[Apheresis tolerance and acceptability in the child weighing 30 kg or less, with the exception of infants]. / Tolérance et acceptabilité des aphérèses chez l'enfant de 30 kg ou moins á l'exception du nourrisson.

Over the ten past years, we performed 336 apheresis among 51 children who were 19 months to 15 years old (10 to 30 kg body weight). 3 types of apheresis were carried out. 14 red blood cell exchange, 293 plasma exchanges and 29 peripheral blood stem cell collections (CSP). 5 different types of continuous or discontinuous flow machines have been used. Technical adaptations depending on patient blood volume, hematocrit, type of machine used and apheresis performed permitted us to obtain a very good tolerance and acceptability. According us, the apheresis should be used each time this treatment is needed in the child, because of the very low frequency of side effects.

[Intensive immunosuppression in progressive multiple sclerosis. An open study comparing 3 groups: cyclophosphamide, cyclophosphamide-plasmapheresis and control subjects. Results after 3 years]. / Immunosuppression intensive dans la sclérose en plaques progressive. Etude ouverte comparant trois groupes: cyclophosphamide, cyclophosphamide-plasmaphérèses et témoins. Résultats à trois ans.

Three groups of 10 patients each with multiple sclerosis (MS) in a progressive phase were openly matched on the basis of age and invalidity (DSS Kurtzke). Variance analysis showed no significant difference between them for the main MS features. Group 1 received cyclophosphamide for 3 weeks (mean total dose: 152 mg/kg) with methylprednisolone (mean total dose: 2.77 g). Group 2 had a mean number of 9 plasma exchanges prior to a cyclophosphamide-methylprednisolone regimen similar to Group 1 (mean total dose of cyclophosphamide: 160 mg/kg and of methylprednisolone: 3.16 g). Group 3 was made up of controls. At three years, the proportion of stabilized and improved cases was 6/10 in group 1, 9/10 in Group 2 (statistically significant when compared with Group 1), and 0/10 in Group 3. The study of the variations of invalidity (DSS gains) showed a clear significant benefit in the treated groups when compared to controls, but no difference between the treated groups. Longitudinal studies showed that the mean therapeutic benefit was about 2.5 years. The role of cyclophosphamide and of plasma exchanges in these results is discussed.

Restoration of high immunoglobulin gene expression in chronic lymphoid leukemia: a possible application for gene therapy.

In this study, using interleukin-2 and gamma interferon, we first induced the differentiation into plasma cells of primary chronic lymphoid leukemic B cells from patients whose T cells failed to produce interleukin-2. We next demonstrated that these malignant primary B lymphocytes (i.e., lymphocytes which have not been subjected to any procedure aiming at their immortalization or their transformation into cell lines) functionally expressed transfected genes under the control of exogeneous Ig promoters and enhancers during their terminal differentiation into plasma cells. We discussed the possibility of applying this approach to gene therapy to correct this type of lymphocytic leukemia in man.

Successful treatment of acquired factor VIII antibody by extracorporeal immunoadsorption.

We report the successful treatment of a 59-year-old woman with acquired factor VIII inhibitor. The patient who had an extensive leg hematoma with a resultant neurologic defect was treated with extracorporeal immunoadsorption (IA) using protein A-Sepharose, factor VIII concentrates, azathioprine, and methyl-prednisolone. Extracorporeal IA reduced the titers of the inhibitor so that factor VIII concentrates could raise the level of factor VIII coagulant activity and stop the bleeding.

Transplant of rhesus-positive bone marrow in a rhesus-negative woman having anti-rhesus D alloantibodies.

A woman affected by acute myeloblastic leukemia was grafted with HLA A, B and D compatible rhesus-positive bone marrow from her brother. Before grafting, she had anti-D alloantibodies (1/512 IAT, 2.9 micrograms/ml). To prevent the destruction of donor red blood cells, four plasma exchanges and a conditioning regimen (total-body irradiation 800 rad, cyclophosphamide, methotrexate) were carried out to decrease anti-D from 2.9 to less than 0.02 micrograms/ml on day 0. The anti-D level was 0.8 micrograms/ml on day 12 and was decreased to 0.2 micrograms/ml by eight plasma exchanges until day 35. Anti-D antibodies were undetectable with Lalezari's technique on day 45. Engraftment was obtained on day 25 (3,000 leukocytes/mm3 and 50% erythroblasts in bone marrow). The patient died from aspergillosis and graft-versus-host disease on day 54. This observation shows that an engraftment of rhesus-positive bone marrow in a recipient with anti-D antibody is possible.

Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies.

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma (n = 148), Hodgkin's disease (n = 22) and multiple myeloma (n = 30). The variables predicting the collection of a minimal (>2.5 x 10(6)/kg) or a high (>10 x 10(6)/kg) CD34+ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy (n = 49) or high-dose cyclophosphamide, given alone (n = 55) or combined with high-dose VP16 (n = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34+ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count (P=0.06 and 0.0008 respectively). The target to collect a high CD34+ cell count was negatively associated with the number of previous chemotherapy regimens (P=0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield (P=0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.

High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation.

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x 10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+) cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P < .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34(+) cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 x 10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.