The Transition from Childhood to Adulthood in Chronic Immune Thrombocytopenia Patients: Clinical Management and the Role of Splenectomy and Thrombopoietin Receptor Agonists in a Single Center Experience

Abstract Introduction. Children diagnosed with Immune thrombocytopenia (ITP) will develop a chronic disease (plt < 100 x 109/L lasting >12 months since the onset) in 20-30% of cases. The transition from ITP started in childhood to adulthood has been scarcely studied and no specific studies have been published Aims.To present the results of a single center retrospective survey on ITP pts diagnosed in childhood who were sent in an adult setting to continue the management Methods. Charts of ITP pts diagnosed in childhood (1-17 yrs) in our Pediatric Dept who developed a chronic disease, need at least one line of therapy and were sent to our adult ITP office from Jan 2013 to Feb 2018, were retrospectively reviewed. Demographic and clinical data were collected and outcome was assessed based on established guidelines Results. Our Pediatric Dept accounts for a mean of 37 newly ITP diagnosis/year in children aged 1-17 yrs, with 32.8% of pts developing a chronic disease. During the selected observation time, 60 pts was expected to become > 18 yrs old with a chronic ITP. Overall 28 pts (14 female) pts were sent to our Adult ITP office at pediatrician's discretion (46.6% of expected). Table 1 summarizes demographic and clinical characteristics of pts. Median age at ITP diagnosis was 9.5 yrs (12 moths to 17 yrs). Median age of pts coming to the adult ITP office was 21 yrs (18 to 37 yrs) and the reason they were sent for was the need to continue a pharmacological treatment in 8 cases (eltrombopag-Elt-), bleeding in 3 cases, pregnancy in 4 cases, plt count < 50 x 109/L in 13 cases. The median n of lines of treatment already received in childhood was 1 (1 to 4). 16 pts have received only steroid since diagnosis (on demand treatment for bleedings), 8 pts were treated with thrombopoietin receptor agonists (TPO-RA) and 1 also with rituximab. One patient, 8 yrs old, was splenectomized because of grade 3 multiple bleedings, with complete response (CR). He was sent to adult ITP office at 37 yrs when ITP relapsed, with grade 3 bleeding. Overall the median follow up from diagnosis, after the transition to adult ITP office is 18 yrs (4-39 yrs), the median n of lines at data cut-off was 2.5 (1-5) and the overall outcome is summarized in Fig 1. 11 patients were treated with TPO-RA (8 pts received Elt since childhood, 2 pts started Elt and 1 Rom in adulthood), ORR was 81.8% (CR=7). Since the transition 4 patients switched the TPO-RA because response to the first TPO-RA was suboptimal or minor side effect (headache) was reported or limited compliance was suspected. Splenectomy was offered to all patients treated with TPO-RA to avoid chronic pharmacological treatment, and to other selected patients with a low plt count and a history of bleeding. 8/11 patients accepted splenectomy. Median time since diagnosis to splenectomy was 8 yrs (1 to 18 yrs) and in all pts a stable CR (plt > 100 x 109/L) was achieved, with a median follow up after surgery of 36.5 months (10-48 months). Surgery was performed also in the previous splenectomized pt (29 yrs later) because an accessory spleen was detected, and a CR was achieved (follow up 40 months). 2 patients stopped TPO-RA on a personal decision, refused splenectomy or other treatments: their plt count is < 30 x 109/L without bleeding. 15 pts were on active follow up without therapy (median plt count 58 x 109/L) and without any bleeding. One patient is waiting for splenectomy, taking prednison. The 4 pregnant patients were treated with steroids and IVIG, had natural labour without adverse events and their babies had a normal plt count. After pregnancy one pt was treated with Elt for 1 year, then she refused treatment and splenectomy. All 4 women returned to a number of plts similar to pre-gestational count. In 1 pt a MYH9 related-disorder was confirm at 21 yrs. Overall a CR was achieved during TPO-RA treatment in 9/11 pts and 9/28 (32%) achieved a stable CR after splenectomy Conclusions. The transition from childhood to adulthood in chronic ITP pts leads clinicians to challenges related to growing age, especially in female pts approaching the fertility and pregnancy specific needs. However only a minority of children with ITP developed a chronic disease which required a prolonged treatment. TPO-RA seems to be effective and well tolerated but chronic administration has limited compliance. Splenectomy, even if performed in adulthood after many yrs since diagnosis, allows to achieve a stable CR sparing young adults from chronic pharmacological treatment. Disclosures Gambacorti-Passerini: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy.