Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma

Abstract

Overexpression of bcl‐2 and c‐myc are defining features of double‐expressor‐lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c‐myc and bcl‐2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first‐line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5‐fold and 13‐fold higher 5‐year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN‐IPI. DEL improved the discriminatory capability of the NCCN‐IPI ( P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN‐IPI significantly improved the score's discriminatory potential both toward progression‐free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple‐to‐use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN‐IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy.

Vinorelbine as substitute for vincristine in patients with diffuse large B cell lymphoma and vincristine-induced neuropathy

“…Patients treated within the Salzburg cohort met the same inclusion criteria, but dosage of vincristine and doxorubicin was adapted according to adverse events (Supplementary Table 1). Data on baseline characteristics and clinical outcomes were ascertained from our in-house electronic healthcare database system, as previously described [21,22]. The research project was approved by the local institutional review boards (EK-Votum: 32-306 ex19/20 ethikkommission@medunigraz.at and EK-Votum: 415-EP/73/ 127-2012 ethikkommission@salzburg.gv.at).…”

Prognostic Role of Blood Markers in Primary Central Nervous System Lymphoma Patients Treated With High-Dose Methotrexate-Based Therapy

“…Five binary clinical variables, namely, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), lactate dehydrogenase (LDH), cerebrospinal fluid (CSF) protein concentration, and deep brain involvement, were used to distinguish three risk groups in IELSG ( 8 ). As CSF protein data are frequently lacking in clinical practice, it is difficult to perform the IELSG score for prognosis and verify its predictive power ( 3 , 9 , 10 ). In the MSKCC score, Karnofsky performance status (KPS) ≥ 70 and age ≥ 50 years were used as two prognostic factors dividing patients into three risk groups ( 11 ).…”

Primary central nervous system lymphomas express immunohistochemical factors of autophagy

“…Baseline immunohistochemical features with prognostic features according to previous studies were also recorded: The immunohistochemical classification scheme developed by Hans et al for systemic DLBCL subdividing tumors into germinal center B-cell-like (GCB) and non-germinal-center-like (ABC-activated B cell) based on the expression patterns for CD10, BCL6, and MUM1 was used 9 . BCL2 and MYC expression levels (double co-expressors were defined by BCL2 ≥ 70% and MYC ≥ 30% of tumor cells 10 ) were also assessed due to their prognostic significance in this tumor type 10 , 11 . Similarly, given the importance of the immune microenvironment in PCNSLs 12 , PD-L1 (22C3, Dako Agilent) and CD8 expression were analyzed: the percentage of PD-L1 membranous staining of tumor cells and the percentage of CD8 tumor-infiltrating lymphocytes were recorded 13 .…”