surgical lymphatic anastomosis. The observed lymphatic patterns may reflect the complex role of lymphatics in edema resolution and alloimmune responses. The findings in this study are exploratory, and they highlight the need for further research on lymphatic reconnection and its potential for improving allograft function and immunotolerance. Limitations include a small sample size and a lack of serial time-bound measurements.