Systemic HD-MTX for CNS prophylaxis in high-risk DLBCL patients: a prospectively collected, single-center cohort analysis
We evaluated the efficacy of systemic high-dose methotrexate (HD-MTX) for CNS prophylaxis in a prospectively recruited cohort of DLBCL patients at high risk of CNS relapse. High-risk CNS relapse was defined as the involvement of ≥ 2 extranodal sites with elevated lactate dehydrogenase (LDH); CNS international prognostic index (CNS-IPI) ≥ 4; or involvement of high-risk extranodal sites, including bone marrow, breasts, testes, and paranasal sinuses. Overall, 130 patients who received at least two cycles of standard chemoimmunotherapy were evaluated; of these, 64 patients received additional systemic HD-MTX, either on day 15 of alternating cycles or 2–5 weeks after completion of primary therapy. Patients receiving HD-MTX showed a generally higher risk of CNS relapse than the other 66 patients not receiving prophylaxis. The estimated 2-year cumulative CNS relapse, progression-free survival and overall survival rates were 8.1%, 66.3%, and 77.5%, respectively, in patients who received systemic HD-MTX and 6.9%, 67.4%, and 71.4%, respectively, in patients without prophylaxis, with no significant between-group differences. Although this study does not show that systemic HD-MTX is definitively effective, these results may be of help to other researchers investigating the utility of HD-MTX prophylaxis in mitigating negative risk factors.
KeywordsDiffuse large B-cell lymphoma CNS relapse CNS prophylaxis Systemic high dose methotrexate
The authors thank the many patients and their families, as well as the physicians, who made this study possible.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.National Cancer Institute. SEER cancer statistics review, 1975–2009. http://seer.cancer.gov/csr/1975_2009_pops09/. Accessed 10 May 2018.
- 3.Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23:4117–26.CrossRefGoogle Scholar
- 4.Das A, Kundu R, Agarwal R, Ghose A. CNS prophylaxis in diffuse large B cell lymphoma. J Cancer Prev Curr Res. 2016;5:00177.Google Scholar
- 8.Malecek MK, Rozell S, Chu BA, Steve T, Galanina N, Nabhan C, et al. Risk factors for CNS relapse among patients with DLBCL treated with EPOCH-R. Blood. 2015;126:1500.Google Scholar
- 9.Yamamoto W, Tomita N, Watanabe R, Hattori Y, Nakajima Y, Hyo R, et al. Central nervous system involvement in diffuse large B-cell lymphoma. Eur J Haematol. 2010;85:6–10.Google Scholar
- 10.Barosi G, Carella A, Lazzarino M, Marchetti M, Martelli M, Rambaldi A, et al. Management of nodal diffuse large B-cell lymphomas: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica. 2006;91:96–103.Google Scholar
- 11.El-Galaly TC, Villa D, Michaelsen TY, Hutchings M, Mikhaeel NG, Savage KJ, et al. The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma: an international multicenter study of 1532 patients treated with chemoimmunotherapy. Eur J Cancer. 2017;75:195–203.CrossRefGoogle Scholar
- 14.Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009;113:3896–902.CrossRefGoogle Scholar
- 15.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.CrossRefGoogle Scholar
- 23.Goldschmidt N, Horowitz NA, Hefetz V, Darawshy F, Mashiach T, Shaulov A, et al. Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse. Leuk Lymphoma. 2019. https://doi.org/10.1080/10428194.2018.1564823.Google Scholar
- 26.Seo S, Hong JY, Yoon S, Yoo C, Park JH, Lee JB, et al. Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era. Oncotarget. 2016;7:76934–43.Google Scholar