Canterbury DHB

Primary CNS Lymphoma

PCNSL comprises 2.7% of all CNS tumours. The incidence is increased in HIV/AIDS and congenital immunodeficiency. The histology is diffuse large B cell lymphoma in 90%. Most patients present with focal neurological deficits. Contrast enhanced MRI is the investigation of choice. Staging investigations should include complete ophthalmology and CSF evaluation. A stereotactic biopsy before corticosteroid therapy is indicated in all patients with suspected PCNSL when delay in treatment is considered safe. Methotrexate based multi-agent chemotherapy is currently the treatment of choice. See Grommes, C. and L.M. DeAngelis (2017). "Primary CNS Lymphoma." J Clin Oncol 35(21):2410-2418.

1. Diagnosis should be confirmed histologically, and preferably by stereotactic brain biopsy.
2. Staging should include: CT chest/abdo/pelvis, testicular USS, LP (protein, glucose, cytology, flow cytometry and IGH), intra-ocular examination with biopsy of lesions, HIV.
3. Prognostic score (age >60, PS >1, raised LDH, raised CSF protein, involvement of deep brain).
4. Warn of risk of neurocognitive deterioration when obtaining treatment consent.
5. Dexamethasone is the treatment of choice for palliation but avoid before biopsy.
6. Whole brain XRT is useful for palliation but not primary treatment in fit patients.
7. There is no role for CHOP-like regimens.
8. All patients should be offered a chemotherapy regimen incorporating high dose IV methotrexate based on an established protocol and ideally within a trial. Dr Samar Issa at Middlemore, Auckland (Samar.Issa@middlemore.co.nz) organises all PCNSL trials and should be contacted in the first instance for advice about the treatment of these patients.
9. Addition of rituximab is helpful. See Birnbaum, T., et al. (2012). "Rituximab significantly improves complete response rate in patients with primary CNS lymphoma." J Neurooncol.
10. Consolidation whole brain XRT should be considered for responding patients.
11. There is no evidence for intrathecal MTX in addition to high dose IV MTX.
12. Autologous transplantation as 1st line therapy is experimental. See:
    • Illerhaus, G., Kasenda, B. (2016). "High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial." Lancet Haematol 3: e388-97.
    • Ferreri, A.J., Cwynarski, K. (2016). "Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial." Lancet Haematol 3: e217-27.
13. Concurrent intra-ocular and CNS lymphoma should be treated with systemic HD-MTX-based chemotherapy followed by radiation to both globes and possibly also the brain if the patient is less than 60 years old. Isolated intra-ocular disease should be treated in the same way. Intra-vitreal MTX is an effective treatment option for patients with recurrent disease confined to the eyes (grade B, level III).

Topic Code: 9648