ABSTRACT
Since 1988, 24 children have undergone haematopoietic stem cell transplantation (HSCT) for severe sickle cell disease (SCD) in our unit, 13 being grafted after having been exposed to hydroxyurea (HU) to control SCD-related complications. Different pre-transplant conditioning regimens were given over time: Bu14/Cy200 in six patients (group 1), Bu16/Cy200/antithymocyte globulin (ATG) in five (group 2) and Bu16/Cy200/ATG with HU prior to HSCT in 13 (group 3). The aim of this study is to compare the outcome after HSCT of these groups of patients, which differ according to pre-transplant drug exposure. Overall, 20 of the 24 transplanted children had stable engraftment and have remained free of SCD-related symptoms after HSCT; 19 of them are currently alive and cured of SCD. In group 1 (HU-, ATG-), we observed one unexplainable late death, one absent engraftment, one late rejection and one mixed stable chimerism. In group 2 (HU-, ATG+), we observed the absence of engraftment in two patients and one early rejection. In group 3 (HU+, ATG+), we observed no cases of either absent engraftment, mixed stable chimerism or late rejection. In our experience, pre-transplant treatment with HU seems to be associated with a lower incidence of rejection/absent engraftment in severe SCD patients. These results need to be confirmed with a larger number of patients.
Subject(s)
Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/therapy , Antisickling Agents/therapeutic use , Hematopoietic Stem Cell Transplantation , Hydroxyurea/therapeutic use , Child , Child, Preschool , Female , Graft Survival , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Seizures/etiology , Transplantation ConditioningABSTRACT
BACKGROUND: Pathogenesis of osteopetrosis is still debated. Testing the ability of osteoclastic progenitors to support the proliferation of functional cells may be useful in understanding pathogenesis. CASE REPORT AND METHODS: A diagnosis of osteopetrosis was made in a girl 1 month-old, born to consanguuineous parents. Bone marrow transplantation was uneffective at the age of 3 months but a second engraftment was successful at 5 months. Unfortunately, the patient died from severe thrombocytopenia at the age of 8 months. Long-term cultures of mononucleated cells from the patient's blood were performed before and after the bone marrow transplantation, with or without growth factors such as vitamin D3, IL-6 and IL-1. Similar studies were made from the patient's marrow obtained after transplantation; all results were compared with those obtained after culturing control cells from cord blood umbilical. RESULTS: Production of osteoclastic cells was mild in peripheral blood cultures; it was important in bone marrow cultures in presence of growth factors. CONCLUSION: These results suggest that osteopetrosis in our patient resulted from an intrinsic defect in progenitors of osteoclasts.
Subject(s)
Bone Marrow Transplantation , Osteoclasts/pathology , Osteopetrosis/pathology , Osteopetrosis/therapy , Blood Cells/pathology , Bone Marrow/pathology , Cell Differentiation , Cells, Cultured , Female , Humans , In Vitro Techniques , Infant , Postoperative PeriodABSTRACT
The model describing the binding of three ligands to the sites of a receptor is theoretically studied in order to characterize the binding interaction between two unlabelled ligands. For this, the binding of a third labelled ligand, the affinity of which is dependent on the presence of the unlabelled ligands, must be measured in different conditions. This paper describes an experimental strategy leading to an accurate determination of the equilibrium parameters of the model. This strategy, which assumes that the model is compatible with the data, rests on the determination of the optimal experimental conditions, i.e. the choice of the ligand concentrations which minimize the error of the parameter estimates. For this purpose, a computer program which runs on a microcomputer under the MS-DOS operating system has been elaborated on the basis of the D-optimization criterion. This work shows that such a computer analysis is essential to the determination of the optimal experimental design, even when very simple biochemical systems are considered.