Background Interstitial lymphocytic lung disease (ILLD), a recently recognized complication of primary immunodeficiencies (PID), is caused by immune dysregulation, abnormal bronchus-associated lymphoid tissue (BALT) hyperplasia, with subsequent progressive loss of pulmonary function. Various modes of standard immunosuppressive therapy for ILLD have been shown as only partially effective. Objectives To retrospectively evaluate the safety and efficacy of abatacept or rituximab in treatment of ILLD in children with PID. Methods 29 children (median age 11 years) with various forms of PID received one of the two therapy regimens predominantly based on the lesions’ immunohistopathology: children with prevalent B-cell lung infiltration received rituximab (n = 16), and those with predominantly T-cell infiltration received abatacept (n = 17). Clinical and radiological symptoms were assessed using a severity scale developed for the study. Results The targeted therapy with abatacept (A) or rituximab (R) enabled long-term control of clinical (A 3.4 ± 1.3 vs. 0.6 ± 0.1; R 2.8 ± 1 vs. 0.7 ± 0.05, p < 0.01) and radiological (A 18.4 ± 3.1 vs. 6.0 ± 2.0; R 30 ± 7.1 vs. 10 ± 1.7, p < 0.01) symptoms of ILLD in both groups and significantly improved patients’ quality of life, as measured by the total scale (TS) score of 57 ± 2.1 in treatment recipients vs. 31.2 ± 1.9 before therapy (p < 0.01). Conclusions ILLD histopathology should be considered when selecting treatment. Abatacept and rituximab are effective and safe in differential treatment of ILLD in children.

Background PSTPIP1-gene associated autoinflammatory diseases is a group of clinically diverse syndromes predominantly manifested by various skin conditions (pyoderma gangrenosum, acne, hidradenitis suppurativa, necrotizing fasciitis). Yet one of them – PAMI – manifests mainly with haematologic abnormalities and autoinflammation with or without purulent features, presenting diagnostic difficulties for treating physicians – mainly haematologists. PAMI treatment is also challenging as IL-1 inhibitors alleviate inflammatory symptoms but cytopenias usually require additional therapeutic agents. Methods We describe five PAMI patients from 3 families: (2 girls, 2 boys, and affected mother of two patients). c.748G>A(p.E250K) heterozygous mutation in PSTPIP1 was detected in all patients via targeted panel next generation sequencing and confirmed by Sanger sequencing. Results The median age of disease onset was 2 years (varied from at-birth onset to 7 years), the adult patient manifested at the age of 3. As described all patients manifested with cytopenias: thrombocytopenia in three, severe anaemia in five, neutropenia in three. All patients had elevated CRP and zinc levels, as previously described. Splenomegaly was noted in five, lymphadenopathy in one, colitis in one, severe arthritis in one (adult patient) and arthropathy in two patients. Mild pyodermia was noted only in one patient, two patients had skin vasculitis. One patient developed myelodisplastic syndrome and underwent successful hematopoietic stem cell transplantation (HSCT). All patients received various immunosuppression prior to diagnosis with partial effect. After PAMI diagnosis rituximab was effective in two out of three, tocilizumab in one out of two, high dose anakinra in one patient. The girl who underwent HSCT is currently well, with full donor chimerism. Conclusions Haematologists need to be aware of the PAMI phenotype and include it in the diagnostic algorithm. Treatment still remains challenging and requires further investigation in larger groups of patients. Disclosure of Interest None declared

Background Immunoglobulin G4-related disease (IgG4-RD) is a chronic systemic inflammatory condition with an unclear pathophysiology and IgG4-positive plasma cells infiltration of various organs and parts of the body. If untreated, the disease can lead to fibrosis and irreversible organ damage. IgG4-RD mostly has been described in adults, hence it is generally unknown among paediatricians. Objectives We conducted a retrospective analysis of clinical features and response to therapy of five patients (one female, four males, median age 13,6 years) with IgG4-related disease, treated in our Centre. Methods The diagnosis was confirmed by detection of lymphoplasmacytoid infiltration with >30% of cells expressing IgG4 in all, and elevated IgG4 serum concentration in 4 cases. Results Three patients had localised lesions (orbit, hip muscle, peripancreatic tissue, respectively), two – multi-organ disease with polylymphadenopathy, pulmonary, renal and hepatic foci, dacryoadenitis with oedema of the eyelids. Autoimmune thrombocytopenia (70 × 109/l), neutropenia (0,79 × 109/l) were present in one patient. Rituximab therapy was successful in 2 cases (one patient received monotherapy with rituximab, another one – Rituximab and Sirolimus). Two other patients received JAK inhibitor therapy (ruxolitinib) with good effect. No side effects were noted. One patient underwent surgery – the infiltration in the abdominal cavity was removed with positive effect without specific therapy. Conclusions IgG4-RD symptoms can be diverse and sometimes atypical, so dealing with this pathology requires physician’s awareness. Rituximab was effective in patients with multi-organ manifestations, and JAK inhibitor (Ruxolitinib) was effective in patients with mono-focal disease. Steroids are routinely used in IgG4-RD as a first line of treatment with significant side effects. We propose that alternative drugs could be used in IgG4-RD, especially in paediatric patients to achieve fast remission with significant morbidity. Disclosure of Interest None declared

We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated ( n =20) and haploidentical donors ( n =13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10 6 /kg of CD34+ and 20 × 10 3 /kg of αβ-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40–204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2–3 was 39 (26–60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18–50)%. Transplant-related mortality is 10(4–26)%. Event-free survival (EFS) is 60(43–76)% and overall survival (OS) is 67(50–84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48–84)% and OS−72(53–90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML