Clinical and Experimental Immunology ABSTRACTS doi:10.1111/cei.12741 UKPIN 2015 Meeting Abstracts December 2015 ORAL PRESENTATIONS O01 group and should be considered as an alternative thera- Excellent Outcome For Adults And Older Adolescents peutic option in PID patients not transplanted in child- Following Reduced Intensity Allogeneic hood where an appropriate donor is available. Triggers Haematopoietic Stem Cell Transplantation For for referral include life-threatening infections, malig- Inherited Primary Immune Deficiencies (PID). nancy and refractory disease. Emma Morris 1 ; Rachael Hough 2 ; Siobhan Burns 1 ; Ben Carpenter 2 ; Sarah Grace 3 ; Julia Dalhstrom 2 ; Kirsty O02 Thomson 2 ; Ronjon Chakraverty 4 Human IFNAR2 Deficiency: Lessons For Antiviral 1 Immunology, UCL Institute of Immunity and Transplantation; Immunity 2 Haematology, UCLH NHS FT; 3 Haematology, Royal Free Hospital Christopher Duncan 1 ; Siti Mohamad 1 ; Dan Young 2 ; NHS FT; 4 Haematology, UCL Cancer Institute Skelton 1 ; Leahy 3 ; Munday 2 ; Andrew Ronan Diane Karina Butler 3 ; Sofia Morfopoulou 4 ; Julianne Brown 5 ; Allo HSCT for adolescents and adults with PID has pre- Mike Hubank 4 ; Jeff Connell 6 ; Patrick Gavin 3 ; Cathy viously been avoided due to severe TRM and poor out- McMahon 3 ; Dempsey 7 ; Lynch 8 ; Eugene Niamh comes. We report the outcome of 34 consecutive Thomas Jacques 5 ; Manoj Valappil 9 ; Andrew Cant 1 ; patients undergoing RI Allo HSCT for PID, with a Karin Engelhardt 1 ; Judith Breuer 4 ; Richard Randall 2 ; median age of 22 years (range 12-50) at transplant. 24 Sophie Hambleton 1 were � 18 years at transplant. Diagnoses included X- 1 Newcastle 2 University 3 Our CGD (n 5 11), AR-CGD (n 5 3), variant CGD with University; of St Andrews; Lady’s Children’s Hospital; 4 University College London; 5 Great Ormond Street Crohn’s (n 5 1), CVID (one with T-NHL, one with 6 University College Dublin; 7 Cork University HLH) (n 5 4), autoimmune LPD (Fas mutation in one) Hospital for Children; 8 Bon Secours Hospital, Cork; 9 Public Heath (n 5 2), X-linked LPD (n 5 1), DCML deficiency (one Maternity Hospital; confirmed Gata2 mutation) (n 5 2), common gamma England Laboratory, Newcastle chain SCID (n 5 1), undefined SCID with atypical HL and DLBCL (n 5 1), NK deficiency (n 5 1), AR IL12rec Background : Type I interferon (IFN-1, IFN-alpha/beta) is beta deficiency (n 5 1), CD27 deficiency with HL and a fundamental antiviral defence mechanism. Mouse models DLBCL (n 5 1), XIAP with Crohn’s and HLH (n 5 1), have been pivotal to understanding the role of IFN-1 in Rag2 mutation with red cell aplasia (n 5 1). Also immunity, although validation of these findings in humans included were severe JIA (n 5 2) and refractory unclassi- has been limited. fied autoinflammatory syndrome (n 5 1). Donors were Aim : We investigated the molecular basis of viral suscepti- MUD (n 5 16), 1Ag MMUD (n 5 6), matched sibs bility in a previously healthy child with fatal encephalitis (n 5 11) and a 10/10 paternal donor. Stem cell source after inoculation of the live attenuated measles, mumps, was BM (n 5 10) or PBSC (n 5 24). RI conditioning regi- and rubella (MMR) vaccine. mens were Fludarabine, Melphalan, Alemtuzumab Methods : We employed targeted candidate gene resequenc- (n 5 21), Fludarabine, Bulsulphan, Alemtuzumab (n 5 9) ing, together with in vitro assays of interferon signaling or Fludarabine, Busulphan, ATG (n 5 4). With a median and response, and control of attenuated and wild-type viral follow up of 35 months (range: 2m to 10yrs 9m), the replication in primary fibroblasts. We used lentiviral trans- estimated overall survival is 91% at 1 year and 88% at duction to reconstitute patient cells. 3 years, with no deaths observed beyond 28m post- Results : We identified a homozygous null mutation in the transplant. Allo HSCT is well tolerated in this patient high-affinity IFN-alpha/beta receptor ( IFNAR2 ) in the C 2015 The Authors V 1 C 2015 British Society for Immunology, Clinical and Experimental Immunology V Clinical and Experimental Immunology, 182: 1–34
