P1601: predicting the response to splenectomy in immune thrombocytopenia (itp): a multi-centric pilot study

Topic: 32. Platelet disorders Background: Primary immune thrombocytopenia (ITP) is an acquired disorder characterized by immune-mediated platelet destruction. The spleen is a major player as it orchestrates the immune system derangement and it represents the major site of autoantibody production. This is nicely backed up by evidence-based effectiveness of splenectomy, which offers the highest rates of durable response. In spite of being the most effective curative treatment, splenectomy currently represents a last resort after failure of all the medical armamentarium, understandably due to the unpredictable long-term outcome which does not outbalance the drawbacks of an irreversible surgical approach. In such a context, a better prediction of response may redefine the timing of splenectomy, greatly supporting the management of ITP patients. Preliminary observations from our group highlighted a possible relationship between splenectomy response and a combination of clinical-histological parameters. To address this in more detail, we expanded our original observations to a multi-centric Italian study. Aims: This study aimed to (i) investigate clinical-histological predictors of splenectomy response in ITP patients; (ii) provide an easy-to-use score to predict splenectomy response. Methods: This retrospective, multi-centric study considered a discovery (n=25) and a validation set (n=39) of adult ITP patients, who underwent splenectomy for refractory disease in three Italian referral centers for ITP (Padua and Bologna University Hospitals; San Bortolo Hospital of Vicenza). The inclusion criteria were set as follows: availability of clinical-laboratory data (age at diagnosis; autoimmune comorbidities; bleeding symptoms; pre-splenectomy therapies; platelet counts pre/post-splenectomy); availability of splenic samples for histological analysis; clinical follow-up ≥3 months. Response to splenectomy was assessed by IWG criteria. In the discovery set, variables even marginally associated with surgical outcome (p<0.1) were combined in a clinical score, following assessment of the best cut-off values by ROC analysis. The score was then applied to the validation set. Survival analyses were run with log-rank test and Kaplan-Meier curves. Differences were considered statistically significant for p-values <0.05. Results: In the discovery set, post-splenectomy ITP recurrence was significantly associated with age at diagnosis ≥50 years (p=0.03). A trend toward statistical significance was also noted with presence of autoimmune comorbidities and with steroid administration (≥0.5 mg/kg/day) in the days immediately before surgery (p=0.06). The combination of such variables into an integrated score (1 point for each factor) disclosed higher relapse rates in patients with scores ≥1 (Positive Predictive Value [PPV]: 50%; Negative Predictive Value [NPV]: 100%; 1-year relapse-free survival [RFS]: 53% vs 100% with score ≥1 vs score =0; median follow up: 68 months; p=0.02). These results were confirmed in the validation set (PPV: 55%; NPV: 82%; 1-year RFS: 54% vs 89% with score ≥1 vs score =0; median follow up: 56 months; p=0.01). Of note, some histological parameters (i.e. low T follicular helper cell density and marginal zone atrophy) identified a small subset of patients at high risk of early post-splenectomy recurrence. Summary/Conclusion: An integrated set of clinical parameters (age at diagnosis; autoimmune comorbidities; pre-splenectomy steroid dosage ≥0.5 mg/kg/day) may predict splenectomy response in ITP. Histological evaluation adds to the identification of patients at high-risk of post-splenectomy relapse.Keywords: ITP, Chronic ITP, Immune thrombocytopenia (ITP), Splenectomy