25 Allogeneic Haematopoietic Stem Cell Transplantation for Systemic Onset Juvenile Idiopathic Arthiritis

Track: BMT Tandem "Scientific" Meeting
Thursday, February 12, 2015, 4:45 PM-6:45 PM
Seaport Ballroom ABC (Manchester Grand Hyatt)
Juliana Silva, MD , Blood and Marrow Transplantation Program, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
Julie Glanville , Blood and Marrow Transplantation Program, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
Fani Ladomenou , Department of Bone Marrow Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom
Rachael Hough , University College Hospital London, London, United Kingdom
Ben Carpenter , University College Hospital London, London, United Kingdom
Vicky Grandage , University College Hospital London, London, United Kingdom
Kanchan Rao, MD, MRCPCH , Blood and Marrow Transplantation Program, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
Persis Amrolia, MD, PhD , Blood and Marrow Transplantation Program, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom
Robert Chiesa, MD, PhD , Great Ormond Street Hospital for Children, London, United Kingdom
Paul Brogan , Rheumatology Department, Great Ormond Street Hospital, London, United Kingdom
Mark Friswell , Great North Children's Hospital, Newcastle upon Tyne, United Kingdom
Andrew J Cant, MD , Department of Paediatrics Immunology, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom
Zohreh Nademi, Dr , Department of Bone Marrow Transplantation, Great North Children's Hospital, Newcastle, United Kingdom
Mary Slatter, MD , Great North Children's Hospital, Newcastle, United Kingdom
Mario Abinun , Child Health Department, Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom
Paul Veys, MBBS , Great Ormond Street Hospital for Children, London, United Kingdom

Background: Some patients with systemic Juvenile Idiopathic Arthritis (sJIA) experience a severe disease course with destructive arthritis which is refractory to conventional therapy including the ‘biologics', and/or develop life threatening complications such as macrophage activation syndrome (MAS). This group of patients has been considered for allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the outcome of patients undergoing allogeneic HSCT for sJIA.

Methods: 8 patients (4 female) with sJIA underwent allogeneic HSCT at 3 UK transplant centers between 2007 and 2014. All patients were refractory to standard therapy (n=4), had failed autologous HSCT (n=1), or developed secondary HLH/MAS poorly responsive to treatment (n=3). Median age at transplant was 8.9 years (range 2 - 16 years). All received reduced toxicity conditioning regimens: Fludarabine, Melphalan, Alemtuzumab (n=6) or Treosulfan, Fludarabine, Alemtuzumab (n=2). All patients received peripheral blood stem cell grafts: from a 10/10 HLA matched unrelated donors (n=5), 9/10 HLA mismatched unrelated donors (n=2) and  matched sibling (n=1). Patients received Cyclosporin (CsA) and mycophenolate mofetil (MMF) for graft-vs-host disease (GVHD) prophylaxis (n=5), CsA alone (n=2) and 1 patient received Sirolimus and MMF due to previous CsA toxicity.

Results: Seven out of 8 patients are alive with median follow-up of 16 months (range 4 - 56 months); one patient who had a previous unsuccessful autologous HSCT died of severe metabolic acidosis and hyperglycaemia following an orthopedic procedure 20 months post successful mismatched unrelated donor HSCT. Four patients achieved full donor chimerism in all cell lineages and 4 (including both those who received Treosulfan-based conditioning) achieved high levels of mixed donor chimerism in all lineages. One patient had grade II and 1 patient had grade IV acute GVHD. With the use of Alemtuzumab in already heavily immunosuppressed patients, viral reactivation was observed in most, some with a more severe disease course (BK encephalitis; HHV6 enterocolitis). All patients had significant improvement of arthritis (Fig1), reduction of ESR (Fig2), resolution of MAS and improved quality of life following allogeneic HSCT; all achieved complete drug-free remission of JIA at last follow-up.

Conclusion: Allogeneic HSCT using Alemtuzumab and reduced toxicity conditioning appears to be an effective therapeutic option for patients with systemic onset JIA which is refractory to conventional therapy and/or complicated by MAS. Long term follow up is required to ascertain whether disease control continues indefinitely.

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Disclosures:
P. Veys, Astellas, none: Honoraria
Gilead, none: Advisory Board
Pfizer, none: Honoraria
EUSA, none: Advisory Board