Background:
Blood transfusions have long been associated with immunosuppression. The mechanism of transfusion-related immunomodulation remains elusive but is likely due to cell-mediated mechanisms that lead to decreased antigen presentation, T-cell ratios, and natural-killer cell functions. Recent literature studying the impact of blood transfusion on outcomes in patients with head and neck cancer (HNC) have shown that blood transfusions are associated with increased risk of death as well as higher wound infection rates. As such, the increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit has come into question. The purpose of this prospective study was to implement a lower transfusion threshold while comparing outcomes of free flap patients following the initiation of a new transfusion guideline.

Methods: A prospective study of all patients who underwent free tissue transfer after HNC resection between July 17, 2007 and June 7, 2021. Pertinent demographic and clinical data were collected. Our institution began implementing an updated transfusion criteria in 2014, as our Hematocrit threshold to transfuse was incrementally reduced from hematocrit <30 to <21 finally in 2017. A portion of patients in the transition group were excluded as criteria was adjusting. Our control group (group 1) represented patients before 2014, and patients after 2017 were included in the stricter transfusion criteria group (group 2).

The overall survival (OS) and recurrence free survival (RFS) of our two groups were determined using the Kaplan-Meier method and compared statistically using log-rank tests. Chi-square test and student t-test were used for analysis of the variables of each group.

Results: A total of 346 patients met the criteria for inclusion in the study. Group 1 consisted of 171 patients compared with 175 in group 2. The majority of patients had squamous cell carcinoma (84.4%), and the most common tumor site was the oral cavity (67.9%). Group 2 had a statistically significant higher rate of stage III/IV tumors (71.7% vs 60.5% in group 1, p=0.028). Mean length of stay was significantly shorter in group 2 (8.3days vs. 9.9 in group 1, p=0.001). Mean units of blood transfused per patient was significantly less in group 2 (0.26 vs 2.87 in group 1, p<0.001). Patients in group 2 also experienced significantly less postoperative wound breakdown or infections (14.3% vs. 26.3% in group 1, p=0.006). There was a difference between the types of flaps used in both groups, with group 1 having significantly more radial forearm free flaps whereas group 2 had an increased number of ALT flaps (p=0.006). Group 1 was associated with worse OS (p=0.01; hazard ratio [HR]=1.7) and RFS (p<0.001; HR=2.5). Comparing only patients with SCC between the two groups also found poorer OS and RFS in group 1 (p=0.002; HR=2.0) and RFS (p<0.001; HR=2.4). Free flap failure rates were the same in both groups (3.5% group 1 vs. 1.7% group 2; p=0.29).

Conclusion: After implementing a lower transfusion threshold of hematocrit <21 for HNC patients, we demonstrated an improvement in OS, RFS, and wound infection rates without any impact on free flap survival.