Leptomeningeal Carcinomatosis in Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature

Abstract

Leptomeningeal disease is a rare complication of chronic lymphocytic leukemia (CLL). We report a case of leptomeningeal disease in CLL with a complete clinical response and clearance of cerebral spinal fluid (CSF) after treatment with ibrutinib and intrathecal rituximab. In a comprehensive review of the published literature since 1976, we found 136 cases of CLL with leptomeningeal spread. We found that leptomeningeal disease in patients with CLL responds favorably to treatment in most cases and is associated with longer overall survival than is expected for other cancers. Clearance of CSF is associated with improved survival. Treatment with rituximab and ibrutinib is more frequently associated with complete response compared with older agents. Implications for Practice The incidence of leptomeningeal CLL is more common than previously described and can be recognized by attention to certain symptoms and signs. This case presentation and literature review reveals that, in many cases, leptomeningeal lymphomatosis is reversible with the use of rituximab and ibrutinib. The authors show a survival benefit associated with treating to cerebral spinal fluid (CSF) clearance by cytology and compare outcomes with various treatment strategies, focusing on novel agents. Now that there is effective therapy for leptomeningeal lymphoma in CLL, the importance for oncologists to recognize this neurologic complication has become clear.

Neurology Case Report: Rapidly Progressive Dementia and Extrapyramidal Symptoms as the First Presentation of Leptomeningeal Carcinomatosis

“…However, Naydenov and Taylor hypothesize that symptoms are not heterogeneous but rather a result of one or a combination of an increase in the intracranial pressure, parenchymal irritation associated with inflammatory cytokines, and clumping at the rootlets [ 15 ]. They found that 99% of patients fall into one of these categories, and our patient falls under many of these categories [ 15 ].…”

“…However, Naydenov and Taylor hypothesize that symptoms are not heterogeneous but rather a result of one or a combination of an increase in the intracranial pressure, parenchymal irritation associated with inflammatory cytokines, and clumping at the rootlets [ 15 ]. They found that 99% of patients fall into one of these categories, and our patient falls under many of these categories [ 15 ]. As a result of this disease, patients complain of general symptoms such as altered mental status, back pain, nausea and vomiting, cerebellar signs, diplopia, leg weakness, and most commonly headache [ 7 ].…”

Kesintasan Pasien Dengan Metastasis Leptomeningeal Yang Dirawat Di Bagian Neurologi Rumah Sakit Kanker Dharmais Dan Rsupn DR Cipto Mangunkusumo

“…Naydenov dan Taylor melaporkan overall survival rate pada chonic lymphocytic leukemia lebih dari 9 bulan dan mencapai lebih dari 10 bulan sejak meningkatnya penggunaan rituximab dan ibrutinib. 4,5 Diagnosis ML sulit ditegakkan, meskipun secara klinis sangat mencurigakan. ML ini seringkali dijumpai pada stadium lanjut proses keganasan.…”

“…Terjadi berkisar 5% sampai 8% pada tumor solid dan 5% sampai 15% pada keganasan hematologik. 5,10,12 Pemeriksaan penunjang yang dilakukan berupa MRI kepala atau spine menunjukkan 84,7% ada lesi leptomeningeal dan pemeriksaan CSS. Penelitian yang dilakukan Pan dkk mendapatkan 90% pasien memperlihatkan hasil neuroimaging yang sesuai dengan ML.…”

“…Dalam satu serial pasien, dilaporkan bahwa keganasan hematologik memiliki kesintasan yang sedikit lebih baik dibandingkan tumor solid yaitu 4,7 bulan dibandingkan 2,3 bulan. 5,11 ML yang berasal dari tumor solid mempunyai angka kematian yang tinggi dalam 4 sampai 6 minggu jika tidak diterapi. Hal ini dapat disebabkan karena tumor solid sering menginfiltrasi dasar otak, fissure Silvius, adanya reaksi fibrosis reaktif dan in amasi yang dapat menghambat aliran CSS dan menyebabkan terjadinya hidrosefalus dan peningkatan tekanan intrakranial sehingga seringkali cepat menyebabkan kematian.…”