Management of central nervous system involvement in chronic lymphocytic leukaemia: a retrospective cohort of 30 patients

Abstract

SummaryCentral nervous system involvement (CNSi) is a rare and poorly reported complication of chronic lymphocytic leukaemia (CLL). Establishing cause and effect between the CLL and the neurological symptoms remains challenging. We have analysed a retrospective cohort of 30 CLL patients with CNSi, documented by lymphocytic infiltration either by flow cytometry of the cerebrospinal fluid (CSF; n = 29) or CNS biopsy (n = 1). Neurological symptoms were heterogeneous. At the time of CNSi, less than half of the patients had a progressive CLL and 20 had never been treated for CLL. Initial treatment with fludarabine-based immuno-chemotherapy, with or without intra-CSF therapy, led to durable response in eight out of nine untreated patients. In contrast, 50% patients receiving various prior treatments needed additional therapy within a median of 4 months (1-16). Ibrutinib led to complete response in 4/4 heavily pre-treated patients. From CNSi, 5-year overall survival was 72% and 48% for treatment-na€ ıve and previously treated patients respectively (P = 0Á06); 5-year progression-free survival (PFS) was 43% and 0% (P = 0Á125). 17p deletion was significantly associated with poor PFS (P = 0Á006). CNSi may be the only sign of progression of CLL and should be considered an initiation criterion of systemic treatment. Prognosis seemed to be related to CLL characteristics rather than to CNSi itself.

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

“…Similar to our results, Strati et al recently described an overall survival of 12 months for patients with CLL with clinically significant CNS involvement . It is interesting that the recent 30‐patient case series by Wanquet et al reported a 5‐year OS of 72%, substantially higher than our data . As the authors note in their study, this may be explained by the fact that a large portion (67%) of their patients were treatment naive, but another explanation is that newer therapies that have displaced older approaches have better response rates.…”

“…Several prior reviews of the literature on leptomeningeal CLL have been published , and more recently, there have been several case series, including a 30‐patient series that is the largest in the literature . We present a case recently encountered in our clinic and undertake a detailed review of the 106 cases, with an emphasis on neurologic presentation, significance of CSF clearance, and clinical response to treatment.…”

How we manage Bing–Neel syndrome

“…Mounting data have suggested clinical efficacy of the oral Bruton Tyrosine Kinase (BTK) inhibitor, ibrutinib, in patients with CLL and mantle cell lymphoma involving the CNS, as well as in patients with primary CNS lymphoma (Bernard et al , ; Chamoun et al , ; Wanquet et al , ). Ibrutinib was also shown to be effective in BNS patients, based on early reports (Cabannes‐Hamy et al , ; Castillo et al , ).…”

Venetoclax with high‐dose methotrexate and rituximab seem effective and well‐tolerated in the treatment of central nervous system involvement of chronic lymphocytic leukemia: A case report

“…Chronic lymphocytic leukemia (CLL) with central nervous system (CNS) involvement is a rare and severe condition . There is currently no consensus regarding optimal management . Venetoclax, an oral BCL‐2 inhibitor, has recently proven to be effective for refractory/relapsed CLL when administered with or without rituximab .…”

“…1,2 There is currently no consensus regarding optimal management. 3,4 Venetoclax, an oral BCL-2 inhibitor, has recently proven to be effective for refractory/relapsed CLL when administered with or without rituximab. 5,6 Venetoclax is a small molecule which is also able to cross the blood-brain barrier as reported in a recent case study demonstrating its clinical and radiological efficacy in a patient with CNS involvement.…”