The choice of second‐line therapy in steroid‐resistant immune thrombocytopenia: Role of platelet kinetics in a single‐centre long‐term study

Abstract

*Splenectomy is a time-honoured well established approach for patients with steroid-resistant immune thrombocytopenia (ITP). However, due to the more recent availability of therapeutic options alternative to splenectomy, such as rituximab and agonists of the thrombopoietin-receptor, the choice of second-line therapy is challenging. Platelet kinetics has been widely used to predict response to splenectomy. We describe the outcome of 70 chronic ITP patients who performed a platelet kinetic study after failure of frontline corticosteroids and subsequently underwent open splenectomy. After a median follow-up from surgery of 20 years, 62 (88.5%) patients responded to splenectomy and 9 patients (13%) relapsed. Achieving a complete response (CR) significantly predicted a higher probability long-term stable response. The pattern of platelet sequestration was predominantly splenic in 52 patients (74%), predominantly hepatic in 12 patients (17%), and diffuse in 6 (9%). Patients with nonsplenic (diffuse and hepatic) sequestration showed significantly lower overall responses compared to patients with splenic captation (P 5 0.002). A nonsplenic sequestration significantly correlated with lower CR rate and, among CR patients, predicted an increased risk of relapse. Also, the probability of stable responses in nonsplenic uptake patients was substantially lower than in patients with splenic uptake (85% vs. 50%, P 5 0.0083). Platelet life span and platelet turnover did not correlate with response and relapse rate. Overall, splenic sequestration was able to predict not only a better quality, but also a higher durability of the responses. However, it should be enphasized that the response rate and duration of response even in patients with nonsplenic uptake were similar or even superior to those reported in patients treated with rituximab as first option.

Updated international consensus report on the investigation and management of primary immune thrombocytopenia

“…193 Indium-labeled autologous platelet scanning may be able to predict response to splenectomy but is not widely available. [198][199][200][201] OPEN VS LAPAROSCOPIC SPLENECTOMY. Laparoscopic splenectomy is associated with significantly shorter hospitalization, less intraoperative blood loss, and quicker resumption of oral diet compared with open splenectomy (evidence levels IIb-III).…”

Phase 1b trial of pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE‐013

“…Autologous 111 Indium-oxinate-labelled platelet sequestration study in patients with immune thrombocytopenia treated by thrombopoietin receptor-agonists An increasing number of patients treated with thrombopoietin receptor-agonists (TPO-Ras) for immune thrombocytopenia (ITP) are reluctant to undergo splenectomy mostly because of the irreversibility of the procedure and concerns about its long-term safety (Kojouri et al, 2004;Boyle et al, 2013;Thai et al, 2016). Isotopic assessment of the site of platelet destruction using autologous 111 Indium-oxinatelabelled platelet kinetic study might help to determine whether or not splenectomy is indicated in these patients (Najean et al, 1997;Sarpatwari et al, 2010;Palandri et al, 2014). The interpretation of the isotopic study results depends on the expertise in the labelling procedure and on the response criteria used (Navez et al, 2015 (Najean et al, 1997).…”

“…production is not sufficient to overcome the platelet destruction by the immune system. The role of platelet sequestration isotopic study as a predictive factor of short and long-term response to splenectomy has been challenged by divergent reports or reviews (Navez et al, 2015), whereas three large independent studies have found a significant association with between purely or predominantly splenic pattern of platelet sequestration (Najean et al, 1997;Sarpatwari et al, 2010;Palandri et al, 2014). The distribution pattern of platelet splenic sequestration was similar in patients receiving TPO-RAs and untreated patients.…”

State of the art – how I manage immune thrombocytopenia

“…In patients considering splenectomy, I refer them for an indium‐labelled ‐platelet sequestration scan. Patients with predominant splenic sequestration appear to have better responses (approximately 90%), compared to patients with mixed liver and spleen destruction who have a 40% chance of remission (Sarpatwari et al , ; Palandri et al , ).…”