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Complications of Intrathecal Chemotherapy in Adults

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Complications of Intrathecal Chemotherapy in Adults View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Scholarly Commons@Baptist Health South Florida Baptist Health South Florida Scholarly Commons @ Baptist Health South Florida All Publications 2019 Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients Fernando Vargas Madueno Baptist Health Medical Group; Miami Cancer Institute, [email protected] Follow this and additional works at: https://scholarlycommons.baptisthealth.net/se-all-publications Citation Journal of Oncology (2019) 2019:4047617 This Article -- Open Access is brought to you for free and open access by Scholarly Commons @ Baptist Health South Florida. It has been accepted for inclusion in All Publications by an authorized administrator of Scholarly Commons @ Baptist Health South Florida. For more information, please contact [email protected]. Hindawi Journal of Oncology Volume 2019, Article ID 4047617, 7 pages https://doi.org/10.1155/2019/4047617 Research Article Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients Diana M. Byrnes ,1 Fernando Vargas,2 Christopher Dermarkarian ,3 Ryan Kahn,3 Deukwoo Kwon,4,5 Judith Hurley,5,6 and Jonathan H. Schatz 5,6 1 Hematology-Oncology Fellowship Program, Department of Medicine, Jackson Memorial Hospital, USA 2Miami Cancer Institute, Baptist Health South Florida, USA 3University of Miami Miller School of Medicine, USA 4Biostatistics and Bioinformatics Core, USA 5Sylvester Comprehensive Cancer Center, USA 6Division of Hematology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA Correspondence should be addressed to Jonathan H. Schatz; [email protected] Received 11 January 2019; Revised 26 March 2019; Accepted 11 April 2019; Published 2 May 2019 Guest Editor: Riccardo Masetti Copyright © 2019 Diana M. Byrnes et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acute lymphoblastic leukemia and other aggressive lymphoid malignancies like Burkitt leukemia/lymphoma have high incidence of central nervous system (CNS) involvement. Various solid tumors, most notably breast cancer, can also metastasize into the CNS as a late stage complication causing devastating efects. Intrathecal (IT) chemotherapy consisting of methotrexate, cytarabine, or the two in combination is frequently used for the prophylaxis and treatment of CNS metastasis. Because of the high toxicity of these chemotherapeutic agents, however, their side efect profles are potentially catastrophic. Te incidence of neurotoxicity secondary to IT chemotherapy is well defned in the pediatric literature but is poorly reported in adults. Here, we investigated the incidence of neurologic and nonneurologic side efects secondary to IT chemotherapy in 109 consecutive adult patients over a two-year time period at hospitals associated with our institution. Of 355 IT chemotherapytreatments received by these patients, 11 (3.10%) resulted in paresthesias or paralysis, which we defned as signifcant neurologic events in our analysis. We also examined minor events that arose afer IT chemotherapy, including back pain, headache, fever, vomiting, and asthenia. At least one of these occurred afer 30.70% of IT chemotherapy doses. Clinicians involved in the care of patients receiving IT chemotherapy should be aware of these fndings and consider treatment options lower rate of neurotoxicity such as high-dose systemic methotrexate. 1. Introduction approved for intrathecal use in the United States include methotrexate, cytarabine, liposomal cytarabine, and thiotepa Advances in the treatment of many hematological and solid [1, 5, 6]. Te scheduling and dosing of these medications tumor malignancies have improved disease-free survival varies depending on whether they are used for prophylaxis rates. Unfortunately, such improvements have come with or treatment. Corticosteroids are frequently included with IT increased frequency of relapses in the leptomeninges or CNS chemotherapy, most commonly hydrocortisone, to increase parenchyma, most commonly in aggressive lymphoid malig- cytotoxicity and to decrease the risk of chemical arachnoiditis nancies such as acute lymphoblastic leukemia (ALL), Burkitt [1]. Most prophylactic regimens for leukemia and lymphomas lymphoma/leukemia, and lymphoblastic lymphoma [1–4]. contain methotrexate, either as a single agent or in combina- Leptomeningeal metastasis can also complicate solid tumors, tion with cytarabine. breast carcinoma being the most commonly associated [5]. Te goal of IT chemotherapy is to maximize CNS drug Several treatments have been developed to target malignant