ORIGINAL ARTICLE Prospective Evaluation of Clinical and Laboratory Effects of Intrathecal Chemotherapy on Children With Acute Leukemia Ilan Keidan, MD,* Bela Bielorei, MD,† Haim Berkenstadt, MD,* Arik Aizenkraft, MD,† Ran Harel, MD,‡ Ruth Huna-Baron, MD,§ and Chaim Kaplinsky, MD† Summary: The objective of this prospective 18-month study was to evaluate the clinical and laboratory effects of repeated intrathecal injections of chemotherapy in children with acute leukemia. All procedures were performed under general anesthesia, and compli- cations were prospectively recorded. Laboratory measurements in- cluded lumbar puncture opening pressure, cerebrospinal fluid (CSF) chemistry, and cell count and morphology. Central venous pressure and ophthalmologic examinations were also performed. Forty-seven children underwent 247 intrathecal injections of chemotherapy. Ad- verse effects (13.7% of the procedures) included nausea and vomiting, back pain, and headache. One child each had transient cauda equina syndrome, transient communicating hydrocephalus, and persistent sacral plexus injury. The mean lumbar puncture open- ing pressure was significantly higher after intrathecal therapy than before (22 6 8 vs. 15 6 9 cm H 2 O, P = 0.02) and higher than reported in age-matched children without leukemia. All CSF chemistries, cell count, and morphology were normal. The overall incidence of com- plications was 13.7%. Most were mild and resolved quickly, but significant neurologic complications did occur. Lumbar puncture opening pressure was significantly higher in children with acute leukemia after intrathecal chemotherapy. Key Words: lumbar puncture, intrathecal chemotherapy, acute leukemia, complications, neurotoxicity, post-dural puncture headache, increased intracranial pressure (J Pediatr Hematol Oncol 2005;27:307–310) T he recognition that central nervous system (CNS) re- currence constituted a major obstacle to overall treatment success in patients with leukemia stimulated efforts to prevent CNS involvement. The concept of CNS preventive therapy is based on the premise that the CNS acts as a sanctuary site in which leukemic cells reside, protected by the blood–brain barrier from systemically administered antileukemic drugs. Since the mid-1960s, intrathecal chemotherapy has constituted the standard prophylaxis and treatment of CNS leukemia. 1 Although lumbar puncture (LP) for chemotherapy administration is frequently performed in the pediatric hematology-oncology clinic, our knowledge of the clinical and laboratory effects, as well as the incidence of complications, is limited. Such information is crucial in view of complications, such as post-dural puncture headache (PDPH) and backache, that might influence the patient’s well-being, 2–4 as well as intrathecal chemotherapy-related neurotoxicity that may cause transient or permanent neurologic deficits. 5,6 We conducted this study to learn the clinical and laboratory effects associated with repeated intrathecal che- motherapy in children with acute leukemia and to establish the incidence of complications. METHODS After ethics committee approval and informed consent from parents, patients under the age of 16 who required intrathecal chemotherapy for CNS prophylaxis while being treated for acute leukemia at our institution during the 18- month study period were enrolled. Children with proven CNS involvement were excluded from the study. All the patients received intravenous granisetron (40 mcg/kg) for prevention of chemotherapy-induced nausea and vomiting. No local anesthetics were used in any of the patients. LP was performed under general anesthesia with a propofol bolus of 3 mg/kg followed by a continuous infusion at a rate of 100 mcg/kg/min. Ventilation was controlled using a face mask with 100% oxygen. Once anesthetized in the supine position, the patient was turned to a lateral decubitus position. The choice of needle size and type was left to the discretion of the pediatric hemato-oncologist who performed the procedure. LP was performed with the patient’s hips flexed, but the legs were straightened once CSF was detected and a manometer had been connected. 7 Once opening pressure was measured, 3 mL of CSF was collected. Intrathecal triple che- motherapy (methotrexate, cytosine arabinoside, and hydro- cortisone) was injected according to the institutional protocol (ALL-BFM 95). 8 Each drug was diluted in normal saline in a separate syringe according to the patient’s age. The total Received for publication August 3, 2004; accepted April 25, 2005. From the *Department of Anesthesia and Intensive Care, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; †Department of Pediatric Hemato-Oncology, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡Department of Neurosurgery, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and §Department of Ophthalmology, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Reprints: Ilan Keidan, MD, Departments of Anesthesia and Intensive Care, Sheba Medical Center, Tel Hashomer 52621, Israel (e-mail: keidan@ 012.net.il). Copyright Ó 2005 by Lippincott Williams & Wilkins J Pediatr Hematol Oncol  Volume 27, Number 6, June 2005 307