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Aim: This prospective study assessed the long-term ocular and visual outcomes of children with mucopolysaccharidoses type I Hurler syndrome (MPS IH) who were treated with haematopoietic stem cell transplants (HSCT)., Methods: Clinical ophthalmological assessments were performed on eight patients at the St Erik Eye Hospital, Huddinge, Stockholm, Sweden, from 2001-2018: The median age at diagnosis and HSCT were 12.2 (range 5.0-16.4) and 16.7 (8.0-20.4) months. The last eye examination was at a median of 13.4 (6.3-19.0) years and follow-up lasted a median of 12.0 (5.0-17.4) years., Results: Poor visual acuity, poor night vision and, or, photophobia were reported by six children. The best corrected visual acuity at the last visit was a median of 0.4 and 0.5 in the right and left eye and had declined significantly in two patients. Corneal opacities had increased despite HSCT in five patients. High hyperopia, at a median of +6 Dioptres, occurred in all patients and stiff corneas in all four patients that were measured. The patients' corrected intraocular pressures were normal. Retinal degeneration was identified in two patients., Conclusion: Despite HSCT, the long-term follow-up of patients with MPS IH showed reduced visual acuity due to corneal opacities or retinal degeneration., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: The aim of this study was to study long-term visual outcome and cataract development in children and adolescents after hematopoietic stem cell transplantation (HSCT) in childhood., Methods: Best corrected visual acuity (BCVA), refraction and lens status were examined in a prospective study of 139 children and adolescents., Results: In total, 139 patients (58 female), median age 6.6 years at HSCT (range 0.4-17.5 years), were followed up for a median of 8.0 years (1-19.4 years). Median BCVA in the better eye was 1.0 decimal. Altogether 19 of 131 patients developed cataract requiring surgery, while 46 developed less prominent lens opacities and 66 had clear lenses at time of latest follow-up. Patients conditioned with total body irradiation had a higher risk of developing lens opacities or cataract (p < 0.0001) as did patients with malignant disease, irrespective of irradiation treatment (p < 0.0001). Cumulative analysis showed that 50% of all patients had developed lens opacities/cataract after 10.2 years. Patients who ultimately needed cataract surgery developed cataract earlier than others (p = 0.006)., Conclusion: Lens opacities or cataract were more common in children or adolescents with malignant disease and after conditioning with irradiation. Regular ophthalmological follow-up is important after HSCT for early intervention to avoid amblyopia., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Chronic granulomatous disease (CGD) is a rare X-linked or autosomal recessive primary immune deficiency characterized by recurrent, life-threatening bacterial and fungal infections. Mortality rates are high with conventional treatment. However, haematopoietic stem cell transplantation (HSCT) offers cure. Here, we compare the outcome of HSCT in 14 Swedish patients with CGD to that in 27 patients with CGD who were given conventional treatment., Methods: Forty-one patients in Sweden were diagnosed with CGD between 1990 and 2012. From 1997 to 2012, 14 patients with CGD, aged 1-35 years, underwent HSCT and received grafts either from an HLA-matched sibling donor or a matched unrelated donor., Results: Thirteen of the 14 transplanted patients are alive and well. Mean age at transplantation was 10.4 years, and the mean survival time was 7.7 years. In contrast, seven of 13 Swedish men or boys with X-linked CGD who were treated conventionally died from complications of CGD at a mean age of 19 years, while the remaining patients suffered life-threatening infections., Conclusion: The outcome of the patients who underwent HSCT supports HSCT as being the preferable treatment for severe CGD. Our results advocate early HSCT for all patients with X-linked CGD, using grafts from either a matched sibling donor or a matched unrelated donor., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents., Methods: We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia., Results: The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years., Conclusion: The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.

