Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study

Adam S Zayac; Andrew M Evens; Alexey Danilov; Stephen D Smith; Deepa Jagadeesh; Lori A Leslie; Catherine Wei; Seo-Hyun Kim; Seema Naik; Suchitra Sundaram; Nishitha Reddy; Umar Farooq; Vaishalee P Kenkre; Narendranath Epperla; Kristie A Blum; Nadia Khan; Daulath Singh; Juan P Alderuccio; Amandeep Godara; Catherine Diefenbach; Emma Rabinovich; Gaurav Varma; Reem Karmali; Yusra Shao; Asaad Trabolsi; Madelyn Burkart; Peter Martin; Sarah Stettner; Ayushi Chauhan; Yun Kyong Choi; Allandria Straker-Edwards; Andreas Klein; Michael C Churnetski; Kirsten M Boughan; Stephanie Berg; Bradley M Haverkos; Victor M Orellana-Noia; Christopher D'Angelo; David A Bond; Seth M Maliske; Ryan Vaca; Gabriella Magarelli; Amy Sperling; Max J Gordon; Kevin A David; Malvi Savani; Paolo Caimi; Manali Kamdar; Matthew A Lunning; Neil Palmisiano; Parameswaran Venugopal; Craig A Portell; Veronika Bachanova; Tycel Phillips; Izidore S Lossos; Adam J Olszewski

doi:10.3324/haematol.2020.270876

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Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study

Journal article

Open access

Peer reviewed

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study

Adam S Zayac, Andrew M Evens, Alexey Danilov, Stephen D Smith, Deepa Jagadeesh, Lori A Leslie, Catherine Wei, Seo-Hyun Kim, Seema Naik, Suchitra Sundaram, …

Haematologica (Roma), Vol.106(7), pp.1932-1942

07/01/2021

DOI: 10.3324/haematol.2020.270876

PMCID: PMC8252937

PMID: 33538152

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Abstract

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Adolescent

Adult

Aged

Aged, 80 and over

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Burkitt Lymphoma - diagnosis

Burkitt Lymphoma - drug therapy

Burkitt Lymphoma - epidemiology

Central Nervous System

Central Nervous System Neoplasms - diagnosis

Central Nervous System Neoplasms - drug therapy

Central Nervous System Neoplasms - epidemiology

Cohort Studies

Cyclophosphamide - therapeutic use

Disease-Free Survival

Doxorubicin - therapeutic use

HIV Infections

Humans

Middle Aged

Neoplasm Recurrence, Local

Rituximab - therapeutic use

Young Adult

Details

Title: Subtitle: Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study
Creators: Adam S Zayac - Brown University
Andrew M Evens - Robert Wood Johnson University Hospital
Alexey Danilov - Oregon Health & Science University
Stephen D Smith - Fred Hutch Cancer Center
Deepa Jagadeesh - Cleveland Clinic
Lori A Leslie - Hackensack University Medical Center
Catherine Wei - Robert Wood Johnson University Hospital
Seo-Hyun Kim - Rush University Medical Center
Seema Naik - Pennsylvania State University
Suchitra Sundaram - Roswell Park Cancer Institute
Nishitha Reddy - Vanderbilt University Medical Center
Umar Farooq - University of Iowa
Vaishalee P Kenkre - University of Wisconsin–Madison
Narendranath Epperla - The Ohio State University
Kristie A Blum - Emory University
Nadia Khan - Fox Chase Cancer Center
Daulath Singh - Loyola University Medical Center
Juan P Alderuccio - University of Miami
Amandeep Godara - Tufts Medical Center
Catherine Diefenbach - New York University
Emma Rabinovich - University of Illinois Chicago
Gaurav Varma - Cornell University
Reem Karmali - Northwestern University
Yusra Shao - Cleveland Clinic
Asaad Trabolsi - University of Miami
Madelyn Burkart - Northwestern University
Peter Martin - Cornell University
Sarah Stettner - University of Illinois Chicago
Ayushi Chauhan - Georgetown University
Yun Kyong Choi - New York University
Allandria Straker-Edwards - Fox Chase Cancer Center
Andreas Klein - Tufts Medical Center
Michael C Churnetski - Emory University
Kirsten M Boughan - University Hospitals of Cleveland
Stephanie Berg - Loyola University Medical Center
Bradley M Haverkos - University of Colorado Boulder
Victor M Orellana-Noia - University of Virginia
Christopher D'Angelo - University of Wisconsin–Madison
David A Bond - The Ohio State University
Seth M Maliske - University of Iowa
Ryan Vaca - Pennsylvania State University
Gabriella Magarelli - Hackensack University Medical Center
Amy Sperling - Fred Hutch Cancer Center
Max J Gordon - Oregon Health & Science University
Kevin A David - Robert Wood Johnson University Hospital
Malvi Savani - University of Minnesota
Paolo Caimi - University Hospitals of Cleveland
Manali Kamdar - University of Colorado Boulder
Matthew A Lunning - University of Nebraska Medical Center
Neil Palmisiano - Thomas Jefferson University
Parameswaran Venugopal - Rush University Medical Center
Craig A Portell - University of Virginia
Veronika Bachanova - University of Minnesota
Tycel Phillips - University of Michigan
Izidore S Lossos - University of Miami
Adam J Olszewski - Brown University
Resource Type: Journal article
Publication Details: Haematologica (Roma), Vol.106(7), pp.1932-1942
DOI: 10.3324/haematol.2020.270876
PMID: 33538152
PMCID: PMC8252937
NLM abbreviation: Haematologica
ISSN: 1592-8721
eISSN: 1592-8721
Grant note: KL2 TR002534 / NCATS NIH HHS
Language: English
Date published: 07/01/2021
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359589302771

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