caa a22 4500 477056237 CHVBK 20180405111347.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s002280050187 doi (NATIONALLICENCE)springer-10.1007/s002280050187 Tolerance Evaluation of L-asparaginase loaded in red blood cells [Elektronische Daten] [R. Kravtzoff, P. Colombat, I. Desbois, C. Linassier, J. P. Muh, T. Philip, J. Y. Blay, M. Gardenbas, P. Poumier-Gaschard, J. P. Lamagnere, M. Chassaigne, C. Ropars] Objective: A pilot clinical study was conducted to evaluate the toxicity of a single dose of L-asparaginase loaded in red blood cells (RBCs). Methods: Thirteen patients received a single dose of L-asparaginase in the range 30-200 IU ⋅ kg−1. The enzyme was loaded in one autologous blood unit using a lysis-resealing process. A control population of 33 patients receiving L-asparaginase intravenously were tested in parallel. IgG, IgM and IgE class anti-L-asparaginase antibodies were detected using specific radioimmunoassays. Results: L-Asparaginase pharmacodynamic parameters may be greatly improved by administration of the drug after internalisation in RBCs as compared to intravenous injection of free drug. The drug elimination was prolonged and similar to that of circulating carrier. After one injection of 30 IU ⋅ kg−1, plasma L-asparagine was eliminated in 10 days and this was extended to 50 days for 150-200 IU ⋅ kg−1. The drug was well tolerated and only transient variations were observed for some of the biological parameters measured. We did not reach the maximum tolerable dose (MTD) of L-asparaginase loaded in RBCs. No significant clinical toxicity was detected. In particular, no immune adverse effects were observed. Conclusion: This study opens new perspectives for the clinical utilisation of L-asparaginase. This mode of administration of the drug is able to improve pharmacodynamic parameters and enzymic efficacy and to increase the general tolerance of the treatment. Springer-Verlag Berlin Heidelberg, 1996 Key wordsL-Asparaginase nationallicence Acute lymphoblastic leukaemia nationallicence non-Hodgkin's lymphoma nationallicence red blood cells nationallicence tolerance study nationallicence Kravtzoff R. Laboratoire de Biopharmacologie Transfusionnelle, INSERM U. 316, CRTS, BP 2009, F-37020 Tours, France, FR aut Colombat P. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut Desbois I. Centre Regional de Transfusion Sanguine, Tours, France, FR aut Linassier C. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut Muh J. P. Service de Biochimie, CHRU, Tours, France, FR aut Philip T. Centre Léon Bérard, Lyon, France, FR aut Blay J. Y. Centre Léon Bérard, Lyon, France, FR aut Gardenbas M. Service d'Hématologie, CHRU, Angers, France, FR aut Poumier-Gaschard P. Centre Regional de Transfusion Sanguine, Tours, France, FR aut Lamagnere J. P. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut Chassaigne M. Centre Regional de Transfusion Sanguine, Tours, France, FR aut Ropars C. Laboratoire de Biopharmacologie Transfusionnelle, INSERM U. 316, CRTS, BP 2009, F-37020 Tours, France, FR aut https://doi.org/10.1007/s002280050187 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050187 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kravtzoff R. Laboratoire de Biopharmacologie Transfusionnelle, INSERM U. 316, CRTS, BP 2009, F-37020 Tours, France, FR aut NATIONALLICENCE 700 1- Colombat P. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut NATIONALLICENCE 700 1- Desbois I. Centre Regional de Transfusion Sanguine, Tours, France, FR aut NATIONALLICENCE 700 1- Linassier C. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut NATIONALLICENCE 700 1- Muh J. P. Service de Biochimie, CHRU, Tours, France, FR aut NATIONALLICENCE 700 1- Philip T. Centre Léon Bérard, Lyon, France, FR aut NATIONALLICENCE 700 1- Blay J. Y. Centre Léon Bérard, Lyon, France, FR aut NATIONALLICENCE 700 1- Gardenbas M. Service d'Hématologie, CHRU, Angers, France, FR aut NATIONALLICENCE 700 1- Poumier-Gaschard P. Centre Regional de Transfusion Sanguine, Tours, France, FR aut NATIONALLICENCE 700 1- Lamagnere J. P. Service Oncologie Médicale et Maladies du Sang, CHRU, Tours, France, FR aut NATIONALLICENCE 700 1- Chassaigne M. Centre Regional de Transfusion Sanguine, Tours, France, FR aut NATIONALLICENCE 700 1- Ropars C. Laboratoire de Biopharmacologie Transfusionnelle, INSERM U. 316, CRTS, BP 2009, F-37020 Tours, France, FR aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer