Subdural hematomas in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia receiving imatinib mesylate in conjunction with systemic and intrathecal chemotherapy

Imatinib mesylate and other tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL have had a favorable impact on the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). TKIs are generally well tolerated, but they can induce platelet dysfunction, which is of particular concern in the setting of thrombocytopenia in patients with acute leukemia. We present three patients with Ph+ALL receiving imatinib mesylate in conjunction with systemic and intrathecal chemotherapy who developed subdural hematomas (SDHs). All three were thrombocytopenic and had undergone repeated lumbar punctures for prophylactic intrathecal chemotherapy, but they were not coagulopathic and did not have meningeal leukemia. SDHs occurred in three of a total of 10 adult patients with Ph+ALL receiving imatinib mesylate in conjunction with systemic and intrathecal chemotherapy at our institution from 2007 to 2010, but in none of 22 adult patients with Ph-ALL receiving the same therapy without imatinib mesylate (p < 0.05). Patients with Ph+ALL receiving imatinib mesylate, and likely also dasatinib, in conjunction with systemic and intrathecal chemotherapy may be at increased risk of SDH, and should be closely monitored for subtle manifestations of this complication.