Case 42 – summary

Thank you for all of your input! This time we looked at primary CNS lymphoma in an immunocompetent patient.

Following 4 cycles of treatment with high dose methotrexate and cytarabine our patient had an excellent response on MRI. He went on to have an autologous stem cell transplant with thiotepa, busulfan and cyclophosphamide (TBC) conditioning regime and is doing well.

There have been recent guidelines from the European association for neuro-oncology on the management of primary CNS lymphomas. In addition there has also been a recent phase 2 study (ELSG #32) looking at different treatment regimes in primary CNS lymphoma.

Primary CNS lymphomas (PCNSL) are a relatively rare malignancy accounting for around 1% of all lymphomas, and 3% of all CNS tumours.

Primary CNS DLBCL is tumour(s) which are confined to brain/eyes/meninges/spinal cord, and there must be no evidence of systemic lymphoma.

Treatment of this lymphoma can be challenging, especially when it occurs in elderly patients. Chemotherapy options are limited due to the blood brain barrier and treatment can cause significant neurotoxic side effects, especially in an elderly population.

Presentation of patients will vary depending on the site of disease. 

When diagnosing a patient MRI scan with contrast is the neuroimaging modality of choice. This should also be used to asses response to treatment.

Where PCNSL is suspected a histological diagnosis should be gained to confirm this. This may be done by a stereotactic needle biopsy. Resection of the tumour is not usually indicated unless there is a very large tumour bulk or it is causing herniation, as tumours can be multi focal, and microscopic areas are likely to be left behind.

When working up a patient, an LP to look for malignant cells, and ophthalmology assessment with slit lamp examination can be helpful. If there is histological evidence of disease in these areas, brain biopsy can sometimes be avoided. It is important to ensure that the patient’s HIV status is established if lymphoma is suspected.

The patients need to be staged to asses extent of disease, and to ensure that it is confined to the CNS. This should involve examination, along with staging CT chest/abdo/pelvis. MRI spine and ophthalmology assessment with slit lamp. Bone marrow and testicular u/s. PET ct can also be considered as a staging modality and may detect occult extra CNS disease.

Steroids may be needed for symptoms due to oedema, if possible, where CNS lymphoma is suspected, an urgent biopsy should be done prior, to ensure a diagnostic sample.

In terms of treatment, patient’s comorbidities and performance status will help guide treatment options. Chemotherapy needs to be able to penetrate the blood brain barrier. If the patient is fit enough treatment is usually with high dose methotrexate at 3G/m2 or greater. Addition of other CNS penetrating chemotherapy agents eg high dose cytarabine has been found to improve response rates. 

A recent study (international randomised phase 2 ELSG #32) also shown that the addition of rituximab to HD methotrexate and cytarabine improves complete response rates and improved 5 year failure free survival rates compared to HD methotrexate and cytarabine alone. These results are further improved by the addition of thiotepa to HD methotrexate, cytarabine and rituximab.

Treatment should be given for 4-6 cycles, at 2-3 week intervals.

Autologous stem cell transplants using thiotepa conditioning regimes have also been shown to improve survival.

Whole brain radiotherapy can also be used as consolidation following chemotherapy. The use of this should depend on response to treatment and discussion with patient of benefits vs risks of neurotoxicity should be discussed with the patient. 

Following treatment patients should be followed up. CNS and non CNS relapses can occur, and patients should be monitored for neurocognitive change.

In the relapse setting treatment should be guided by performance status, the site of disease relapse and previous treatments. In patients who have previously responded to methotrexate this can be considered again. Autologous transplant can also be considered.

Do you have any questions? Would you have done anything differently. How does this compare to practice in your local centre?

About TeamHaem

Online education and discussion about all things haematological
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