Immunodeficiency-associated primary CNS lymphomas: An International Primary CNS Lymphoma Collaborative Group (IPCG) Study

Immunodeficiency-associated primary CNS 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 an international retrospective multi-center study, integrating clinical, radiological, and pathological data from 308 ID-PCNSL, diagnosed at 23 participating sites in 7 countries. Pre-existing 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-methotrexate-(RM)-based chemotherapy was associated with 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 HR: 1.05 (95%-CI:1.02-1.07); p < 0.001), Karnofsky Performance status (KPS) < 70 (HR: 3.10 (95%-CI:1.67-5.87); p < 0.001), EBV positivity (HR: 3.26 (95%-CI:1.47-7.33); p = 0.004) as prognostic factors for OS. 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 one, two and three unfavorable markers (p < 0.0001). It allowed improved prognostic stratification of ID-PCNSL as compared to the well-established MSKCC and IELSG models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiologic features of ID-PCNSL and introduces an easily applicable prognostic system with potential to guide future management.

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Journal
Blood
Published
2026-03-17
DOI
https://doi.org/10.1182/blood.2025031869
Primary Topic
CNS Lymphoma Diagnosis and Treatment
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article
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article

Immunodeficiency-associated primary CNS lymphomas: An International Primary CNS Lymphoma Collaborative Group (IPCG) Study

Silvia Montoto, Joe Sammy Mendez, Kathryn Lurain, U. Herrlinger et al.
Blood
CNS Lymphoma Diagnosis and Treatment
article

Immunodeficiency-associated primary CNS lymphomas: An International Primary CNS Lymphoma Collaborative Group (IPCG) Study

Silvia Montoto, Joe Sammy Mendez, Kathryn Lurain, U. Herrlinger, Outi Kuittinen, Marcel Nijland, Louisa von Baumgarten, Anca A. Prica, Jeroen de Bresser, I.H. Kraai, Karan Dixit, Leon D. Kaulen, Roelien H. Enting, James Paterson, Luis P. Kuschel, Thomas Zeyen, Sita Bhella, Juan Pablo Alderuccio, Hanne Kuitunen, Christopher P. Fox, FABIO MASSAITI IWAMOTO, Sabine Seidel, Benjamin Richter, L. Nayak, Benjamin-Leon Traub, Matthew Witterholt, Alvaro J. Alencar, K Mueller, Wolfgang Wick, Kate Cwynarski, Daniela Raffaela Galluzzo, Laura Donovan, Sofia Doubrovinskaia, Joost SP Vermaat, Jörg Dietrich, Joachim Baehring, Tracy T Batchelor, Patrick Roth, David Schiff, Govind Bhagat, Fleur A de Groot, Michael Platten, Philipp Karschnia, Hannah Rohdjess
article en

Abstract

Immunodeficiency-associated primary CNS 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 an international retrospective multi-center study, integrating clinical, radiological, and pathological data from 308 ID-PCNSL, diagnosed at 23 participating sites in 7 countries. Pre-existing 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-methotrexate-(RM)-based chemotherapy was associated with 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 HR: 1.05 (95%-CI:1.02-1.07); p < 0.001), Karnofsky Performance status (KPS) < 70 (HR: 3.10 (95%-CI:1.67-5.87); p < 0.001), EBV positivity (HR: 3.26 (95%-CI:1.47-7.33); p = 0.004) as prognostic factors for OS. 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 one, two and three unfavorable markers (p < 0.0001). It allowed improved prognostic stratification of ID-PCNSL as compared to the well-established MSKCC and IELSG models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiologic features of ID-PCNSL and introduces an easily applicable prognostic system with potential to guide future management.

Blood
Northwestern University (US), Brigham and Women's Hospital (US), National Institutes of Health (US), University Health Network (CA), University Medical Center Groningen (NL), University College London Hospitals NHS Foundation Trust (GB), Harvard University (US), University of Nottingham (GB), University of Miami (US), Emory University (US), University of Groningen (NL), University of Mannheim (DE), German Cancer Research Center (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), University of Zurich (CH), University of Utah (US), Heidelberg University (DE), Barts Health NHS Trust (GB), Oulu University Hospital (FI), University Hospital Bonn (DE), Leiden University Medical Center (NL), CHI Health Creighton University Medical Center - Bergan Mercy (US), University Hospital Heidelberg (DE), Princess Margaret Cancer Centre (CA), LMU Klinikum (DE), Yale University (US), Massachusetts General Hospital (US), Kuopio University Hospital (FI), Bernstein Center for Computational Neuroscience Heidelberg-Mannheim (DE), Dana-Farber Cancer Institute (US), National Cancer Institute (US), University Medical Centre Mannheim (DE), Sylvester Comprehensive Cancer Center (US), University College London (GB), Saint Louis University (US), University of Virginia (US), The Ohio State University (US), Ludwig-Maximilians-Universität München (DE), Ruhr University Bochum (DE), University of Oulu (FI)
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Openalex Percentile: Top 27%
CNS Lymphoma Diagnosis and Treatment
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