Complete Response to Temozolomide Treatment in an Elderly Patient With Recurrent Primary Central Nervous System Lymphoma-Case Report-

Makino, Keishi; Nakamura, Hideo; Kudo, Mareina; Takeshima, Hideo; Kuratsu, Jun Ichi

doi:10.2176/nmc.47.229

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…Bruton tyrosine kinase inhibitor ibrutinib was introduced as a novel effective agent to PCNSL, especially to B-cell type lymphoma. 24) Temozolomide (TMZ) treatment or immunotherapy might be one of the selections for lymphomatosis cerebri as an adjuvant treatment following MTX therapy, 15,[25][26][27] although the effect of TMZ on PCNSL has not yet been proven. When an effective treatment for lymphomatosis cerebri is established, improvement of the patient's cognitive function can be expected.…”

Section: Discussionmentioning

confidence: 99%

A Case of Lymphomatosis Cerebri Presenting with Rapid Progression of Dementia: A Literature Review

Yamada

Tomita

Takahashi

et al. 2022

NMC Case Report Journal

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Lymphomatosis cerebri is an atypical form of primary central nervous system lymphoma (PCNSL), which frequently causes rapid progression of dementia. A 68-year-old woman exhibited rapidly progressing disorientation and a mini-mental state examination score of 9. The fluid-attenuated inversion recovery of a magnetic resonance image (MRI) demonstrated focal areas of high-signal intensity in the right frontal lobe with a small enhancement, which was histologically diagnosed as diffuse large B-cell type lymphoma. The lesion dramatically shrank, and no enhancements were identified on MRI after treatment with high-dose methotrexate (MTX) and whole-brain radiation (WBR). However, her recovery of cognitive function was poor. The patient visited our clinic every 2 months but succumbed to systemic mycotic sepsis 14 months after the biopsy. Autopsy revealed lymphomatosis cerebri in the patient based on a feature of scattered small clusters of lymphoma cells infiltrating into the brain parenchyma in both cerebral hemispheres. Differentiation of lymphomatosis cerebri from other white matter degenerative diseases is usually challenging because lymphomatosis cerebri seldom forms mass lesions. In lymphomatosis cerebri, the lymphoma cells infiltrate into several regions in the brain tissue, including the basal ganglia, brainstem, and corpus callosum, in addition to periventricular and subcortical white matters. The rapid deterioration of cognitive function in the patient suggests a rapid spread of lymphomatosis cerebri, necessitating early histological diagnosis and prompt treatments. If the diagnosis is obtained, administration of high-dose MTX and WBR followed by rituximab and cytarabine can contribute to a longer survival time, based on our literature review.

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Section: Discussionmentioning

confidence: 99%

A Case of Lymphomatosis Cerebri Presenting with Rapid Progression of Dementia: A Literature Review

Yamada

Tomita

Takahashi

et al. 2022

NMC Case Report Journal

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“…Alkylating agents are generally effective against non-Hodgkin's lymphoma and temozolomide has good CNS penetration and a favorable toxicity profile [9,10]. The use of single-agent temozolomide as salvage therapy for PCNSL has been described in case reports [11][12][13] and a phase II trial assessed the activity of single-agent temozolomide in patients with recurrent PCNSL [14]. These findings suggested that temozolomide as a promising salvage treatment for refractory or relapsed PCNSL.…”

Section: Introductionmentioning

confidence: 99%

Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status

et al. 2011

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High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary central nervous system lymphoma (PCNSL). Because treatment options in patients with progressive or recurrent PCNSL are limited, prognosis is poor. Temozolomide, a well-tolerated oral alkylating agent that permeates the blood brain barrier (BBB), is effective against malignant glioma and recurrent PCNSL. The gene for the deoxyribonucleic acid (DNA) repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), which is closely related to cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation. We evaluated the results of temozolomide treatment and the methylation status of the promoter region of the MGMT gene in 17 patients (median age 68 years) with refractory or relapsed PCNSL. They were immunocompetent and had received initial treatment with HD-MTX (3.5 g/m(2)) with or without irradiation. All were treated with temozolomide 150-200 mg/m(2), for 5 days in the course of 28 days; treatment was continued until disease progression. We observed five complete remissions, five partial responses (PRs) with stable disease (SD), and seven with disease progression. Median overall survival after the temozolomide treatment was 6.7 months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven tumor specimens were available for MGMT analysis. MGMT promoter methylation (mMGMT) in the tumor tissue was found in 4 (36.4%), the other seven harbored a non-methylated MGMT promoter (nmMGMT). There was no statistically significant difference in median overall survival between patients with mMGMT (11.1 months) and nmMGMT (6.7 months) (P = 0.63). Although some patients were elderly and had been heavily pre-treated, temozolomide resulted in a complete response (CR) in 29% and was well tolerated without any major toxicity.

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O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma

et al. 2013

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Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8-52). Five patients with low MGMT level (<30 %) showed a response to temozolomide. Only one of 10 patients (10 %) with high MGMT level (≥30 %) exhibited a response to temozolomide. Small sample numbers precluded formal statistical comparisons. Two patients with complete response remain alive without progressive disease 6.7 and 7.2 years after temozolomide initiation. Immunohistochemistry can be performed on small biopsies to selectively assess MGMT status in tumor versus surrounding inflammation. MGMT analysis by immunohistochemistry may predict response to temozolomide in PCNSL and should be prospectively investigated.

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Complete Response to Temozolomide Treatment in an Elderly Patient With Recurrent Primary Central Nervous System Lymphoma-Case Report-

Cited by 6 publications

References 28 publications

A Case of Lymphomatosis Cerebri Presenting with Rapid Progression of Dementia: A Literature Review

A Case of Lymphomatosis Cerebri Presenting with Rapid Progression of Dementia: A Literature Review

Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status

O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma

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