Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively.Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 AE 9% and 28 AE 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 AE 11% and 58 AE 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.

Background: Acute graft-versus-host-disease (aGVHD) is one of the leading causes of non-relapse morbidity and mortality following allogeneic hematopoietic cell transplant (allo-HCT). Ruxolitinib (RUX) may be a viable option for patients with steroid-refractory (SR)-aGVHD but limited data currently exists. Methods: We performed retrospective chart review to identify patients treated with RUX for S-R-aGVHD 2015-2016 at our center. Primary aGVHD and overlap syndrome were included. Patients who received 14 days of RUX were considered evaluable for response assessment. A complete response (CR) was defined as the absence of any symptoms related to aGVHD. A partial response was defined as the improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ. Responses must have maintained for 21 days. Results: Thirty-six patients were included in the analysis. None were treated on prospective trials of RUX. Demographics are described in Table 1. The median time from allo-HCT to start of RUX was 83 days (range 34-741). The median time from steroid initiation to RUX imitation was 16.5 days (range 2-280) and the median number of prior therapies for S-R-aGVHD was 2 (range 0-5). The majority of patients (72%) were initiated on 5mg BID RUX; 25% were initiated on 10mg BID; 1 patient was initiated on 5mg daily. The median duration of RUX treatment was 21.5 days (range 1-560); 67% received at least 14 days of treatment and were evaluable for response. The overall response rate was 58% with 25% obtaining a CR. RUX was well tolerated; hematologic toxicity was generally mild and not dose limiting and there were no cases of treatment-related mortality. The majority of patients discontinued due to treatment failure or clinical deterioration. Four patients discontinued for toxicity and six for issues in obtaining RUX. Overall, the estimated median overall survival (OS) was 4.9 months (95% CI 2.7-7.0). Of those who were evaluable for response, the median OS was 7.4 months (95% CI UTQ-15.9) for responders compared to 0.9 months (95% CI 0.7-1.1) for nonresponders (p < 0.001). The rate of relapse of primary disease was 8%; one patient relapsed while on RUX and two within 6 months following discontinuation. Conclusion: In this population of high-risk, S-R-aGVHD, RUX is well tolerated and the ORR is 58% (95% CI 38%-78%) in patients receiving 14 days of treatment.

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Aim: To evaluate the incidence and outcome of secondary immune thrombocytopenia (ITP) in a large cohort of paediatric Spanish patients. Methods: A retrospective observational study was conducted in two paediatricUniversity hospitals in Spain between 2009 and 2019, which included children from 4 months to 18 years old diagnosed with ITP. Data were recorded from clinical charts: gender, age at diagnosis, coexisting condition and associated characteristics, outcome and treatment.Results: Secondary ITP was diagnosed in 87 out of 442 patients (19.6%). Postimmunisation ITP was seen in younger children. The onset of secondary ITP to autoimmune diseases (AD) and immunodeficiencies (ID) was at an older age and had more tendency to be insidious, and platelet level was higher than primary ITP. Mean time from ITP onset to AD diseases or ID diagnosis was 1.2 and 2.6 years, respectively. Whereas the cumulative incidence of remission was significantly higher in postimmunisation and post-viral infection (compared with primary ITP patients), it was worse in AD and ID patients.Conclusions: Identification of secondary ITP is important as it predicts outcome. Most of them are diagnosed at ITP onset, but AD diseases and ID should be ruled out periodically as they are usually identified later.

Background Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant‐associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. Methods This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). Results Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%‐91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%‐86%) and 62% (95% CI, 59%‐65%), respectively (P = .0015). With a longer follow‐up, median of 2 years (4 months–7 years), OS was 63% (95% CI, 59%‐67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%‐61%) and 26% (95% CI, 22%‐30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). Conclusions Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long‐term survival, as can be concluded from our study.