Bing-Neel Syndrome, a Rare Presentation of Waldenström Macroglobulinemia—A Multicenter Report by the Polish Lymphoma Research Group

Abstract

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014–2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2–32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.

Bing–Neel syndrome, a rare manifestation of WM; a case report and review of literature

“…Three years of overall survival was 47%. 15 In this paper, we reported a middle-aged man with WM and CNS involvement that was responded well to highdose methotrexate and Bendamustine plus Rituximab yet. In this case, the serum IgM was higher than expected value in case of BNS; however, due to brain parenchymal involvement and also massive vasogenic edema, we decided to treat this case as same as BNS.…”

“…The median survival was 28 months, and the 24‐month overall survival was 60%. Three years of overall survival was 47% 15 …”

“… 14 The treatment strategy for BNS is not clearly determined; however, based on previous experience in the treatment of lymphomatous involvement of the central nervous system, we use the same treatment approaches such as high‐dose methotrexate or Cytarabine, because of potential CSF penetration. 15 Alkylating agents such as Bendamustine or nucleoside analogous such as Fludarabine or Cladirabine, have been found to be active, but they have negative impact on marrow cells. 3 New reports on the efficacy of Ibrutinib in the primary management of BNS have been published, and this agent could prolong event‐free survival (EFS) and also overall survival (OS).…”

“…The goal of therapy in WM as an indolent lymphoma is to prolong progression‐free survival (PFS), so BNS can be treated like WM and complete eradication is not feasible or mandatory 14 . The treatment strategy for BNS is not clearly determined; however, based on previous experience in the treatment of lymphomatous involvement of the central nervous system, we use the same treatment approaches such as high‐dose methotrexate or Cytarabine, because of potential CSF penetration 15 . Alkylating agents such as Bendamustine or nucleoside analogous such as Fludarabine or Cladirabine, have been found to be active, but they have negative impact on marrow cells 3 .…”

Waldenstrom Macroglobulinemia Recurrence with Bing–Neel Syndrome Presentation

“…BNS presents a difficult diagnosis due to the rarity of the syndrome and the variety of clinical signs and symptoms. In addition, some symptoms of WM may be related to symptoms observed in other complications like hyperviscosity syndrome or anti-myelin associated glycoprotein (MAG) antibody-related neuropathy [6,7]. BNS may occur at any stage of WM disease, which makes diagnosis even more difficult.…”