Early ReportAutologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis
Introduction
Autologous haemopoietic stem-cell transplantation (AHSCT) has been described as a possible treatment for patients with severe autoimmune disease such as systemic sclerosis, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus refractory to conventional treatment.1, 2, 3, 4, 5, 6 A consensus report on inclusion criteria, conditioning regimen, and manipulation of the graft for AHSCT in adults was jointly written by the European League Against Rheumatism and the European Group for Blood and Marrow Transplantation (EULAR/EBMT).4, 7 Although the overall prognosis for most children with chronic arthritis is good, in a small proportion of children with systemic or polyarticular juvenile chronic arthritis (JCA), the disease is refractory to combinations of non-steroidal anti-inflammatory drugs (NSAIDs) and immunosuppressive drugs such as methotrexate, cyclosporin, cyclophosphamide, and prednisone. Many of these children have severe joint destruction and adverse effects from long-term treatment with second-line antirheumatic drugs. These children may potentially benefit from therapy that suppresses the autoreactive T-cellular immunity and gives a normal immune competence de novo by the infusion of naïve T-cell precursors. We report 6–18 months' follow-up in the first four children with longstanding and severe JCA treated with AHSCT.
Section snippets
Patients
The first patient, a girl aged 6 years, had had severe systemic JCA since the age of 1 year. She presented with periods of spiking fever, a fine pink rash, hepatosplenomegaly, and a polyarthritis affecting wrists, metacarpophalangeal joints, elbows, knees, and ankles. On presentation, the haemoglobin concentration level was 5·3 mmol/L (8·5 g/dL), the platelet count was 470·109/L, and erythrocyte sedimentation rate (ESR) was persistently high (range 35–100 mm/h). Rheumatoid factor and
Results
NSAIDs were continued, methotrexate and cyclosporin were stopped before AHSCT, and prednisone was tapered and stopped two months after AHSCT. Neurophil recovery (>0·5·109/L) occurred 20–30 days after AHSCT and the platelet count reached 20·109/L after 15–28 (table 1). 2–5 months after AHSCT the numbers of circulating T cells were normal with normal in-vitro mitogenic responses at 3–5 months after AHSCT.
The evolution of the disease was followed by the factors described by Giannini and colleagues,
Discussion
The conditioning was well tolerated in all four patients and there was a substantial resolution of signs and symptoms of active disease after AHSCT. The rapid initial response may have been due to high-dose cyclophosphamide, but the duration of the remission suggests to us that it is a specific effect of the AHSCT. The delayed recovery of blood-cell numbers after HSCT, may be caused by the effect of an intensive pretreatment on a subnormal haematopoiesis, by the manipulation of the graft, or
References (25)
Autologous bone-marrow transplantation for rheumatoid arthritis
Lancet
(1997)- et al.
Treatment of systemic sclerosis with autologous haemopoietic stem cell transplantation
Lancet
(1997) - et al.
Early recurrence of persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation
Blood
(1996) - et al.
Reactivation of rheumatoid arthritis and development of leukocytoclastic vasculitis in a patient receiving granulocyte colony-stimulating factor for Felty's syndrome
Am J Med
(1995) Myelodysplastic syndrome after autologous transplantation for lymphoma: the price of progress?
Blood
(1994)- et al.
Autologous marrow progenitor transplantation for severe long-lasting systemic lupus erythematosus (SLE)
Bone Marrow Transplant
(1997) - et al.
Bone marrow transplantation in the treatment of autoimmune diseases
Br J Rheumatol
(1997) - et al.
Stem cell transplantation in autoimmune disease
J Rheumatol
(1995) - et al.
Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study
Bone Marrow Transplant
(1997) - et al.
Blood and marrow stem cell transplants in auto-immune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT)
Bone Marrow Transplant
(1997)
Effective purging of bone marrow by a combination of immunorosette depletion and complement lysis
Exp Hematol
Preliminary definition of improvement in juvenile arthritis
Arthritis Rheum
Cited by (136)
Update on research and clinical translation on specific clinical areas from biology to bedside: Unpacking the mysteries of juvenile idiopathic arthritis pathogenesis
2017, Best Practice and Research: Clinical RheumatologyCitation Excerpt :These insights and postregistration studies such as Pharmachild and the German Biker Registry, which show that TNF inhibitors seem to be rather safe [114], fuel the idea of using TNF blockade earlier in the disease course, instead of selecting it for patients who proved refractory to MTX. Since 1997, in a European collaboration (the European Bone Marrow transplantation working party), autologous stem cell transplantations (ASCTs) were performed for severe JIA resistant to therapy [115–118]. These patients were resistant to all therapeutic modalities at that time, with (a high risk for) considerable disease-associated damage, and were suffering from (severe) side effects of chronic therapy (for example, growth retardation due to long-term use of steroids).
Pharmacology
2015, Textbook of Pediatric RheumatologyUpdate on research and clinical translation on specific clinical areas: From bench to bedside: How insight in immune pathogenesis can lead to precision medicine of severe juvenile idiopathic arthritis
2014, Best Practice and Research: Clinical RheumatologyMesenchymal stromal cells for treatment of arthritis
2014, Best Practice and Research: Clinical RheumatologyPharmacology and drug therapy
2011, Textbook of Pediatric RheumatologyAutologous hematopoietic stem cell transplantation for childhood autoimmune disease
2010, Pediatric Clinics of North AmericaCitation Excerpt :Most of the experience regarding the effects and complications of HSCT comes from a pioneering clinical trial in children with severe JIA from the Netherlands. Following their initial report14 and based on the conclusions from the First Workshop on Autologous Stem Cell Transplantation in Rheumatic Diseases of Childhood (Utrecht, the Netherlands, May 1998),15 a multicenter trial of TCD auto-HSCT was initiated by the European Group for Blood and Marrow Transplantation (EBMT) Working Party, with defined guidelines and inclusion criteria.16 These criteria were refined during subsequent international American-European workshops.17,18