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Safety of intra-cerebrospinal fluid chemotherapy in onco-haematological patients: a retrospective analysis of 627 interventions

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Abstract

Intra-cerebrospinal fluid chemotherapy (ICC) is used widely to treat or prevent neoplastic meningitis (NM), although its safety has not been thoroughly assessed. We aimed to analyse the incidence, severity and cause of the adverse reactions provoked by ICC in a cohort of onco-haematological patients. We retrospectively reviewed all the adverse reactions related to ICC procedures performed by the same researcher over a 5-year period. We classified them according to their severity and cause, and examined their association with certain characteristics of the patients and interventions. A total of 627 procedures were performed on 124 patients, in which 59 adverse reactions were documented (9.4 %). Thirty-two (54 %) of these were considered severe and 30 (51 %) were due to the drug itself. NM was associated with a higher incidence of adverse reactions (p = 0.002) and severe adverse reactions (p < 0.001). Adverse reactions were more common (p = 0.028) and more often severe (p = 0.008) when an Ommaya reservoir was used, as opposed to the lumbar puncture procedure. The use of liposomal cytarabine was also associated with a higher incidence of adverse reactions (p < 0.001) and serious adverse reactions (p < 0.001) than immediate-release drugs. Liposomal cytarabine provoked more adverse reactions attributable to the drug when administered by lumbar puncture (p = 0.192), whereas the remaining drugs had higher risk when administered via Ommaya reservoir (p = 0.015). ICC seems a relatively safe procedure. Adverse reactions appear to be more frequent when NM is already present. Lumbar puncture seems to be safer than the Ommaya reservoir, except when liposomal cytarabine is administered.

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References

  1. Enting RH (2005) Leptomeningeal neoplasia: epidemiology, clinical presentation, CSF analysis and diagnostic imaging. Cancer Treat Res 125:17–30

    Article  PubMed  Google Scholar 

  2. Subira D, Serrano C, Castañón S et al (2012) Role of flow cytometry immunophenotyping in the diagnosis of leptomeningeal carcinomatosis. Neuro Oncol 14:1–10

    Article  Google Scholar 

  3. SundaresanN Suite ND (1989) Optimal use of the Ommaya reservoir in clinical oncology. Oncology (Williston Park) 3:15–22

    Google Scholar 

  4. Glantz M, Jaeckle A, Chamberlain MC (1999) A randomized controlled trial comparing intrathecal sustained release cytarabine (Depocyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 5:3394–3402

    CAS  PubMed  Google Scholar 

  5. Shapiro WR, Schmid M, Glantz M (1999) A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic lymphomatous meningitis. J Clin Oncol 17:3110–3116

    PubMed  Google Scholar 

  6. Boogerd W, Van den Bent MJ, Koehler PJ et al (2004) The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomized study. Eur J Cancer 40:2726–2733

    Article  CAS  PubMed  Google Scholar 

  7. Gökbuget N, Hartog CM, Bassan R et al (2011) Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma. Haematologica 96:238–244

    Article  PubMed Central  PubMed  Google Scholar 

  8. Rubenstein JL, Li J, Chen I et al (2013) Multicenter phase I trial of intraventricular immuno-chemotherapy in recurrent CNS lymphoma. Blood 121:745–751

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. National Cancer Institute (2010) Common terminology criteria for adverse events, version 4.0. Washington, DC: National Cancer Institute, National Institutes of Health, Department of Health and Human Services; May 28, 2009 (v4.03: June 14, 2010). National Institutes of Health publication 09-5410

  10. Naranjo CA, Busto U, Sellers E et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245

    Article  CAS  PubMed  Google Scholar 

  11. Council for International Organization of Medical Sciences (1995) Guidelines for preparing core clinical safety data information of drugs. Report of CIOMS Working Group III. CIOMS, Geneva

    Google Scholar 

  12. Evans RW, Armon C, Frohman EM, Goodin DS (2000) Assessment: prevention of post-lumbar puncture headaches: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 55:909–914

    Article  CAS  PubMed  Google Scholar 

  13. Pavón A, Anadón-Senac P (2001) Neurotoxicidad de lidocaína intratecal. Rev Esp Anestesiol Reanim 48:626–636

    Google Scholar 

  14. Burstein R, Yamamura H, Malick A, Strassman AM (1998) Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 79:964–982

    CAS  PubMed  Google Scholar 

  15. Vázquez R, Johnson D, Ahmed S (2011) Epidural blood patch for postdural position postural vertigo. Pain Med 12:148–151

    Article  PubMed  Google Scholar 

  16. Siegman-Igra Y, Bar-Yosef S, Gorea A, Avram J (1993) Nosocomial acinetobacter meningitis secondary to invasive procedures: report of 25 cases and review. Clin Infect Dis 17:843–849

    Article  CAS  PubMed  Google Scholar 

  17. Lyke KE, Obasanjo OO, Williams MA, O’Brien M, Chotani R, Perl TM (2001) Ventriculitis complicating use of intraventricular catheters in adult neurosurgical patients. Clin Infect Dis 33:2028

    Article  CAS  PubMed  Google Scholar 

  18. Ratcheson RA, Ommaya A (1968) Experience with the subcutaneous cerebrospinal fluid reservoir—preliminary report of 60 cases. N Engl J Med 279:1025–1031

