[The possible role of microchimerism in the aetiology of autoimmune diseases]. / Mogelijke rol van microchimerisme bij het ontstaan van auto-immuunziekten.

The aetiology of several autoimmune diseases has not yet been elucidated. Microchimerism, the persistence of small numbers ofallogeneic cells in an individual, has been mentioned recently in connection with the occurrence of autoimmune diseases such as systemic sclerosis and juvenile inflammatory idiopathic myopathy. These allogeneic cells can originate from mutual foeto-maternal exchange of blood cells during pregnancy or from a donor after blood transfusion or (organ) transplantation. In some cases, a syndrome then develops that resembles the chronic graft-versus-host reaction after stem-cell transplantation, in which allogeneic cells react with autologous cells. Studies on microchimerism in patients with systemic sclerosis and juvenile inflammatory idiopathic myopathy, compared to controls, sometimes reveal a clearly increased prevalence of microchimerism in patients. However, microchimerism can also be found in healthy individuals. Direct proof of a causal relation between microchimerism and autoimmune diseases does not exist. Additional genetic or environmental factors may be partly responsible for a disturbed balance between tolerance and aggression.

Quality of life in adults following bone marrow transplantation during childhood.

SUMMARY: Quality of life (QOL) was assessed in 22 young adults, 14 years - on average- after having received bone marrow transplantation (BMT) during childhood at the Leiden University Medical Center. All were disease-free and >16 years when interviewed. The sickness impact profile and the Medical Outcome Study 36-item Short Form Health Survey were used as generic questionnaires in the assessment of QOL. The Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) was used as a disease-specific measure of QOL. Coping was assessed by means of the Utrecht coping list. BMT-related variables were obtained from medical files. Of the generic QOL measures, most results fell within the normal range of functioning, although some illness-related impairment was reported on subscales for general and work-related functioning. Compared to a reference sample of patients who had received BMT as adults, patients involved in this study scored significantly higher on the 'emotional well-being' subscale of the FACT-BMT, indicating significantly better emotional functioning. The age at BMT and total body irradiation (TBI) were not related to patients' QOL. We can conclude that at long term, having received BMT during childhood does not negatively affect the QOL of patients. Bone Marrow Transplantation (2004) 33, 329-336. doi:10.1038/sj.bmt.1704345 Published online 1 December 2003

Paediatric allogeneic bone marrow transplantation for homozygous beta-thalassaemia, the Dutch experience.

We reviewed the results of the Dutch paediatric bone marrow transplant (BMT) program for children receiving HLA-identical BMT for beta-thalassaemia major over an 18-year period. In all, 19 patients underwent a total of 21 transplants in our treatment centre between July 1984 and February 2002. Eight females (age 0.3-12 years; median 5 years) and 11 males (age 0.8-18 years; median 6 years) were included. Information, prospectively collected, included molecular defects, donor genotype, beta/alpha-globin expression rates, serum ferritin levels, hepato-splenomegaly, chelation history, virology screening, liver pathology together with post-transplant outcome inclusive of leucocyte chimerism. In total, 11 patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring in six patients. Of these, two children underwent a second successful SCT. For this group, overall event-free survival (EFS) and disease-free survival (DFS) were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was 55%. Subsequent addition of melphalan to the conditioning regimen resulted in long-term stable engraftment in all patients with an EFS/DFS for this group of 90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at 5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21 transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT beta/alpha synthetic ratio measurement monitored donor erythroid engraftment and predicted rejection with a return to transfusion dependency. Maintained full donor chimerism is indicative of stable engraftment both for leucocyte and erythroid lineages, whereas mixed donor chimerism is not. Our results emphasise the importance of the conditioning regimen and post-transplant chimerism surveillance predictive of rejection or long-term stable engraftment.

Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits.

