Outcomes of splenectomy in benign and malignant hematologic conditions in the immunotherapy era

Abstract Introduction Splenectomy is utilized in benign and malignant hematologic conditions such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, thalassemia, hereditary spherocytosis, leukemia, lymphoma, and other lymphoproliferative disorders. However, it carries risks like perioperative infections, bleeding, venous thromboembolism (VTE), pulmonary and cardiac events. The introduction of targeted immunomodulatory therapies like Janus kinase inhibitors (2011), Bruton tyrosine kinase inhibitors (2013), and Chimeric antigen receptor T-cell therapy (2017), reduced the use of splenectomy. However, a subset of refractory patients still require it. While splenectomy outcomes are studied, no publicationscompare complication rates in relation to the adoption of immunotherapies. We hypothesize that fewer patients undergo splenectomy for hematologic indications, and that those who do have a splenectomy experience better perioperative outcomes due to improved disease control with immunotherapies. Evaluating these trends can inform modifiable risks. Methods This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to review outcomes of splenectomy cases before and after the approval of immunotherapies for hematologic diseases. Group 1 (G1) is pre-immunotherapy data from 1/1/2012-12/31/2014 and Group 2 (G2) is post-immunotherapy data from 1/1/2021-12/31/2023. Adults (age ≥18 years) with a primary diagnosis of a benign or malignant hematologic condition were included. Those with age <18, trauma or non-hematologic primary indications, secondary hematologic diagnoses, preoperative sepsis, and concurrent major surgeries were excluded. Diagnoses were stratified as leukemia, lymphoma, or benign autoimmune conditions. Complication rates between G1 and G2 were compared using chi-square or Fisher's exact tests. Our primary outcomes are number of splenectomies performed and 30-day mortality. Secondary outcomes are complications categorized as infectious (septic shock, sepsis, urinary tract infection, superficial/deep/organ space surgical site infection), bleeding, VTE (stroke, pulmonary embolism, deep vein thrombosis), pulmonary (pneumonia, intubation/ventilation), cardiac (arrest, myocardial infarction), and return to operating room (OR). Results The cohort included 1551 splenectomy cases (G1: 1067; G2: 484). G1 had 288 malignant (55 leukemia; 233 lymphoma) and 779 autoimmune cases. G2 had 141 malignant (30 leukemia; 111 lymphoma) and 343 autoimmune cases. From G1 to G2, splenectomies decreased by 51.04% for malignancy (leukemia=45.45%; lymphoma=52.36%) and by 55.97% for benign conditions. Infection rates in leukemia cases increased significantly 17.6% (p=0.03) from G1 to G2, while there was no change in bleeding (p=0.09), VTE (p=0.61), pulmonary (p=0.94), or cardiac (p=0.65) events. Lymphoma cases had a significant 10.7% (p=0.04) decrease in bleeding from G1 to G2, while other complication rates were unchanged: infectious (p=0.98), VTE (p=0.35), pulmonary (p=0.11), cardiac (p=0.55). Combined leukemia and lymphoma cases showed 12.2% (p=0.01) reduction in bleeding. Autoimmune cases showed stable complication rates: infectious (p=0.34), bleeding (p=0.09), VTE (p=0.69), pulmonary (p=0.93), and cardiac (p=0.19)). No significant change in rate of return to OR (p= 0.99, 0.18, 0.33) or 30-day mortality (p= 0.66, 0.72, 0.64) was seen in the leukemia, lymphoma, or autoimmune subgroups, respectively. Conclusions Our analysis showed splenectomy rates for hematologic conditions significantly declined over time in G2 due to the FDA approval of immunotherapies. Perioperative bleeding rates decreased for lymphoma cases, while infectious complications increased in leukemia cases. No significant changes were observed in other complications or mortality rates. Although our findings cannot confirm causality, these trends may reflect improved disease control with immunotherapy. We acknowledge the limitation of NSQIP in linking therapy use to individual patient outcomes. G1 and G2 time periods corresponding to therapy availability served as proxy. Nevertheless, findings highlight notable decline in splenectomies for hematologic diseases and suggest immunotherapy may contribute to improved outcomes for those still requiring splenectomy. Future studies focused on patient-level and agent-specific data may better elucidate risk stratification and clinical optimization strategies.