Prognostic factors in juvenile idiopathic arthritis.

Prognostic factors in juvenile arthritis are related to many variables that must be evaluated according to the different subtypes. The International League of Associations of Rheumatologists (ILAR) recently proposed six different categories referred to as the Durban criteria, under the eponym of juvenile idiopathic arthritis (JIA). The aim of this classification was to define homogeneous groups according to their clinical and biologic features. The prognostic factors were classified into the different categories of JIA. A poor outcome in the systemic form correlated with markers of disease activity, such as fever and polyarticular involvement, within the first 6 months. The risk of joint destruction in oligoarthritis correlated with the severity of arthritis within the first 2 years. Polyarthritis with positive rheumatoid factor is associated with marked disability in adulthood. In a group of psoriatic patients, the risk of developing sacroiliitis is higher in male and HLA-B27-positive patients. Patients with enthesitis-related arthritis with lower limb, knee, and tarsal involvement also are at greater risk of developing sacroiliitis. Chronic uveitis is a complication of JIA observed mainly in patients with oligoarthritis associated with positive antinuclear antibodies in serum. Secondary amyloidosis is observed mainly in children with systemic JIA. The long-term outcome must be discussed according to the various therapies. Corticosteroids contribute to growth retardation and osteoporosis, for which the use of human recombinant growth hormone and biphosphonates may be an option. Newer encouraging therapies such as anticytokines have been proposed for children with active disease. Autologous stem cell transplantation is being evaluated in some centers with promising results; however, it has a high rate of mortality. Further discussion regarding which patients should undergo autologous stem cell transplantation is needed, as is further discussion regarding the technical adaptations necessary.

[T-cell-depleted HLA non-identical bone marrow transplantation in the child: prevention of graft-versus-host reaction by administration of donor T lymphocytes alloreactive against the recipient]. / Greffe de moelle osseuse T déplétée HLA non géno-identique chez l'enfant: prévention de la réaction du greffon contre l'hôte par adjonction de lymphocytes T du donneur dépourvus d'alloréactivité vis-à-vis du receveur.

The success of HSCT from HLA partially disparate donors depends on the development of new strategies able to efficiently prevent GVHD and to protect patients from infections and relapse. Using an immunotoxin (IT) directed against the alpha-chain (p55) of the human IL-2r (RFT5-SMPT-dgA), we have previously shown that it is possible to kill mature T cells activated towards a specific HLA complex by a one-way MLR. We designed a clinical trial assessing the effect of infusing increasing doses of T lymphocytes in the setting of children recipients of non HLA genetically identical HSCT. Thirteen patients have been enrolled from September 1998 to April 2000 and fourteen HSCT have been realized in 13 patients (pts). Donors were MUD in 3 cases and familial HLA partially disparate in the remaining cases. Allodepleted donor T cells were injected between day +14 and day +30 provided that ATG was undetectable in the serum and blood PMN counts was > 500/microliter. The mean age of these patients was 17 months (range 1 to 42). Diagnosis included immune deficient and malignant hemopathies. Three patients received 1 x 10(5) allodepleted T cell/kg, 7 patients received 4 x 10(5)/kg and 4 patients received 6 x 10(5)/kg allodepleted T cells. Full inhibition of MLR was achieved in 12 out of 14 cases. In two cases, a residual T cell reactivity to the recipient was observed (4 to 5%) and patients developed grade II aGVHD. aGVHD occurred in 4 out of 11 grafted patients (all grade II). No chronic GVHD has developed, so far. Three patients died from severe VOD or PHT at day +34, day 51 and day +166, while one infected patient by VZV, CMV and EBV before HSCT died 6 months after transplantation from meningoencephalitis and another patient died from relapse at day +291. The patient for which there was no engraftment died at day +48 from staphylococcus infection. Overall survival is 54%, with a median follow up of 8 months; the mean time to reach a blood lymphocyte count > 500 was 41 days, to reach a CD3 count > 300 microliters 63 days (20-111), CD4 > 200 microliters 97 days and positive mitogen-induced proliferation 90 days. In three patients, a tetanus-toxoid positive proliferation was detected before immunization. From this intermediate analysis, we conclude that 1) specific allodepletion is an effective approach to prevent aGVHD in a haploincompatible setting, 2) data on immunological reconstitution suggest that infused T cells do survive and expand. A higher number of patients must be enrolled to determine the optimal number of T cells to infuse.

[Mortality in a pediatric hospital. Six-year retrospective study]. / Mortalité dans un hôpital pédiatrique. Etude rétrospective sur six ans.

AIMS: To define the characteristics of patients dying in a pediatric hospital, including causes and modes of death. PATIENTS AND METHODS: This retrospective, descriptive, epidemiologic study was performed between 1 January 1990 and 31 December 1995. All patients who died in the hospital between these dates were included. Patients already dead on arrival (sudden infant death syndrome, children deceased during their transport), and those whose hospital records could not be found, were excluded. RESULTS: A total of 375 children were studied, including 195 neonates. The sex ratio was 1.3. Ninety-one percent of deaths took place in three departments: intensive care, neurosurgery-neurology and oncology. Median duration of hospitalization was three days. The most common causes of deaths were accidents, neurologic diseases (particularly among neonates) and tumours. Analysis of modes of death revealed that 41.1% occurred following unsuccessful resuscitation, 38.8% were the result of withdrawal of life-support or a 'do not resuscitate' order and 21.6% resulted from brain death. Evolution of modes of death over the six years showed a reduction of cases with unsuccessful resuscitation, an increase in decisions of 'do not resuscitate' orders and withdrawal of life-support and no change in rates of brain death. Organs were made available for transplantation from 12 of the 81 children with brain death (14.8%). CONCLUSION: Accidents were the most common cause of death. The distribution of deaths showed a clear increase in withdrawal or withholding of life-support care, relying on ethical decisions, which are more frequent than some years ago.