Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

Victor Manuel Orellana-Noia, Daniel R. Reed, Ashley Alesia McCook, Jeremy Michael Sen, Christian M. Barlow, Mary Kate Malecek, Marcus Watkins, Brad S. Kahl, Michael A. Spinner, Ranjana Advani, Timothy J. Voorhees, Anson Snow, Natalie Sophia Grover, Amy Ayers, Jason Romancik, Yuxin Liu, Scott F. Huntington, Julio C. Chavez, Hayder Saeed, Aleksandr LazaryanVikram Raghunathan, Stephen E. Spurgeon, Thomas A. Ollila, Christopher Del Prete, Adam Olszewski, Emily C. Ayers, Daniel J. Landsburg, Benjamin Echalier, Jun Lee, Manali Kamdar, Paolo F. Caimi, Timothy Fu, Jieqi Liu, Kevin A. David, Hanan Alharthy, Jennie Law, Reem Karmali, Harsh Shah, Deborah M. Stephens, Ajay Major, Alexandra E. Rojek, Sonali M. Smith, Amulya Yellala, Avyakta Kallam, Shazi Nakhoda, Nadia Khan, Mohammad Ahsan Sohail, Brian T. Hill, Odeth Barrett-Campbell, Frederick Lansigan, Jeffrey Switchenko, Jonathon Cohen, Craig A. Portell

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Original languageEnglish (US)
Pages (from-to)413-423
Number of pages11
Issue number3
StatePublished - Jan 20 2022

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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