Passenger lymphocyte syndrome following organ and stem cell transplantation: current insights and clinical implications

Background Passenger lymphocyte syndrome (PLS) is an alloimmune complication of ABO-mismatched solid organ or hematopoietic stem cell transplantation characterized by the production of antibodies by donor-derived B lymphocytes against the recipient’s red blood cell antigens. Its incidence, risk factors, and management remain poorly defined because many cases are subclinical, and most reports are case based. This study aimed to summarize the available literature on PLS, focusing on its incidence, immunohematologic mechanisms, clinical features, and management. Methods We systematically searched PubMed and Embase for publications up to August 2025 and included case reports, case series, and cohort studies describing PLS after kidney, liver, lung, intestinal, and hematopoietic stem cell transplantation. Data on epidemiology, ABO constellation, antibody specificity, clinical presentation, treatment, and outcomes were extracted. Results We identified 64 studies reporting 135 cases of PLS. All were observational comprising 78% case reports/series and 22% retrospective cohort. 17 studies involved kidney transplantation, 23 liver, 7 lung, 6 intestinal, 1 heart, and 10 hematopoietic stem cell transplantations. The reported incidence ranged from approximately 9% in kidney to approximately 30–40% in liver and over 50% in lung transplantation. ABO isoagglutinins were the predominant antibodies, while Rh, Kidd, Kell, and Lewis specificities were also implicated. Most cases presented within 1–3 weeks post-transplant with abrupt hemolysis, which was usually self-limiting; however, severe cases required transfusion support, plasma exchange, or rituximab. Mortality was rare but occurred in delayed or fulminant cases. Conclusions PLS is an under-recognized post-transplant complication with variable incidence and outcomes across organ types. Standardized diagnostic criteria, evidence-based management strategies, and multicenter studies are needed to guide clinical practice and improve patient outcomes.