A Single Institution Experience of Treating Patients with High Dose Methotrexate for Primary CNS Lymphoma and with Secondary CNS Involvement
Authors: Lalani Tanya L , Staton Ashley D. , Dalovisio Andrew P. , Finn Laura E. , Badari Ambuga , Davis Carter Thomas 
Published: November 2020

Primary CNS lymphoma is a rare condition, with annual incidence of about 1400 cases in the US. Patients with aggressive systemic lymphomas also have high incidence of CNS involvement, with poor overall prognosis. Use of high dose methotrexate based therapies has substantially altered the outlook for these patients.
We present the outcomes data of patients with primary CNS lymphoma and those with secondary CNS involvement treated with high dose methotrexate from a single , FACT accredited academic transplant center.
We reviewed patients treated at our center over a 42 month period between Jan 2017- June 2020.
There were 19 patients with primary CNS lymphoma and 24 with secondary CNS involvement who received high dose methotrexate.
There were equal number of men and women, and were mostly Caucasian. Median age at diagnosis was 60 years. Majority were HIV negative (95%). 3 of the 19 patients had EBV infection at the time of diagnosis. Majority had performance status of ECOG 1 (range: 0-4). 1 patient had CNS lymphoma in the post transplant setting (had bilateral lung transplant). 2 out of 19 patients had concurrent solid organ malignancies.
17 patients (90 %) had newly diagnosed primary CNS lymphoma. 2 patients (10 %) had relapsed disease.
Patients received a median of 6 induction treatments (range 1-12) .
Majority of patients (17/19) received high dose methotrexate with rituximab. 1 patient received only high dose methotrexate. 1 patient received methotrexate, procarbazine, rituximab and vincristine (R MPV).
5 patients (26%) progressed during induction. There were 7 deaths (37 %) during induction phase. Majority of the deaths occured early during induction.
Majority had partial response. 1 patient had complete response . No patient has received stem cell transplant.
There were no chemotherapy delays due to COVID 19 . No patient with primary CNS lymphoma was hospitalized or died due to COVID 19. 1 patient elected to defer chemotherapy due to fear of contracting COVID 19 in the hospital.
No patient received the full,planned doses of high dose methotrexate during induction. Dose reductions were due to poor performance status or impaired renal function.
Consolidation was mainly with high dose methotrexate. Those progressing received whole brain radiation, Ara C , or best supportive care.
The PFS and OS are being evaluated at the time of this submission.
There were 24 patients with secondary CNS involvement . 12 had concurrent systemic and CNS involvement. 12 patients had history of systemic lymphoma but with CNS only relapse. There were equal males and females. Median age at diagnosis was 64 years. (range 33-81). They had good performance status, with majority having PS of ECOG 1 (range 1-3). Majority were caucasian.
There were 4 patients (17%) with EBV infection. 2 patients (8 %) had HIV.
They received a median of 2 high dose methotrexate inductions (range: 1-10). 4 patients (17%) eventually received stem cell transplants.
PFS, survival data are being evaluated at the time of this submission.
In general, high dose methotrexate was well tolerated in both primary CNS lymphoma and systemic lymphoma with CNS involvement. Stem cell transplants are still being done infrequently for these patients.

Disclosures
Finn: Jazz Pharmaceuticals:Speakers Bureau;Celgene:Speakers Bureau;Seattle Genetics:Speakers Bureau.