    Article  CAS  PubMed  Google Scholar 

  19. Portella G, Cormio M, Citerio G et al (2002) Continuous cerebral compliance monitoring in severe head injury: its relationship with intracranial pressure and cerebral perfusion pressure. Acta Neurochir Suppl 81:173–175

    CAS  PubMed  Google Scholar 

  20. García-Tena J, López-Andreu JA, Ferrís J et al (1995) Intrathecal chemotherapy-related myeloencephalopathy in a young child with acute lymphoblastic leukemia. Pediatr Hematol Oncol 12:377–385

    Article  PubMed  Google Scholar 

  21. Gabay M, Takkar J, Stachnik J, Woelik S, Villano J (2012) Intra-CSF administration of chemotherapy medications. Cancer Chemother Pharmacol 70:1–15

    Article  CAS  PubMed  Google Scholar 

  22. Kim J, Kim S, Nam D, Lee J, Park K, Kong D (2011) Leukoencephalopathy and disseminated necrotizing leukoencephalopathy following intrathecal methotrexate chemotherapy and radiation therapy for central nerve system lymphoma or leukemia. J Korean Neurosurg Soc 50:304–310

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Pardo J, Ruiz-Ocaña C, González-Cortijo L, Alaez-Usón C (2010) Route of intracerebrospinal fluid liposomal cytarabine administration, safety and efficacy of therapy in neoplastic meningitis [abstract]. Neuro Oncol 12(Suppl 3):57

    Google Scholar 

  24. Gállego Pérez-Larraya J, Palma JA, Carmona-Iraqui M et al (2011) Neurological complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma. J Neurooncol 103:603–609

    Article  PubMed  Google Scholar 

  25. Young GA, Militen S, Jurd J, Poulgrain P, Vincent PC (1986) The intraventricular reservoir in the treatment of neurological disease secondary to hematological malignancy: an eight year experience. Aust N Z J Med 16:373–377

    Article  CAS  PubMed  Google Scholar 

  26. Browne MJ, Dinndorf PA, Perek D et al (1987) Infectious complications of intraventricular reservoirs in cancer patients. Pediatr Infect Dis J 6:182–189

    Article  CAS  PubMed  Google Scholar 

  27. Peyrl A, Chocholous M, Azizi AA et al (2014) Safety of Ommaya reservoirs in children with brain tumors: a 20-year experience with 5472 intraventricular drug administration in 98 patients. J Neurooncol 120:139–145

    Article  CAS  PubMed  Google Scholar 

  28. Chamberlain MC, Kormanik PA, Barba D (1997) Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. J Neurosurg 87:694–699

    Article  CAS  PubMed  Google Scholar 

  29. Zairi F, Le Rhun E, Bertrand N et al (2015) Complications related to the use of an intraventricular access device for the treatment of leptomeningeal metastases from solid tumor: a single centre experience in 112 patients. J Neurooncol. doi:10.1007/s1060-015-1842-x

    PubMed  Google Scholar 

  30. Olson ME, Chernik NL, Posner JB (1974) Infiltration of the leptomeninges by systemic cancer. A clinical and pathologic study. Arch Neurol 30:122–137

    Article  CAS  PubMed  Google Scholar 

  31. Illán J, Simo M, Serrano C et al (2014) Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma. Transl Res 164:460–467

    Article  PubMed  Google Scholar 

  32. Chamberlain MC, Glantz M, Groves M, Wilson W (2009) Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk and determining benefit of treatment. Semin Oncol 36(4 Suppl2):S35–S45

    Article  PubMed  Google Scholar 

  33. Jurczak W, Kroll-Balcerzak R, Giebel S et al (2015) Liposomal cytarabine in the prophylaxis and treatment of CNS lymphoma: toxicity analysis in a retrospective case series study conducted at Polish Lymphoma Research Group Centers. Med Oncol 32:90

    Article  PubMed Central  PubMed  Google Scholar 

  34. 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

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Allergan, Inc., for their English editorial assistance.

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Authors and Affiliations

  1. Department of Neurology, Hospital Rey Juan Carlos, Universidad Rey Juan Carlos, C/Gladiolo s/n, Móstoles, 28933, Madrid, Spain

    Javier Pardo-Moreno

  2. Department of Preventive Medicine, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Universidad Complutense, Madrid, Spain

    Cristina Fernández

  3. Department of Neurology, Hospital Quirón Madrid, Pozuelo de Alarcón, Madrid, Spain

    Rafael Arroyo

  4. Department of Neurosurgery, Hospital Quirón Madrid, Pozuelo de Alarcón, Madrid, Spain

    Carlos Ruiz-Ocaña

  5. Department of Haematology, Hospital Quirón Madrid, Pozuelo de Alarcón, Madrid, Spain

    Concepción Aláez

  6. Department of Neurology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Universidad Complutense, Madrid, Spain

    Rafael Arroyo & María-Luz Cuadrado

Authors
  1. Javier Pardo-Moreno
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  2. Cristina Fernández
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Correspondence to Javier Pardo-Moreno.

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Pardo-Moreno, J., Fernández, C., Arroyo, R. et al. Safety of intra-cerebrospinal fluid chemotherapy in onco-haematological patients: a retrospective analysis of 627 interventions. J Neurooncol 125, 351–358 (2015). https://doi.org/10.1007/s11060-015-1922-y

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  • DOI: https://doi.org/10.1007/s11060-015-1922-y

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