Immunodeficiency-associated primary CNS lymphomas: an International Primary CNS Lymphoma Collaborative Group study
Abstract
Abstract Immunodeficiency-associated primary central nervous system lymphoma (ID-PCNSL) represents a clinicopathologically distinct PCNSL subtype, for which large studies and prognostic models are lacking. To address this gap, the International PCNSL Collaborative Group conducted a retrospective multicenter study, integrating clinical, radiological, and pathological data from 308 ID-PCNSL cases, diagnosed at 23 participating sites in 7 countries. Preexisting immunodeficiency included administration of immunosuppressants for transplantation (41.2%) or autoimmunity (36.7%) and HIV infection (21.7%). All tumors were diffuse large B-cell lymphomas, with Epstein-Barr virus (EBV) detected in 79.2%. Immune reconstitution together with rituximab and methotrexate–based chemotherapy was associated with the highest response rates and prolonged progression-free survival, irrespective of immunodeficiency subtype and EBV status. Survival outcomes were highly variable, with a 54-month median overall survival. Multivariable Cox regression identified age (per year increment; hazard ratio [HR], 1.05 (95% confidence interval [CI], 1.02-1.07); P< .001), Karnofsky performance status (KPS) <70 (HR, 3.10; 95% CI, 1.67-5.87; P< .001), and EBV positivity (HR, 3.26; 95% CI, 1.47-7.33; P = .004) as prognostic factors for overall survival. A prognostic score was developed based on the sum of these adverse variables (age >60 years, KPS <70, EBV positivity). Stratification by this score yielded median survival times of 135, 29, and 3 months in patients with up to 1, 2, and 3 unfavorable markers (P< .0001). It allowed improved prognostic stratification of ID-PCNSL as compared with the Memorial Sloan Kettering Cancer Center and International Extranodal Lymphoma Study Group models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiological features of ID-PCNSL and introduces a prognostic system with potential to guide future management.
Article Details
Authors (44)
Leon D. Kaulen
1Department of Neurology and European Center for Neurooncology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany
Lakshmi Nayak
4Department of Medical Oncology, Center for Neuro Oncology, Dana Farber Cancer Institute, Boston, MA
Philipp Karschnia
Imke Kraai
6Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Daniela Galluzzo
7Department of Neurology, Yale School of Medicine, New Haven, CT
Fleur A. de Groot
8Department of Hematology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
Matthew Witterholt
9HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Laura Donovan
10Department of Neuro-Oncology, Columbia University Irving Medical Center, New York, NY
Sita Bhella
Luis P. Kuschel
12Department of Neurosurgery, Ludwig Maximilian University, Munich, Germany
Christopher P. Fox
13Department of Haematology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
Sabine Seidel
14Department of Neurology, Knappschaft Kliniken University Hospital Bochum, Ruhr University Bochum, Bochum, Germany
James Paterson
BP Innovation & Engineering
Benjamin Richter
16Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience, Heidelberg University, Mannheim, Germany
Karan S. Dixit
18Division of Neuro-Oncology, Department of Neurology, Feinberg School of Medicine Northwestern University, Chicago, IL
Thomas Zeyen
Juan Pablo Alderuccio
20Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
Silvia Montoto
21Department of Haemato-Oncology, St. Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom
Outi Kuittinen
22Faculty of Health Medicine, School of Medicine, Institute of Clinical Medicine Oncology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
Benjamin-Leon Traub
1Department of Neurology and European Center for Neurooncology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany
Sofia Doubrovinskaia
1Department of Neurology and European Center for Neurooncology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany
Hannah Rohdjess
Katharina J. Müller
23Department of Neurology, Ludwig Maximilian University, Munich, Germany
Roelien Enting
24Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Jeroen de Bresser
Hanne Kuitunen
26Department of Oncology, Cancer Centre, Oulu University Hospital, Oulu, Finland
Fabio M. Iwamoto
10Department of Neuro-Oncology, Columbia University Irving Medical Center, New York, NY
Alvaro Alencar
20Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
Ulrich Herrlinger
Michael Platten
Kate Cwynarski
15Department of Haematology, University College London, London, United Kingdom
Joe Mendez
27Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Patrick Roth
Louisa von Baumgarten
12Department of Neurosurgery, Ludwig Maximilian University, Munich, Germany
Anca Prica
Princess Margaret Cancer Centre, Toronto
Govind Bhagat
Kathryn Lurain
9HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
David Schiff
31Department of Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, VA
Joost S. P. Vermaat
8Department of Hematology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
Joachim M. Baehring
7Department of Neurology, Yale School of Medicine, New Haven, CT
Marcel Nijland
Jorg Dietrich
3Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Tracy T. Batchelor
Wolfgang Wick