Abstract
Methotrexate and cytarabine arabinoside are frequently administered intrathecally in the prophylaxis and treatment of patients with hematological malignancies. Myelopathy as a complication of intrathecal (IT) chemotherapy is rare in adults, with most of the cases described in the literature occurring in the pediatric population. Between January 2010 and March 2014, 587 newly diagnosed B cell acute lymphoblastic leukemia and 24 chronic myeloid leukemia lymphoid blast phase patients were seen at The University of Texas MD Anderson Cancer Center. This case series discusses seven adult cases deemed to have IT chemotherapy-induced myelopathy between 2010 and 2014 at MD Anderson Cancer Center. Five out of the seven patients had T2 abnormalities involving the dorsal columns of the spinal cord. An elevated myelin basic protein level was noted in the two patients in whom it was checked. The wide range of dosage and timing with respect to IT chemotherapy administration suggests an idiosyncratic reaction or individual threshold to the development of myelopathy. By describing the largest case series of myelopathy in adults, we aim to raise awareness about this rare albeit devastating complication. Based on the seven cases described we would recommend—MRI of the spine with T2-weighted imaging in the sagittal and axial planes in leukemia patients with unexplained myelopathy and consideration to delay IT chemotherapy until after an extensive work-up to rule out CNS leukemia. Though more data are needed on the use of folate metabolites, preliminary results have shown some promise in the treatment of methotrexate-induced myelopathy and may be a potential consideration for future patients suspected to have chemotherapy induced myelopathy.
Similar content being viewed by others
References
McLean DR, Clink HM, Ernst P, Coates R, al Kawi MZ, Bohlega S, Omer S (1994) Myelopathy after intrathecal chemotherapy. A case report with unique magnetic resonance imaging changes. Cancer 73:3037–3040
Skullerud K, Halvorsen K (1978) Encephalomyelopathy following intrathecal methotrexate treatment in a child with acute leukemia. Cancer 42:1211–1215
Bay A, Oner AF, Etlik O, Yilmaz C, Caksen H (2005) Myelopathy due to intrathecal chemotherapy: report of six cases. J Pediatr Hematol Oncol 27:270–272
Kantarjian HM, O’Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, Ha CS, Keating MJ, Murphy S, Freireich EJ (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18:547–561
Rytting ME, Thomas DA, O’Brien SM, Ravandi-Kashani F, Jabbour EJ, Franklin AR, Kadia TM, Pemmaraju N, Daver NG, Ferrajoli A, Garcia-Manero G, Konopleva MY, Cortes JE, Borthakur G, Garris R, Cardenas-Turanzas M, Schroeder K, Jorgensen JL, Kornblau SM, Kantarjian HM (2014) Augmented Berlin-Frankfurt-Munster therapy in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL). Cancer. doi:10.1002/cncr.28930
Cortes J, O’Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM (1995) The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood 86:2091–2097
Wolff L, Zighelboim J, Gale RP (1979) Paraplegia following intrathecal cytosine arabinoside. Cancer 43:83–85
Chabner BA, Longo DL (2011) Cancer chemotherapy and biotherapy: principles and practice. Lippincott Williams & Wilkins, Philadelphia
Watterson J, Toogood I, Nieder M, Morse M, Frierdich S, Lee Y, Moertel CL, Priest JR (1994) Excessive spinal cord toxicity from intensive central nervous system-directed therapies. Cancer 74:3034–3041
Dunton SF, Nitschke R, Spruce WE, Bodensteiner J, Krous HF (1986) Progressive ascending paralysis following administration of intrathecal and intravenous cytosine arabinoside. A Pediatric Oncology Group Study. Cancer 57:1083–1088
De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R (2014) Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE–5-a population-based study. Lancet Oncol 15:23–34. doi:10.1016/s1470-2045(13)70546-1
Pulte D, Gondos A, Brenner H (2009) Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980s to the early 21st century. Blood 113:1408–1411. doi:10.1182/blood-2008-06-164863
Pulte D, Redaniel MT, Jansen L, Brenner H, Jeffreys M (2013) Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups. Haematologica 98:222–229. doi:10.3324/haematol.2012.063602
Chamberlain MC (2012) Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol 109:143–148. doi:10.1007/s11060-012-0880-x
Teh HS, Fadilah SA, Leong CF (2007) Transverse myelopathy following intrathecal administration of chemotherapy. Singapore Med J 48:e46–e49
Glantz MJ, Cole BF, Glantz LK, Cobb J, Mills P, Lekos A, Walters BC, Recht LD (1998) Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 82:733–739
Pouw MH, Hosman AJF, van Middendorp JJ, Verbeek MM, Vos PE, van de Meent H (2009) Biomarkers in spinal cord injury. Spinal Cord 47:519–525
Ackermann R, Semmler A, Maurer GD, Hattingen E, Fornoff F, Steinbach JP, Linnebank M (2010) Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. J Neurooncol 97:425–427. doi:10.1007/s11060-009-0028-9
Drachtman RA, Cole PD, Golden CB, James SJ, Melnyk S, Aisner J, Kamen BA (2002) Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity. Pediatr Hematol Oncol 19:319–327. doi:10.1080/08880010290057336
Acknowledgments
Mrs. Sherry A Pierce for her help with data collection.
Conflict of interest
Authors report no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
David Cachia and Carlos Kamiya-Matsuoka contributed equally to the preparation of this manuscript.
Naval Daver and Karin Woodman are co-corresponding authors.
Rights and permissions
About this article
Cite this article
Cachia, D., Kamiya-Matsuoka, C., Pinnix, C.C. et al. Myelopathy following intrathecal chemotherapy in adults: a single institution experience. J Neurooncol 122, 391–398 (2015). https://doi.org/10.1007/s11060-015-1727-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-015-1727-z