exposure through direct CSF introduction, while reduc- cells in the CNS to prevent these events, most commonly ing systemic drug toxicities [2]. Te narrow therapeutic intrathecal (IT) chemotherapy. Te chemotherapeutic agents index and high potential toxicities of these agents mean 2 Journal of Oncology IT administration can have potentially catastrophic conse- our Institutional Review Board. Any information that might quences. Chemical arachnoiditis, an acute syndrome occur- lead to the identifcation of individual patients has been ring hours afer injection and characterized by headache, excluded. All procedures followed were in accordance with backache, vomiting, fever, meningismus, and cerebral fuid the ethical standards of the responsible committee on human pleocytosis, is among the most common and potentially experimentation (institutional and national) and with the serious efects [1, 7]. More severe symptoms also have been Helsinki Declaration of 1975, as revised in 2008. reported including cauda equina syndrome, encephalitis, papilledema, myelopathy, paraplegia, cranial nerve palsies, and seizures [7–11]. It is possible that the incidence of 3. Results neurological complications in this setting is underestimated 3.1. Illustrative Case, Severe Neurologic Complications of IT because cases may go unrecognized or unreported. To Chemotherapy. A 61-year-old Hispanic woman with a history better characterize the incidence of neurological compli- of stage IV difuse large B-cell lymphoma (DLBCL) was cations secondary to IT therapy, we examined sequential admitted for salvage therapy with rituximab, dexametha- adult patients who received it over a two-year period sone, high-dose cytarabine, and cisplatin (R-DHAP). She at our institution. We documented signs and symptoms previously had completed six cycles of rituximab, cyclophos- of neurotoxicity not present before administration that phamide, adriamycin, vincristine, and prednisone (R-CHOP) developed acutely thereafer. We provide illustrative case with twelve milligrams of intrathecal (IT) methotrexate examplefollowedbyanalysisofeventsin109consecutive (MTX) prophylactically in each cycle. patients. On day 1 of R-DHAP the patient received IT MTX 12 mg with cytarabine 50 mg. Flow cytometry and cytology from the 2. Methods lumbar puncture were negative for malignancy. Te following We included adult patients with hematologic and solid day the patient complained of a nonpositional headache rated tumors who received IT chemotherapy between January as 7 out of 10 in intensity. Te headache was associated with 2014 and December 2015 at Jackson Memorial Hospital and photophobia, nausea without vomiting, and double vision. Sylvester Comprehensive Cancer Center. Primary endpoint She denied neck stifness or fever. Acetaminophen did not studied was development of new symptoms indicative of relieve the pain but sumatriptan provided mild relief. On neurotoxicity and/or arachnoiditis within fourteen days of day three she reported bilateral lower extremity weakness, administration of IT chemotherapy, specifcally paralysis, right greater than lef. She also reported inability to ambulate paresthesias, headache, back pain/nuchal rigidity, asthenia, secondary to the weakness, rectal incontinence, and urinary fever, nausea, or vomiting. Additional sensory and sphincter retention. Weakness progressed in the days that followed to disturbances, which may also be associated with arach- bilateral lower extremity paralysis. noiditis, were not reliably documented and were excluded Neurologic exam was signifcant for right lateral rectus from analysis. We defned paralysis and paraesthesias as paresis (with the rest of the cranial nerve exam unre- signifcant neurologic events for the purposes of analysis markable), decreased strength of all muscle groups in the and the other side efects as minor events. Tis division bilateral lower extremities, diminished refexes in the bilateral was to allow distinction between more serious neurologic patellar and Achilles tendons, positive Babinski on the right, toxicities associated with IT chemotherapy from events with and diminished sensation to light touch over the sacrum, less impact on quality of life and/or of a more systemic posterior thighs, and perineum. Te physical exam fndings nature. were not present prior to administration of IT chemother- Known CNS involvement was defned as follows: (1) CSF apy. Six days afer symptom onset repeat LP again yielded positive for malignancy by cytology and/or fow cytometry negative cerebrospinal fuid (CSF) studies for involvement by from samples collected at the time of administration or malignant cells. CSF total protein
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