Primary CNS lymphoma
1% of all non Hodgkin lymphomas, 3 % of all brain tumours. It may [resent with a range of symptoms including focal motor deficits and behavioural change as seen in the patient in this case.
Investigations should include:
- Bloods – FBC/U&ES/LFTS/LDH/PARAPROTEIN/BLOOD FILM/HEPATITIS/HIV
- Contrast enhanced MRI – brain and spine
- Slit lamp exam and ophthalmology review – if necessary vitreous biopsy
- Stereotactic brain biopsy is recommended for histological diagnosis
- PET – CT – to determine systemic involvement.
- Bone marrow not essential if PET excludes systemic disease, normal FBC and no evidence of monoclonal paraprotein
- Testicular ultrasound (testicular involvement cannot be excluded on PET)
- Performance status
- CSF examination – cytology and flow. IGH rearrangments by PCR may improve diagnostic yield
- neuropsychological assessment
- LVEF assessment
- Baseline MMSE
Steroids had already been administered to the patient in our case. Steroids can have a substantial negative impact on yielding diagnosis and therefore should be avoided if possible prior to biopsy. Non‐diagnostic rates range from 33% after a short course (<1 week) to 57% after a longer course of steroid. If steroids have already been given, repeating the MRI to determine if the lesion is still visible is essential following discontinuation of steroids. If no lesion is visible, close monitoring/imaging is essential in these patients until biopsy is possible.
Up to 20% of primary CNS lymphomas have intraocular involvement, which can be difficult to establish. Slit lamp exam and opthalmoscopy are essential followed by vitreous biopsy if necessary. Intravitreal chemotherapy is not routinely recommended in patients who are fit for HD-MTX based regime, but could be consider for patients who are not fit for this treatment and who have isolated intraocular disease.
The gentleman’s performance status was 2 at presentation, however his family inform you he was working full time prior to the Christmas holidays, suggesting a performance status of 0 prior to the onset of symptoms of lymphoma. He was also reasonably fit, undertaking moderate exercise once or twice a week. Performance status is frequently impaired due to the nature of disease, therefore decision for treatment should be based on physiological fitness. Our patient was discussed at MDT and as many have suggested, he is treated with intensive chemotherapy.
Treatment approach should be considered in two stages
- Remission induction
- Consolidation (radiotherapy or autologous stem cell transplant)
For the patient the approach of choice would be intensive methotrexate based induction immunochemotherapy. MATRIX was a regime suggested by most of our followers and most commonly used in the UK. MATRIX has a clear overall survival benefit over HD-MTX/cytarabine regime
MATRIX – HD MTX, cytarabine, thiotepa and rituximab. MTX should be delivered at doses of at least 3g/m2 with an infusion time of 2-4 hours. This is due penetration of the CNS being influenced by the total dose and the rate of infusion – this rapid infusion maximises the therapeutic CSF concentrations. The additional benefit of intrathecal chemotherapy is unknown, given risks of the procedure and low level of evidence, guidelines suggest intrathecal chemotherapy should not be undertaken.
Treatment related mortality associated with MATRIX is 4-7%. Treatment related deaths more commonly occur in the first cycle. Supportive treatment for this regime should include GCSF, PCP and herpes simplex prophylaxis. As our patient suffered with a serious infection following cycle 1, it is important to reassess the chemotherapy plan prior to the second cycle. Guidelines suggest reducing the dose of cytarabine and thiotepa by 25%
Clinicians should aim for this to be undertaken within 6-8 weeks from the first day of the final induction chemotherapy.
Patients who had recieved tiotepa based chemotherapy regime and have achieved at least stable disease should be considered for autologous stem cell transplant. BEAM should not be used as conditioning for transplant, due to previous trials showing poor outcomes. Stem cell collection can be undertaken following cycle 1 or 2
Our patient completed 4 cycles of chemotherapy and ASCT. Follow should include a response assessment at 1-2 months, then MRI every 3-4 months for up to 2 years.
Unfortunately we discovered he had relapsed shortly after treatment. Perhaps we will cover this in a future case!