Abstract
The pathogenesis of immune cytopenias involves diverse processes including production, inhibition, and destruction of specific blood cell types mediated by antibodies and/or T cells. Classic examples of immune-mediated cytopenias are immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) as well as T cell-mediated idiopathic neutropenia and pure red cell aplasia. Both antibody and autoimmune T cell responses may often coexist, and assignment of the proper pathogenic importance, albeit difficult, is crucial for rational therapeutic approaches. Clonal processes such as T-cell large granular lymphocytic leukemia (T-LGL) or various B cell dyscrasias may also occur. While the results of splenectomy have been studied in individual conditions such as Evans syndrome (ES), AIN, and AIHA, the availability of new therapies and improvement of surgery outcomes have provided an impetus to update the older and smaller series.
We retrospectively reviewed a cohort of 339 adult patients who underwent splenectomy at the Cleveland Clinic Foundation between 2002-2020 (Fig.1A), for whom the main indication for the procedure was: ITP (n= 235), AIHA (n=68), ES (n=26) and AIN (n=10). Among these subtypes, there were 15 patients with an established diagnosis of T-LGL. Our aim was to determine the hematologic response of patients who receive splenectomy for immune cytopenia following treatment failure with conventional therapies and identify factors that were associated with responses.
Overall, the median age of the patients was 55 years (IQR:68-36), M:F ratio=0.98, with a median time from diagnosis to splenectomy of 11 months (IQR:31-3). Prior to the procedure, all patients had failed multiple lines of medical therapies (mode 1, range1-4). The median preoperative platelet count was 19 (IQR:44-5) x109/L, median preoperative hemoglobin (Hb) of 9 (IQR:10-8) g/dl and median preoperative ANC of 0.28 (IQR:1.19-0.23) x109/L.
A total of 306 patients underwent laparoscopic splenectomy, while 33 patients had an open approach. In 16 cases (5%), we recorded an intraoperative conversion from laparoscopic to open splenectomy. The mean spleen weight was 477 gr (SD±687). The average operative time was 2.3 hours, with four days median hospital length of stay (range:1-50). The overall rate of postoperative complications with 30-day readmissions was 0.1%, with no mortality. Of note is that up to 20% of the cases had a post-operative diagnosis that was discordant with the original indication for splenectomy. These discordant diagnoses included benign conditions such as Felty's syndrome (n=2), as well as hematologic malignancies such as mature B-cell neoplasm (28), T-cell lymphoma (n=8), NK-LGL (n=1), and T-LGL (n=15).
The overall response rate (ORR) to splenectomy was 74%, of which 86% complete response (CR) and 14% partial response (PR) with relapse occurring in 12% of cases. In the subset of thrombocytopenic patients, CR reached 69% of patients (P<.0001) as early as one week following the procedure. At 1-year, the mean platelet count was 246 (SD±170) x 109/L and relapse occurred in 13% of patients. Conversely, in anemic patients, a CR was observed only in 55% (P<.0001) within two weeks following splenectomy. At 1-year, the mean Hb level was 11.7 (SD±1.3) g/dl, with relapse occurring in 6% of patients. Comparatively, 80% of patients who underwent splenectomy for neutropenia responded at 26 weeks post-splenectomy with relapse in 10% of cases. In known and newly diagnosed patients with LGL (n=16), the response with regard to the cytopenia resulting in splenectomy indication was 81%. The response in Felty's syndrome was 100%. When analyzing predictors of response, failed pharmacologic therapies with either intravenous immunoglobulin (IVIg) or rituximab was predictive of non-response to splenectomy (Fig.1B). No significant differences in spleen weight between responders and non-responders were observed.
Our results show a significant and durable response to splenectomy in immune-mediated cytopenia of various etiologies refractory to conventional therapies indicating that, in selected patients, splenectomy remains a rational salvage treatment with a low complication rate.
Disclosures
Maciejewski:Apellis Pharmaceuticals: Consultancy; Alexion: Consultancy.