This is a retrospective analysis of 188 children who underwent total body irradiation (TBI) in one or two fractions before bone marrow transplantation (BMT) for a hematological disorder. While 139 children had eye shielding during TBI to decrease cataract formation, 49 did not. The blocks used for shielding caused cylindrical areas of decreased dose intensity in the brain. The aim of the study was to determine if there was an increased risk of relapse in the eyes or in the CNS after shielding of the eyes. The probability and severity of cataract formation with and without shielding were also evaluated. None of the 49 children without shielding had a relapse in their eyes or in the CNS after BMT. Of the children with shielding, none had a relapse in the eyes but two of the 139 (1.4%) had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21 evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts were present in eight of 21 (38%) patients without and two of 64 (3%) patients with shielding. The probability of staying cataract free for at least five years was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24 respectively. The relative risk of developing a cataract without shielding vs shielding was three (95% CI=1.5; 5.9). It appears that the incidence of relapse in the eyes and CNS is not increased when the eyes are shielded during TBI. Shielding increased the latency time of cataract formation and decreased the severity of cataracts.

Tube feeding and bone marrow transplantation.

BACKGROUND: Children undergoing bone marrow transplantation (BMT) have poor oral intake during the transplant period, caused mainly by the intensive therapy used for their conditioning. Nutritional support (NS) is almost always needed. Whenever possible, tube feeding (TF) is preferred to parenteral nutrition (PN) because its more physiologic and causes fewer complications. However, children undergoing BMT are usually parenterally fed. We, therefore, studied whether TF was tolerated in children undergoing BMT and whether the nutritional intake was adequate in comparison to PN. PROCEDURE: Two groups were compared: TF (n = 12) and PN (n = 22). If intolerance for TF occurred, additional or total PN was given. Nutritional status, intake, complications, and costs were assessed. RESULTS: Both groups had an adequate nutritional status and reached 85% of their nutritional requirements. TF was possible in 62% of the NS days and three children could be exclusively fed with TF. A longer pre-transplant duration of TF seemed to increase the enteral tolerance. Gastrointestinal symptoms were equally frequent in TF as in PN, but cholestasis was less frequent in TF. The mean nutritional cost per child in the TF group was 440 US dollars less than in the PN group. CONCLUSIONS: TF is possible and equal in efficacy to PN in children undergoing BMT, and may have budgetary benefits.

[Favorable current prognosis after HLA-identical bone marrow transplantation for children with required severe aplastic anemia; evaluation of 30 years of bone marrow transplantation at the Leiden University Medical Center]. / Tegenwoordig gunstige prognose na HLA-identieke beenmergtransplantatie bij kinderen met verworven ernstige aplastische anemie; evaluatie van 30 jaar beenmergtransplantaties in het Leids Universitair Medisch Centrum.

OBJECTIVE: To evaluate the results of 30 years of allogeneic HLA-identical bone marrow transplantation (BMT) as the treatment for children with acquired severe aplastic anaemia. DESIGN: Retrospective, descriptive. METHOD: Of all patients who underwent an HLA-identical sibling-donor BMT for severe aplastic anaemia at the Department of Paediatrics, Leiden University Medical Center, in the period 1971-2000, and had a follow-up period of at least 1 year, the medical data were reviewed. The patients were split into 2 groups: patients transplanted before 1989 (n = 24), and patients who had their BMT from 1989 onwards (n = 20). This was due to a change in the treatment policy, namely a reduction in the period between diagnosis and BMT, resulting in fewer blood transfusions as well as changes in the prophylaxis against graft-versus-host disease (GvHD) from 1989 onwards (combination therapy using methotrexate and cyclosporin). RESULTS: There was an increase in the 1-year actuarial survival rate from 67% in the period before 1989 to 90% thereafter. The incidence of GvHD has significantly decreased since the introduction, in 1989, of the combination therapy using methotrexate and cyclosporin, with only 1/20 patients suffering from acute GvHD versus 13/24 prior to 1989 (p = 0.002). No patients acquired chronic GvHD after 1989, whereas before 1989, 10 patients had acquired this (p = 0.001). CONCLUSION: The prognosis of allogeneic HLA-identical sibling transplantation for paediatric patients with severe aplastic anaemia has considerably improved over the last 30 years due to improved supportive care, a significant decrease in GvHD and a shorter period between diagnosis and BMT, with the result that less blood transfusions have been required and less sensitisation has occurred. The long-term survival chance has increased to 90%.