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Limited efficacy of high-dose methotrexate in patients with neurolymphomatosis

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Abstract

Neurolymphomatosis (NL) is a rare manifestation of non-Hodgkin lymphoma, in which malignant cells infiltrate the peripheral nerves. Most patients are treated with high-dose methotrexate (HD-MTX)-based systemic chemotherapy regimens similar to patients with central nervous system lymphoma. However, because NL is rare, the efficacy of HD-MTX is largely unknown. We reviewed medical records of patients diagnosed with NL over the past 10 years and identified 18 patients. The underlying hematological malignancy was diffuse large B-cell lymphoma (DLBCL) in 10 patients (55.6%), intravascular large B-cell lymphoma in six (33.3%), and other types in two patients. Ten patients were treated with HD-MTX-based systemic chemotherapy; the response rates with and without HD-MTX-based chemotherapy were 100% (n = 10) and 85.7% (n = 6), respectively (P = 0.41). The median progression-free and overall survival rates of patients with versus without HD-MTX treatment were 6.4 vs. 8.5 months (P = 0.97) and 13.5 vs. 8.5 months (P = 0.63), respectively. Despite the initial favorable responses, rapid disease recurrence was observed in most patients administered HD-MTX-based chemotherapy. Our observations suggest that HD-MTX-based chemotherapy may have insufficient efficacy against NL, and that other therapeutic approaches are required to improve the outcomes of patients with this rare disease.

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References

  1. Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH. Neurolymphomatosis. Neuro Oncol. 2003;5:104–15.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Matsue K, Hayama BY, Iwama K, Koyama T, Fujiwara H, Yamakura M, et al. High frequency of neurolymphomatosis as a relapse disease of intravascular large B-cell lymphoma. Cancer. 2011;117:4512–21.

    Article  PubMed  Google Scholar 

  3. Maravilla KR, Bowen BC. Imaging of the peripheral nervous system: evaluation of peripheral neuropathy and plexopathy. Am J Neuroradiol. 1998;19:1011–23.

    PubMed  CAS  Google Scholar 

  4. Swarnkar A, Fukui MB, Fink DJ, Rao GR. MR imaging of brachial plexopathy in neurolymphomatosis. Am J Roentgenol. 1997;169:1189–90.

    Article  CAS  Google Scholar 

  5. Byun JM, Kim KH, Kim M, Kim TM, Jeon YK, Park JH, et al. Diagnosis of secondary peripheral neurolymphomatosis: a multi-center experience. Leuk Lymphoma. 2017;58:2624–32.

    Article  PubMed  Google Scholar 

  6. Shree R, Goyal MK, Modi M, Gaspar BL, Radotra BD, Ahuja CK, et al. The diagnostic dilemma of neurolymphomatosis. J Clin Neurol. 2016;12:274–81.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kinoshita H, Yamakado H, Kitano T, Kitamura A, Yamashita H, Miyamoto M, et al. Diagnostic utility of FDG-PET in neurolymphomatosis: report of five cases. J Neurol. 2016;263:1719–26.

    Article  PubMed  Google Scholar 

  8. Gan HK, Azad A, Cher L, Mitchell PL. Neurolymphomatosis: diagnosis, management, and outcomes in patients treated with rituximab. Neuro Oncol. 2010;12:212–5.

    Article  PubMed  Google Scholar 

  9. Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D, et al. Neurolymphomatosis: an international primary CNS lymphoma collaborative group report. Blood. 2010;115:5005–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Ghobrial IM, Buadi F, Spinner RJ, Colgan JP, Wolanskyj AP, Dyck PJ, et al. High-dose intravenous methotrexate followed by autologous stem cell transplantation as a potentially effective therapy for neurolymphomatosis. Cancer. 2004;100:2403–7.

    Article  PubMed  CAS  Google Scholar 

  11. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009;374:1512–20.

    Article  PubMed  CAS  Google Scholar 

  12. Stamatoullas A, Fruchart C, Bastit D, Boulet D, Moncondult M, Piguet H, et al. Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. Cancer. 1996;77:2302–7.

    Article  PubMed  CAS  Google Scholar 

  13. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  PubMed  CAS  Google Scholar 

  14. Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010;51:1523–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Kantarjian HM, O’Brien S, Smith TL, Cortes J, Giles FJ, Beran M, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547–61.

    Article  PubMed  CAS  Google Scholar 

  16. Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516—the Southwest Oncology Group. J Clin Oncol. 2009;27:114–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kim SJ, Oh SY, Kim JS, Kim H, Lee GW, Won JH, et al. Secondary central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma: a therapeutic dilemma. Ann Hematol. 2011;90:539–46.

    Article  PubMed  CAS  Google Scholar 

  18. Abramson JS, Hellmann M, Barnes JA, Hammerman P, Toomey C, Takvorian T, et al. Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer. 2010;116:4283–90.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan

    Hiroki Kobayashi, Yoshiaki Abe, Daisuke Miura, Kentaro Narita, Akihiro Kitadate, Masami Takeuchi & Kosei Matsue

Authors
  1. Hiroki Kobayashi
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  2. Yoshiaki Abe
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  3. Daisuke Miura
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  4. Kentaro Narita
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  5. Akihiro Kitadate
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  6. Masami Takeuchi
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  7. Kosei Matsue
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Contributions

HK and KM planned and designed the study, collected the data, and wrote the manuscript. HK, KM, YA, DM, KN, AK, and MT performed patient care activities. All authors reviewed the manuscript.

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Correspondence to Hiroki Kobayashi.

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The authors declare no competing financial interests.

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All procedures involving human participants in this study were in accordance with the ethical standards of the institutional and national research committee as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Kobayashi, H., Abe, Y., Miura, D. et al. Limited efficacy of high-dose methotrexate in patients with neurolymphomatosis. Int J Hematol 109, 286–291 (2019). https://doi.org/10.1007/s12185-018-02586-7

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  • DOI: https://doi.org/10.1007/s12185-018-02586-7

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