Management of acquired aplastic anemia in children

The diagnosis of aplastic anemia in children requires exclusion of a variety of inherited or acquired BM failure syndromes with similar phenotypes. An efficient diagnostic plan is important because time from diagnosis to 'final' treatment is directly related to outcome regardless of the therapeutic option chosen. The gold standard of therapy remains hematopoietic SCT with a graft of BM cells for those children with matched sibling donors. Conversely for children without a sibling donor the high response and markedly improved overall survival rates of combined immunosuppressive therapy have proven robust, especially when horse derived anti-thymocyte globuline plus ciclosporine A are used. Incomplete response, relapse and progression to myelodysplasia/leukemia however have emerged as significant long-term issues. Improvements in outcome of alternative donor transplantation and the use of established and novel immunosuppressive agents provide multiple alternatives for treating refractory or relapsed patients. Regardless of the type of therapeutic approach, patients require centralized treatment in a center of excellence, ongoing monitoring for recurrence of disease and/or therapy-related immediate side effects and long-ternn effects. Bone Marrow Transplantation (2013) 48, 191-195; doi:10.1038/bmt.2012.235; published online 7 January 201

Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome

Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods: Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p. C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results: Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 mu kat/kg protein (patient 1) and from 3.6 to 17.9 mu kat/kg protein (patient 2) (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion: This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT

Aplastisk anemi hos barn botas med immunsuppression.

Acquired aplastic anemia (AA) is considered to be an autoimmune mediated disease whereas in inherited bone marrow failure syndromes the genetic abnormalities account for the bone marrow dysfunction. The only curative treatment for inherited AA is hematopoietic stem cell transplantation (HSCT). Successful treatment for acquired AA has traditionally been considered with HSCT, whereas single agent therapy with different immunosuppressive (IS) drugs has been disappointing as alternative treatment modality when sibling donors were lacking. Over the last decades however, treatment with combined IS (e.g. Cyclosporin-A, CsA, + Anti Thymocyte Globuline, ATG, has made great progress, resulting in hematological reconstitution comparable with results achieved with HSCT. We present a single centre retrospective analysis of 24 children with primary marrow failure at onset and treated subsequently during the years 1981-2002. 16 children were diagnosed with acquired severe aplastic anemia (SAA), 6 Fanconi anemia (FA), 1 Seckel syndrome and 1 with congenital amegakaryocytic thrombocytopenia. International randomized co-operative studies are required in order to gain knowledge on best treatment options of the disease. Long-term follow-up is of vital importance in order to elucidate the risk of secondary clonal diseases (PNH, MDS and leukemia) and other late effects

Fulminating clostridial septicemia in children treated for lymphoproliferative disorders

Overwhelming Clostridium septicum infection in 2 children, 1 and 4 yr old, with acute lymphoblastic leukemia and B-cell non-Hodgkin malignant lymphoma, respectively, as well as fatal C. perfringens infection in a 3-yr-old child with histiocytosis-X are reported. A neutropenic patient with fever, abdominal symptoms and hypotension--but otherwise being well--must be suspected of having clostridial disease. The most alarming feature is shock and rapid course

Arterial occlusion due to Listeria meningoencephalitis in an immunocompromised boy

Sequential CAT scan studies of the brain were performed in a 7-year-old boy with Listeria monocytogenes serotype 1 meningoencephalitis. The infection occurred while he was receiving maintenance chemotherapy for T-cell non-Hodgkin lymphoma. A lesion in the right hemisphere during the infection resulted in an excessive enlargement of the right ventricle 10 months later, most probably caused by arterial occlusion

Reversible changes on computed tomography scans of the brain during induction therapy for acute lymphoblastic leukemia in children

Children with acute lymphoblastic leukemia (ALL) have been shown to develop changes on computed tomography (CT) scans of the brain. These changes are seen both during and after therapy. Some of the results have been contradictory. Nine children with ALL were examined by CT of the brain during induction therapy. All children showed normal CT scans on the day of diagnosis. One month later all had dilatation of the ventricles and widened sulci. During the next 9 months the CT scans gradually were normalized. We conclude that such changes in CT scans of the brain are transitory and are caused by the high dose of prednisolone administered during induction therapy