UKPIN 2015 POSTERS O04 proband, as well as a newborn sibling, that rendered cells Immunoglobulin Patient Evaluation Tool (IgPET) unresponsive to IFN-1. Reconstitution of the proband’s Emily Carne 1 ; Christine Symons 2 cells with wild-type IFNAR2 restored IFN-1 responsiveness and control of attenuated viruses. Despite the severe out- 1 Department of Immunology, Immunodeficiency Service for Wales, come of systemic live vaccine challenge, the proband had University Hospital of Wales; 2 Department of Immunology and Allergy, previously shown no evidence of heightened susceptibility Derriford Hospital to viral pathogens. Conclusions : This novel PID, IFNAR2 deficiency, supports Background : Current management of patients that require an essential but narrow role for IFN-1 in human antiviral immunoglobulin therapy is based on clinical judgement immunity. and expertise. To support healthcare professionals treating these patients, we propose a new Immunoglobulin Patient Evaluation Tool (IgPET) to assist assessment of patients’ O03 ongoing suitability for immunoglobulin treatment and Treatment Satisfaction Upon Switching To Flexibly- provide an audit trail for these decisions. Using a set of dosed Subcutaneous Immunoglobulin G In Primary auditable questions, based on patients’ lifestyle, circum- Immunodeficiency stances and diagnosis, this tool helps provide a standar- dised approach and addresses Key Performance Indicators Claire Jones; Sadia Noorani for the National Immunoglobulin Database to ensure con- Department of Immunology, Sandwell and West Birmingham Hospitals tinued immunoglobulin supply and patient care. NHS Trust Methods : IgPET is designed to capture a patient’s ability to self-administer immunoglobulin. Patient suitability for Background : Flexibly-dosed subcutaneous immunoglobu- home therapy is assessed by their treatment history, age, lin (SCIg) offers patients with primary immunodeficiency distance from home to treatment centre, ability/willingness (PID) the opportunity to schedule treatment around their to self-administer and personal support network. The most lives. Here we report on treatment satisfaction in patients suitable immunoglobulin administration method/fre- with PID who have switched from hospital-based intrave- quency is also considered by recording: patient’s immuno- nous immunoglobulin (IVIg) or home-based pump- globulin treatment status; feelings about infusing versus administered SCIg to flexibly-dosed SCIg. injecting; attitude towards using needles; confidence in Methods : Pre- and post-switch treatment satisfaction ques- infusion/injection technique; language/learning/manual tionnaires were completed by 4 patients with PID. IgG lev- dexterity/sight difficulties; infusion volume/multiple treat- els were monitored pre- and post-switch. ment site requirement; infusion frequency; known treat- Results : Pre-switch, IVIg-treated (every 3 weeks) patients ment adherence issues; practical problems or time issues were 100% satisfied with their treatment, reported infu- with set-up/infusion; and lifestyle. Guidance can then be sion durations of 150–240 minutes, side effects (head- given on each patient’s suitability for home therapy and the ache and tiredness) in 11–64% of infusions, benefit of method/frequency of immunoglobulin administration. treatment after 1–4 days and wear-off of benefit approx- Results and Conclusions : Once implemented, IgPET imately 2 weeks into their dosing cycle. Main reasons should be used periodically throughout the patient’s treat- for switching from IVIg were ‘convenience’ , ‘home- ment journey to support provision of individualised ther- therapy’ and ‘duration of infusion’. The patient originally apy; it should not replace professional judgement but on pump-administered SCIg switched to manual-push could aid training and decision making whilst capturing SCIg for time saving benefit. Post-switch, patients information for the purpose of clinical governance and remained 100% satisfied with their treatment with side audit. effects (mostly local) in 10–50% of infusions. In patients who switched to manual-push SCIg, infusion durations were 20 minutes (rated as ‘very convenient’), treatment O05 benefit was noticed 1 day after infusion and no wear-off Identification Of Heterozygous Single- And Multi- of treatment effect was reported. All patients remained exon Deletions In IL7R By Whole Exome Sequencing clinically stable; post-switch IgG levels were 9.8–11.9 g/ Karin R. Engelhardt 1 ; Yaobo Xu 2 ; Angela Grainger 1 ; L. Patients rated their switch training as ‘very good’, and Mila G.C. Germani Batacchi 1 ; David J. Swan 1 ; Joseph no patients wish to consider an alternative treatment D.P. Willet 1 ; Intan J. Abd Hamid 1 ; Philipp Agyeman 3 ; schedule. Dawn Barge 3 ; Shahnaz Bibi 4 ; Lucy Jenkins 4 ; Terry Conclusions : The switch to flexibly-dosed SCIg met all Flood 3 ; Mario Abinun 3 ; Mary Slatter 3 ; Andrew R. patients’ expectations: shorter infusion durations, fewer Gennery 3 ; Andrew J. Cant 3 ; Mauro Santibanez Koref 2 ; side effects, no wear-off of treatment benefit and the con- Sophie Hambleton 1 venience of home-based therapy. C 2015 The Authors 2 V C 2015 British Society for Immunology, Clinical and Experimental Immunology V Clinical and Experimental Immunology, 182: 1–34
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