Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome‐positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid

• Published in: British journal of haematology Vol. 119; no. 1; pp. 106 - 108
• Main Authors: Takayama, Nobuyuki, Sato, Norihide, O'Brien, Stephen G., Ikeda, Yasuo, Okamoto, Shin‐ichiro
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.2002; Blackwell
• Subjects: acute lymphoblastic leukaemia; Adult; Antineoplastic agents; Antineoplastic Agents - blood; Antineoplastic Agents - cerebrospinal fluid; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Blood-Brain Barrier; central nervous system; Central Nervous System Neoplasms - blood; Central Nervous System Neoplasms - cerebrospinal fluid; Central Nervous System Neoplasms - drug therapy; Chemotherapy; Enzyme Inhibitors - blood; Enzyme Inhibitors - cerebrospinal fluid; Enzyme Inhibitors - therapeutic use; Female; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Philadelphia chromosome; Piperazines - blood; Piperazines - cerebrospinal fluid; Piperazines - therapeutic use; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - cerebrospinal fluid; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Pyrimidines - blood; Pyrimidines - cerebrospinal fluid; Pyrimidines - therapeutic use; Chromosomal aberration; Human; Enzyme; Transferases; Acute; Central nervous system; Imatinib mesylate; Enzyme inhibitor; Malignant hemopathy; Cerebrospinal fluid; Blood brain barrier; Philadelphia chromosome; Chemotherapy; Treatment; Protein kinase; Lymphoproliferative syndrome; Abnormal chromosome; Acute lymphocytic leukemia; Pharmacokinetics; Fusion protein; Hybrid gene
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03881.x

A 32‐year‐old woman with relapsed Philadelphia chromosome‐positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92‐fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood–brain barrier and has limited activity against CNS leukaemia.