{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:53:27Z","timestamp":1772189607699,"version":"3.50.1"},"reference-count":17,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>Central nervous system (CNS) involvement is a severe complication of BCR-ABL-positive leukemia after allogenic stem cell transplantation (alloSCT) associated with fatal outcome. Although second-generation tyrosine-kinase inhibitors (TKI) such as nilotinib have shown activity in systemic BCR-ABL<jats:sup>+<\/jats:sup>disease, little data exists on their penetration and efficacy within the CNS. Four patients (3 male, 1 female; age 15\u201349) with meningeal relapse after alloSCT and subsequent treatment with nilotinib were identified. A total of 17 cerebrospinal fluid (csf) and serum samples were assessed for nilotinib concentration and patient outcome was recorded. Nilotinib concentrations showed a low median csf\/plasma ratio of 0.53% (range 0.23\u20131.5%), yet pronounced clinical efficacy was observed with long-lasting responses (&gt;1 year) in three patients. Comparison with historical data showed a trend towards superior efficacy of nilotinib versus imatinib. Despite poor csf penetration, nilotinib showed significant clinical activity in CNS relapse of BCR-ABL<jats:sup>+<\/jats:sup>leukemias. As nilotinib has a high protein-binding affinity, the low-protein concentration in csf could translate into a relatively higher amount of free and therefore active nilotinib in csf as compared to blood, possibly explaining the observed efficacy. Thus, treatment with a 2nd generation TKI warrants further investigation and should be considered in cases of CNS relapse of BCR-ABL-positive leukemia after alloSCT.<\/jats:p>","DOI":"10.1155\/2014\/637059","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T21:37:54Z","timestamp":1402954674000},"page":"1-7","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy and Pharmacologic Data of Second-Generation Tyrosine Kinase Inhibitor Nilotinib in BCR-ABL-Positive Leukemia Patients with Central Nervous System Relapse after Allogeneic Stem Cell Transplantation"],"prefix":"10.1155","volume":"2014","author":[{"given":"Mark","family":"Reinwald","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Schleyer","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"},{"name":"Department of Internal Medicine, Klinikum Merseburg, Wei\u00dfe Mauer 52, 06217 Merseburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Kiewe","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charit\u00e9 Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Wolfgang","family":"Blau","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charit\u00e9 Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Burmeister","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charit\u00e9 Berlin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Pursche","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charit\u00e9 Berlin, Hindenburgdamm 30, 12203 Berlin, 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