Postoperative Complications Following Total Knee Arthroplasty in Patients with Chronic Lymphocytic Leukemia

Background/Objectives: Chronic lymphocytic leukemia (CLL), the most common leukemia in adults, predominantly affects the aging population. With improved survival from modern targeted therapies, a growing number of CLL patients are living long enough to become candidates for quality-of-life-improving procedures such as elective total knee arthroplasty (TKA). However, the impact of CLL on postoperative outcomes remains poorly understood. Methods: A retrospective cohort analysis was performed using the TriNetX Research Network. Adult patients who underwent primary TKA were identified and divided into two cohorts. CLL and non-CLL control, and 1:1 propensity score matching was performed on demographics and comorbidities. Medical complications were assessed at 30 and 90 days, and implant-related complications at 1 and 3 years postoperatively. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Within the CLL cohort, a Cox proportional hazards model was used to identify preoperative laboratory values, medications, and comorbid diagnoses associated with complication development. Results: After matching, 2054 patients, 1027 per cohort, were analyzed. Patients with CLL demonstrated significantly higher risks of postoperative pain at both 30 days (p < 0.001) and 90 days (p < 0.001), as well as transfusion (p = 0.035) and acute kidney injury (p = 0.036) at 90 days. At 1 year, the CLL cohort had elevated risks of periprosthetic joint infection (PJI; p = 0.015) and arthrofibrosis (p = 0.036), and these differences persisted at 3 years (PJI p = 0.033; arthrofibrosis p = 0.006). In the hazards model, preoperative hemoglobin < 8 g/dL (HR: 1.75, 95% CI: 1.27–2.41, p < 0.001), long-term anticoagulant or antiplatelet use (HR: 1.43, 95% CI: 1.13–1.80, p = 0.003), chronic kidney disease (CKD; HR: 1.28, 95% CI: 1.04–1.58, p = 0.021), and overweight/obesity (HR: 1.23, 95% CI: 1.00–1.50, p = 0.047) were independently associated with short-term complications. Chronic opioid use was found to be associated with an increased risk of long-term complications (HR: 2.80, 95% CI: 1.49–5.24, p = 0.001). Conclusions: Patients with CLL undergoing TKA had higher observed risks of both early medical and late implant-related complications. These findings may reflect the combined effects of CLL-related immune dysfunction, cytopenias, and chronic systemic inflammation, which may impair wound healing, reduce physiologic reserve, and blunt infection clearance. Identification of associated, modifiable preoperative risk factors—anemia, anticoagulant exposure, CKD, obesity, and chronic opioid use—may provide actionable targets for optimization and risk stratification.