Accidental Overdose of Intrathecal Cytarabine in Children (May).

< Department of Pediatrics, University of Texas at Southwestern Medical Center, Dallas.
Annals of Pharmacotherapy (Impact Factor: 2.06). 04/2013; 47(5). DOI: 10.1345/aph.1S028
Source: PubMed


To report 2 cases of intrathecal cytarabine overdose in children with cancer, neither of whom underwent cerebrospinal fluid (CSF) exchange per current recommendations or developed apparent toxicity related to the event.

Case summary:
A 17-year-old female with newly diagnosed acute myeloid leukemia received 177 mg of intrathecal cytarabine rather than the appropriate dose of 70 mg. She was monitored closely with no apparent toxicity from the event. A 4-year-old boy with newly diagnosed precursor B-cell acute lymphoblastic leukemia received 175 mg of intrathecal cytarabine rather than the appropriate dose of 70 mg. CSF was immediately withdrawn and intrathecal hydrocortisone was instilled for possible antiinflammatory effect. He developed no apparent toxicity from the event.

Cytarabine is an important chemotherapeutic agent in the treatment of leukemia. One case report of intrathecal cytarabine overdose was identified in the literature, which recommended CSF exchange as management. Neither child in our report underwent CSF exchange or developed apparent toxicity related to the event. Institutional changes were made in both cases to prevent similar events.

These cases demonstrate that measures such as CSF exchange are not uniformly required for cytarabine overdose.

24 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Twenty-one children with acute nonlymphoblastic leukemia (ANLL) were treated with a combination regimen consisting of arabinosyl cytosine (Ara-C), 6-thioguanine (TG), and Adriamycin, The incidence of complete remission was 74%. For consolidation, addition courses of Ara-C and TG were given, followed by L-asparaginase. The maintenance program was the same as that for the lymphoblastic type (L-2) including intrathecal methotrexate for prophylaxis of meningeal leukemia. Of the 16 who were evaluable for the duration of complete remission, six developed bone marrow relapse, one meningeal leukemia within 3-14 months after entering complete remission and one was lost to follow-up. Eight remain in complete remission for 9-72 months. In five of eight, chemotherapy has been terminated after 3 years, and all continue in remission for 11-32 months post-treatment. Although the results do not compare well to those of the lymphoblastic morphology, long-term disease-free survival can be achieved with multiple-drug intensive treatment in childhood ANLL.
    Cancer 10/1977; 40(4):1417-21. DOI:10.1002/1097-0142(197710)40:4<1417::AID-CNCR2820400409>3.0.CO;2-Z · 4.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We analysed the results of three protocols from 1990 to 2005. Protocol I (1990-1996) consisted of a 2 year VAPA regime. Protocol II (1996-2003) on 1 year daunorubicin/cytarabine alternating with etoposide/cytarabine. Protocol III (2003-2005) on six cycles MRC AML 10 modified. Patients with de novo acute myeloid leukemia 0 to 18 years were included. Demographic and clinical characteristics were analysed. Patients with >100,000 leukocytes, M4 or M5 and primary CNS disease were considered high risk. We compared remission rate, overall and event-free survival. Descriptive statistics, chi square, Kaplan-Meier and long rank tests were used. One hundred forty-five patients were included, 46 in Protocol I; 60 in II and 39 in III. There were no differences in characteristics between groups, except for more low risk patients in Protocol II (61%vs. 43% and 41%. (p = 0.05). Remission rate for Protocol I was 52%, for II 50% and for III 92% (p = 0.0001). Relapse was 18, 30 and 35, respectively (p = 0.141). Five-year event-free survival was 17.9% +/- 6.6%, 15.5% +/- 4.1% and 43.5% +/- 4.1% (s.e) (p = 0.0002). Five-year overall survival was 19.5% +/- 8%, 17.2% +/- 5.9% and 51.2% +/- 4.1% (s.e) (p = 0.0002). The results were superior in the MRC-10 derived protocol.
    Leukemia & lymphoma 07/2009; 50(7):1132-7. DOI:10.1080/10428190902964768 · 2.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prompt and appropriate management measures are critical in order to achieve a favorable outcome after a major overdose of intrathecally (IT) administered methotrexate (MTX). Published information available to guide clinicians in the immediate management of this medical emergency is scant. Herein we describe a 6-year-old boy with acute lymphoblastic leukemia who received an inadvertent overdose of 600 mg of IT administered MTX instead of the intended dose of 12 mg. Severe acute neurotoxicity developed rapidly. Lumbar puncture and drainage of 15 mL of cerebrospinal fluid 2 hours after administration resulted in removal of 32% of the administered drug. Ventriculolumbar perfusion with 240 mL of warmed isotonic saline through ventricular and lumbar catheters for 3 hours resulted in removal of a total of 90% of the drug within 8 1/2 hours after administration. IT administration of 2,000 U of carboxypeptidase G2 (CPDG2), an enzyme that inactivates MTX, resulted in a further 150-fold reduction in cerebrospinal fluid MTX concentration. The patient experienced complete recovery. To our knowledge, this is the first reported case of the use of IT instillation of CPDG2 for the treatment of an overdose of IT administered MTX in a human, and it is only the second reported favorable outcome after an IT overdose of more than 500 mg of MTX. Minor IT overdoses of MTX can be managed by immediate lumbar drainage alone. Major overdoses may also necessitate prompt ventriculolumbar perfusion, IT instillation of CPDG2, and further supportive measures for a successful outcome after this infrequent but potentially catastrophic event.
    Mayo Clinic Proceedings 03/1996; 71(2):161-5. DOI:10.1016/S0025-6196(11)64508-4 · 6.26 Impact Factor
Show more


24 Reads
Available from