Immunodeficiency-associated primary CNS lymphomas: an International Primary CNS Lymphoma Collaborative Group study

Kaulen LD, Nayak L, Karschnia P, Kraai I, Galluzzo D, de Groot FA, Witterholt M, Donovan L, Bhella S, Kuschel LP, Fox CP, Seidel S, Paterson J, Richter B, Dixit KS, Zeyen T, Alderuccio JP, Montoto S, Kuittinen O, Traub BL, Doubrovinskaia S, Rohdjess H, Müller KJ, Enting R, de Bresser J, Kuitunen H, Iwamoto FM, Alencar A, Herrlinger U, Platten M, Cwynarski K, Mendez J, Roth P, von Baumgarten L, Prica A, Bhagat G, Lurain K, Schiff D, Vermaat JS, Baehring JM, Nijland M, Dietrich J, Batchelor TT, Wick W (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1182/blood.2025031869

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.

Involved external institutions

Yale University United States (USA) (US) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Ludwig-Maximilians-Universität (LMU) Germany (DE) Harvard University United States (USA) (US) University of Nottingham United Kingdom (GB) Universitätsklinikum Knappschaftskrankenhaus Bochum Germany (DE) Princess Margaret Cancer Centre / Princess Margaret Hospital Canada (CA) Leiden University Medical Center Netherlands (NL) Saint Louis University (SLU) United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) University of Virginia (UVA) United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) Universitätsklinikum Heidelberg Germany (DE) Sylvester Comprehensive Cancer Center United States (USA) (US) University College London (UCL) United Kingdom (GB) Oulu University Hospital Finland (FI) Ruprecht-Karls-Universität Heidelberg Germany (DE) Northwestern University United States (USA) (US) Universitätsklinikum Bonn Germany (DE) St Bartholomew's Hospital United Kingdom (GB) Dana-Farber Cancer Institute United States (USA) (US) University of Utah United States (USA) (US) Universitätsspital Zürich (USZ) Switzerland (CH)

How to cite

APA:

Kaulen, L.D., Nayak, L., Karschnia, P., Kraai, I., Galluzzo, D., de Groot, F.A.,... Wick, W. (2026). Immunodeficiency-associated primary CNS lymphomas: an International Primary CNS Lymphoma Collaborative Group study. Blood. https://doi.org/10.1182/blood.2025031869

MLA:

Kaulen, Leon D., et al. "Immunodeficiency-associated primary CNS lymphomas: an International Primary CNS Lymphoma Collaborative Group study." Blood (2026).

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