Unlabelled: Familial haemophagocytic lymphohistiocytosis (FHL) is a rare, autosomal recessive disease of infancy and early childhood clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, rash, neurological symptoms and icterus. Common laboratory findings include cytopenia, elevated liver enzymes, hyperbiliriubinaemia, hypofibrinogenaemia and hypertriglyceridaemia. The natural killer cell function is frequently decreased or absent. A diffuse lymphohistiocytic infiltration is seen in the reticuloendothelial system, often with haemophagocytosis. Molecular diagnosis is available in a minority of FHL families. Without adequate treatment and bone-marrow transplantation, the disease is fatal. A 6-wk-old child with FHL is presented. Shortly before the clinical onset of the disease, blood testing and bone-marrow examination had been carried out. All results were considered normal at that time., Conclusion: Blood tests and bone-marrow examination may be normal shortly before the clinical presentation and therefore do not exclude the diagnosis of FHL. There is a need for extended molecular diagnostic possibilities.

Three children with adrenoleukodystrophy (ALD) underwent allogeneic bone marrow transplantation (BMT) between 1992 and 1993. The first boy had attention deficits, marked neuropsychological deficits and widespread demyelination in the frontal lobes on MRI before transplantation. Four years later he has mentally deteriorated and the demyelination on MRI has progressed. The second boy had no symptoms but had white matter lesions on MRI when diagnosed. He was regularly followed with MRI and neuropsychological investigations until BMT 18 months later. A progress of the lesions was noted on the initial MRI investigations, and 4 months before BMT a worsening of deficits in attention and kinaesthetic praxis could be observed. He rapidly deteriorated after the transplantation and died 18 months later. Both PCR and in situ hybridization confirmed the presence of donor cells in the brain. The third boy had no symptoms but white matter lesions on MRI when diagnosed. The neuropsychological tests remained normal but a slight progress was observed on MRI just before transplantation. This boy is still healthy 3.5 years after BMT. BMT as treatment for ALD has to be considered very early, even if a child without symptoms but signs of demyelination on MRI, if a suitable donor is available.

Twenty-eight out of 31 children that underwent bone marrow transplantation (BMT) from unrelated donors between 1984 and 1995 received HLA-A, HLA-B and HLA-DR matched unrelated donor (MUD) marrows as defined by serologic HLA class I and genomic HLA class II typing. Compared with 28 case-matched controls transplanted with HLA identical sibling donors, MUD patients received a more intensive conditioning. Twenty-six patients (93%) engrafted while two died of septicaemia during the aplastic phase. Two patients rejected their grafts and four developed Evans syndrome. All controls engrafted without incidents of rejection or Evans syndrome. The probability of acute graft-versus-host disease (GVHD) of grade II or above was 27% after MUD-BMT and 7% in the controls. The 5-year probability of survival was 60% in MUD patients and 89% after sibling BMT (p = 0.03). Leukaemia-free survival was 60% with one relapse in the MUD patients, and 59% with five relapses in the sibling group. Three children who received a mismatched donor marrow died, two of severe GVHD and one after graft rejection. In conclusion, today, a matched unrelated donor BMT is an acceptable alternative for many children who need a BMT but lack a suitable related donor.

The study included 6 children (aged 4-14 years) receiving a conditioning regimen for bone marrow transplantation (BMT) and 14 children (aged 2 14 years) with bone marrow transplants (13 allogeneic, 1 autologous). The children underwent flexible fibre-optic bronchoscopy (FFB) with bronchoalveolar lavage during 6 and 17 episodes of pneumonia, respectively. The aim was to compare the results of the two groups with respect to bronchoscopy findings, pneumonia-causing agents and outcome. During the conditioning regimen, the aetiological agents were recovered by bronchoscopy in 1/6 (17%) episodes and revealed by autopsy in another episode. In three episodes where the aetiology was uncertain, bacterial pneumonia was suspected in two, and Candida pneumonia in one. In episodes after transplantation the aetiological agents were recovered from bronchoscopy material in 14/17 (82%) patients. Autopsy confirmed the premortal diagnosis in the four children who died. In three episodes, bacterial pneumonia was clinically suspected. Based on clinical manifestations, FFB and autopsy findings, bacterial and fungal pneumonia were the most common diagnoses both during conditioning and after BMT. Fungal pneumonia was the most common cause of death in both groups.