Intense immunosuppression followed by purified blood CD34+ cell autografting in a patient with refractory juvenile rheumatoid arthritis

Abstract

Summary:A 15-year-old boy with refractory juvenile rheumatoid arthritis (JRA) underwent intense immunosuppressive therapy followed by purified blood CD34+ cell autografting. He had been taking prednisolone (PDN) daily or every other day combined with methotrexate once a week to control the disease for 7 years. He suffered from psychological complications and a very short stature due to the adverse effects of these drugs. CD34+ cells were purified in bulk from G-CSF-mobilized PBSC using an Isolex 300. After the administration of cyclophosphamide (200 mg/kg) and anti-lymphocyte globulin (45 mg/kg), 3.6 × 10 6 /kg purified CD34 + cells were infused. His post-transplant course was uneventful except for herpes-zoster infection. He is now more than 1 year post transplant and has not taken any immunosuppressive medication. His rate of growth has increased (Ͼ10 cm/year) due to the effects of the cessation of PDN and the administration of recombinant human growth hormone (rGH), in contrast to the gain of 2 cm in the preceding 3 years with rGH treatment. Although the durability of this remission is unknown, intense immunosuppressive therapy followed by purified blood CD34+ cell autografting might be acceptable for adolescent patients with refractory JRA to achieve a drug-free period for physical and psychological maturation. Bone Marrow Transplantation (2001) 27, 333-336. Keywords: juvenile rheumatoid arthritis; growth retardation; purified blood CD34 + cell autografting; recombinant human growth hormone Juvenile rheumatoid arthritis (JRA) is one of the most common rheumatic diseases of children and a major cause of chronic disability.1-3 Although JRA is not always fatal, except in a small proportion of patients with systemic disease, it often becomes refractory to combinations of non- steroidal anti-inflammatory drugs (NSAIDs) or immunosuppressive drugs such as methotrexate (MTX), cyclophosphamide (CY), and corticosteroids. In such cases, patients are susceptible to severe joint destruction and various adverse effects from long-term treatment, and adolescent patients often must endure a mental and physical burden. To improve the quality of life in these patients, a new strategy with intense immunosuppression followed by stem cell support has been introduced, first for patients with fatal autoimmune disease, and then for those with non-fatal disease that is refractory to ordinary therapies. [4][5][6][7] We report here a 15 year-old boy with refractory JRA who was treated with high-dose CY and anti-lymphocyte globulin (ALG) followed by purified blood CD34 + cell autografting. Case reportThe patient was a 15-year-old boy. In October 1992, at the age of 8, he developed high-grade fever and multiple arthralgia. Since his symptoms failed to respond to antibiotics prescribed by a general practitioner, he was referred to the Department of Pediatrics of Tokushima Municipal Hospital. The laboratory examinations revealed acceleration of the erythrocyte sedimentation rate (102 mm/h) and elevation of C-reactive protein (14.5 mg/dl) a...

Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity

“…18 19 Since 1997, ASCT has been applied as an experimental procedure in a substantial group of children with refractory polyarticular and systemic JIA. [20][21][22][23] The majority of these patients (n = 41) can be identified in the registry of the EBMT. Recently we published a short report on the general outcome of 31 of these children.…”

Haematopoietic stem cell transplantation in paediatric rheumatic disease

“…In the longer term, improvement in the quality of life (QOL) and the ‘catch-up’ growth were significant, although the established tissue and organ damage sustained pretransplant were not reversible. For the JIA cohort, a complete, drug-free remission (CR) lasting up to 20 years was achieved by 55% (31/57), partial remission (PR) by a further 11% (6/57), but disease relapsed in 23% (13/57), including in two patients after 7 and 9 years of CR indicating the transient nature of the benefit at least for some patients, and seven patients died resulting in TRM of 12% (7/57) [18,19,28–42] (P. Veys, A. Lazareva, M. Slatter, personal communications). Of the 30 patients transplanted for other paediatric rheumatic diseases 70% (21/30) achieved long-term (up to 7 years) CR and further 10% PR, in 20% (6/30) disease relapsed, and one patient with JDM who achieved the only PR died [18,37,42–61] (P. Veys, T. Cole, D. Hughes, personal communication).…”

“…Autologous T cell depleted HSCT for paediatric rheumatic diseases transient nature of the benefit at least for some patients, and seven patients died resulting in TRM of 12% (7/57)[18,19,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] (P. Veys, A. Lazareva, M. Slatter, personal communications). Of the 30 patients transplanted for other paediatric rheumatic diseases 70% (21/30) achieved long-term (up to 7 years) CR and further 10% PR, in 20% (6/30) disease relapsed, and one patient with JDM who achieved the only PR died[18,37,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] (P. Veys, T. Cole, D. Hughes, personal communication).…”

Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders

“…McColl 1999 [28] RA (6) 5 PR alive Pavletic 2001 [29] RA (6) 6 PR alive Bingham 2001 [30] RA (14, 12 transplanted) 8 PR alive Verburg 2001 [31] RA (1) PR alive Kim 2002 [32] RA (33) 23 PR alive Moore 2002 [33] AOSD (1) remission alive Lanza 2000 [34] JIA (4) 4/4 remission alive Wulffraat 1999 [35] JIA (1) NA died Quartier 1999 [36] JIA (1) remission alive Nakagawa 2001 [37] SSc (1) remission alive Tyndall 1997 [38] SSc (1) remission alive Martini 1999 [39] SSc ( [49] MCTD (1) PR alive Myllykangas 2000 [50] PM (1) remission alive Baron 2000 [51] PM (1) PR alive Bingham 2001 [52] MS (3) 3/3 PR alive Burt 1998 [53] MS (24) 18/23 PR 1 died Fassas 2000 [54] MS (5) 2/3 PR 2 died Openshaw 2000 [55] MS (11, 8 transplanted) 7/8 PR alive Kozak 2000 [56] Crohn's disease (2) 2/2 remission alive Burt 2003 [57] Mixed (7) 4/7 remission 1 died Rosen 2000 [58] Mixed ( maintainable vital organ function to ensure a decent quality of life if the immunological/inflammatory process were arrested or reversed. The patient should have sufficient capacity to withstand the HSCT procedure.…”